WorldWideScience

Sample records for brtl osteogenesis imperfecta

  1. What Is Osteogenesis Imperfecta?

    Science.gov (United States)

    ... your browser. Home Osteogenesis Imperfecta Osteogenesis Imperfecta Basics What Is Osteogenesis Imperfecta? Fast Facts: An Easy-to- ... Being Done on Osteogenesis Imperfecta? For More Information What Causes Osteogenesis Imperfecta? OI is caused by one ...

  2. Osteogenesis imperfecta.

    Science.gov (United States)

    Huber, Michaell A

    2007-03-01

    Osteogenesis imperfecta is a relatively common hereditary connective tissue disorder characterized by bone fragility and fractures. Other frequently affected tissues include tendons, ligaments, skin, sclera, teeth, and middle and inner ear. Molecular studies have demonstrated that most cases result from mutations affecting the genes responsible for the formation of type 1 collagen. The phenotypic presentation varies from mild to lethal. Commonly observed dental abnormalities include dentinogenesis imperfecta and malocclusion. Medical therapies using bisphosphonates have resulted in reduced fracture risk and decreased bone pain. To date, no cases of bisphosphonate-associated osteonecrosis have been reported. With appropriate precautions, the patient with osteogenesis imperfecta can tolerate and benefit from the delivery of necessary dental care to control oral disease, improve function, and improve esthetics.

  3. Osteogenesis imperfecta and dentinogenesis imperfecta: associated disorders.

    Science.gov (United States)

    Rios, Daniela; Vieira, Ana Luiza Falavinha; Tenuta, Livia Maria Andaló; Machado, Maria Aparecida de Andrade Moreira

    2005-10-01

    This paper presents a review of dentinogenesis imperfecta occurring in patients with osteogenesis imperfecta. The systemic manifestations and the oral aspects of dentinogenesis imperfecta in osteogenesis imperfecta are discussed, and an illustrative case is described.

  4. Osteogenesis imperfecta.

    Science.gov (United States)

    Brusin, Joyce Helena

    2008-01-01

    "Fragile bones" have been described in medical literature for centuries. Cases dating from antiquity include dental and skeletal details eerily similar to those found among modern patients whose bones fracture easily and whose bodies show signs of muscular and other weakness. Osteogenesis imperfecta--whose name implies "imperfect birth of bone"--is one of these inherited fragile bone syndromes. A generalized disorder of the body's connective tissues, it is most obvious in its effect on bone, but also involves the body's ligaments, tendons, fascia, eyes, skin, teeth and ears. Radiographs, bone scans and other imaging tools are essential in the initial diagnosis, assessment of fracture risk, and planning and tracking of treatment. PMID:18650529

  5. Osteogenesis imperfecta type V

    DEFF Research Database (Denmark)

    Rauch, Frank; Moffatt, Pierre; Cheung, Moira;

    2013-01-01

    Osteogenesis imperfecta (OI) type V is an autosomal dominant bone fragility disorder that we had described a decade ago. Recent research has shown that OI type V is caused by a recurrent c.-14C>T mutation in IFITM5. In the present study, we assessed all patients diagnosed with OI type V at our...

  6. Dentinogenesis imperfecta in adults with osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Gjørup, Hans; Hald, Jannie Dahl; Schmidt, Malene;

    Aims: To describe the prevalence and the clinical variation of dentinogenesis imperfecta (DI) in adults with various types of osteogenesis imperfecta (OI). Methods: A total of 72 patients with a medically confirmed diagnosis of OI were recruited from Aarhus University Hospital, Department...

  7. Osteogenesis imperfecta/lobstein syndrome associated with dentinogenesis imperfecta.

    Science.gov (United States)

    Lingaraju, Naresh; Nagarathna, P J; Vijayalakshmi, R; Sheshadri, P

    2013-01-01

    Osteogenesis imperfecta is a collagen related disorder characterized by increased bone fragility and low bone mass. The important oral finding in osteogenesis imperfect is the presence of dentinogenesis imperfecta. This article presents a case of osteogenesis imperfecta (type IV B) with dentinogenesis imperfecta where a 7-year-old girl had opalacent primary teeth associated with severe bone deformity, scoliosis, barrel shaped rib cage, and short stature. The clinical, radiographic ad histologic features are reviewed along with management aspects.

  8. Osteogenesis imperfecta/lobstein syndrome associated with dentinogenesis imperfecta.

    Science.gov (United States)

    Lingaraju, Naresh; Nagarathna, P J; Vijayalakshmi, R; Sheshadri, P

    2013-01-01

    Osteogenesis imperfecta is a collagen related disorder characterized by increased bone fragility and low bone mass. The important oral finding in osteogenesis imperfect is the presence of dentinogenesis imperfecta. This article presents a case of osteogenesis imperfecta (type IV B) with dentinogenesis imperfecta where a 7-year-old girl had opalacent primary teeth associated with severe bone deformity, scoliosis, barrel shaped rib cage, and short stature. The clinical, radiographic ad histologic features are reviewed along with management aspects. PMID:23579912

  9. Metaphyseal bands in osteogenesis imperfecta

    International Nuclear Information System (INIS)

    An increasing number of patients with osteogenesis imperfecta are undergoing pamidronate therapy to prevent the incidence of fragility fractures. The authors herein report a child aged 3 years who received five cycles of pamidronate, resulting in metaphyseal bands, known as “zebra lines.”

  10. Dentinogenesis imperfecta associated with osteogenesis imperfecta.

    Science.gov (United States)

    Biria, Mina; Abbas, Fatemeh Mashhadi; Mozaffar, Sedighe; Ahmadi, Rahil

    2012-07-01

    This paper presents a case with dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta. Systemic and dental manifestations of OI and its medical and dental treatments are discussed in this paper. A 5-year-old child with the diagnosis of OI was referred to the Dental School of Shaid Beheshti University of Medical Sciences. On clinical examination yellow/brown discoloration of primary teeth with the attrition of the exposed dentin and class III malocclusion was observed. Enamel of first permanent molars was hypoplastic. Radiographic examinations confirmed the diagnosis of DI. A histological study was performed on one of the exfoliating teeth, which showed abnormal dentin. Primary teeth with DI were more severely affected compared to permanent teeth; enamel disintegration occurred in teeth with DI, demonstrating the need for restricts recalls for these patients.

  11. Dentinogenesis imperfecta associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Mina Biria

    2012-01-01

    Full Text Available This paper presents a case with dentinogenesis imperfecta (DI associated with osteogenesis imperfecta. Systemic and dental manifestations of OI and its medical and dental treatments are discussed in this paper. A 5-year-old child with the diagnosis of OI was referred to the Dental School of Shaid Beheshti University of Medical Sciences. On clinical examination yellow/brown discoloration of primary teeth with the attrition of the exposed dentin and class III malocclusion was observed. Enamel of first permanent molars was hypoplastic. Radiographic examinations confirmed the diagnosis of DI. A histological study was performed on one of the exfoliating teeth, which showed abnormal dentin. Primary teeth with DI were more severely affected compared to permanent teeth; enamel disintegration occurred in teeth with DI, demonstrating the need for restricts recalls for these patients.

  12. Osteogenesis imperfecta: pathophysiology and treatment.

    Science.gov (United States)

    Hoyer-Kuhn, Heike; Netzer, Christian; Semler, Oliver

    2015-07-01

    Osteogenesis imperfecta is a rare hereditary disease mostly caused by mutations impairing collagen synthesis and modification. Recently recessive forms have been described influencing differentiation and activity of osteoblasts and osteoclasts. Most prominent signs are fractures due to low traumata and deformities of long bones and vertebrae. Additional patients can be affected by dwarfism, scoliosis Dentinogenesis imperfecta, deafness and a blueish discoloration of the sclera. During childhood state of the art medical treatment are i.v. bisphosphonates to increase bone mass and to reduce fracture rate. Surgical interventions are needed to treat fractures, to correct deformities and should always be accompanied by physiotherapeutic and rehabilitative interventions.

  13. Recent developments in osteogenesis imperfecta

    OpenAIRE

    Joseph L. Shaker; Carolyne Albert; Jessica Fritz; Gerald Harris

    2015-01-01

    Osteogenesis imperfecta (OI) is an uncommon genetic bone disease associated with brittle bones and fractures in children and adults. Although OI is most commonly associated with mutations of the genes for type I collagen, many other genes (some associated with type I collagen processing) have now been identified. The genetics of OI and advances in our understanding of the biomechanical properties of OI bone are reviewed in this article. Treatment includes physiotherapy, fall prevention, and s...

  14. Treatment Concepts of Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Ramji Lal Sahu

    2012-06-01

    Full Text Available Background: To explore the Application of the intramedullary nails for correction of deformity in the lower limbs and decrease the opportunity of refractures in children with osteogenesis imperfecta.Materials and Methods: From July 2005 to July 2009, 11 patients (5 males and 6 females, were recruited from Emergency and outpatient department having deformities of osteogenesis imperfecta in lower limbs. With 3 femurs and 5 tibias with deformity in lower limps were corrected by multiosteotomy and fixed with intramedullary interlocking nails, 6 (3 femurs and 3 tibias for Rush nails; 6 (2 femurs and 4 tibias for Ender nails; and 12 (6 femurs and 6 tibias for flexible intramedullary nails. All patients were operated under general or spinal anesthesia. Results: All deformities were perfectly corrected. All patients were available at final follow up, for 9 months to 36 months, mean 18 months. 2 patients had delayed union, 2 had superficial infection in the incision or pin tract, and 1 had refractures postoperatively. The results were excellent in 72.727% and good in 27.272% patients. Conclusion: Multiosteotomy and fixed intramedullary nails can correct the deformity in the lower limbs perfectly and decrease the opportunity of refractures in children with osteogenesis imperfecta, which has been proved to be a reliable method.

  15. Osteogenesis Imperfecta in Pregnancy: Case Report

    Directory of Open Access Journals (Sweden)

    Maryam Rabiee

    2011-03-01

    Full Text Available Osteogenesis imperfecta is a rare inherited Connective tissue disorder with an expression that varies from mild to severe disease affecting bone, Sclera and middle ear. Fertility is preserved, especially in those patients with type 1. We present hereby a pregnant woman with Osteogenesis imperfecta that had over 30 fractures in long bones and vertebrae. The object of this report was to determine choice of delivery method, maternal and neonatal Complications and prenatal diagnosis.

  16. Osteogenesis imperfecta in childhood : Prognosis for walking

    NARCIS (Netherlands)

    Engelbert, RHH; Uiterwaal, CSPM; Gulmans, VAM; Pruijs, H; Helders, PJM

    2000-01-01

    Objectives: We studied the predicted value of disease-related characteristics for the ability of children with osteogenesis imperfecta (OI) to walk. Study design: The severity of OI was classified according to Sillence. The parents were asked to report the age at which the child achieved motor miles

  17. Dentinogenesis imperfecta associated with osteogenesis imperfecta: report of two cases.

    Science.gov (United States)

    Tsai, Chia-Ling; Lin, Yng-Tzer; Lin, Yai-Tin

    2003-02-01

    Osteogenesis imperfecta (OI) is a heritable systemic disorder of the connective tissue. Dentinogenesis imperfecta (DI), which is sometimes an accompanying symptom of OI, belongs to a group of genetically conditioned dentin dysplasias and is characterized clinically by an opalescent amber appearance of the dentin. Although the teeth of DI cases wear more easily and excessively compared to normal teeth, they do not appear to be more susceptible to dental caries than normal teeth. Two cases of DI associated with OI are presented in this paper, with 1 case suffering from nursing bottle caries. The purposes of this paper are to present the dental and skeletal characteristics of moderately and mildly involved DI associated with OI, and to discuss the possible methods of dental treatment. Patients with OI and opalescent teeth should be evaluated as soon as the deciduous teeth erupt; immediate dental involvement and oral hygiene instruction can be of help in reducing the necessity of extensive dental care.

  18. Le cas clinique du mois. Osteogenesis imperfecta

    OpenAIRE

    Kaux, Jean-François; Le Goff, Caroline; Debray, François-Guillaume; Crielaard, Jean-Michel; Reginster, Jean-Yves

    2009-01-01

    We report the case of a young boy who had had multiple bone fractures (more than 10) since the age of 19 months. The father had the same clinical history. The clinical examination was normal for his age except blue sclera. The bone densitometry showed a severe osteoporosis for his age. Biological exam swere correct. The genetic exploration revealed mutation of COL1A2 gene. With this clinical history, the diagnosis of Osteogenesis imperfecta (OI) was retained. OI is a hereditary dystrophy with...

  19. The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Babak Soltani

    2011-09-01

    Full Text Available ObjectiveA 4-month-old female with osteogenesis imperfecta (OI type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA type I was diagnosed.Keywords: Osteogenesis imperfecta; spinal muscular atrophy; hypotonia

  20. The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

    OpenAIRE

    Babak Soltani; Abdollah Karimi; Alireza Fahimzad; Mahshid Talebian

    2011-01-01

    ObjectiveA 4-month-old female with osteogenesis imperfecta (OI) type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA) type I was diagnosed.Keywords: Osteogenesis imperfecta; spinal muscular atrophy; hypotonia

  1. [Genetic heterogeneity of osteogenesis imperfecta. Study of 6 cases].

    Science.gov (United States)

    Olivares, J L; Hernández, M C; Bueno, M

    1986-09-01

    Osteogenesis imperfecta one of the most common disorders of connective tissue, has been known for centuries. The most characteristic alterations which define it are: osteoporosis, osseous fragility with multiple fractures, blue sclerae, deafness and imperfect dentinogenesis. Important advances in the biochemical, anatomopathological, genetic, therapeutic and prophylactic fields have resulted in a great present-day interest in this disease. In this work we report six cases of osteogenesis imperfecta according to the current classification and we review the most outstanding aspects. PMID:3789548

  2. Osteogenesis Imperfecta:No Place for Imperfect Anaesthesiologist

    Directory of Open Access Journals (Sweden)

    Geeta Bhandari

    2008-01-01

    Full Text Available Osteogenesis imperfecta, an inherited disease of connective tissue, is associated with anatomic and physiologic abnormalities which make any form of anaesthesia a challenging task for the anaesthesiologist. We report a case of Osteogenesis imperfecta type -IV with severe anatomic deformities, who underwent replacement nailing procedure for periprosthetic fracture of shaft femur under general anaesthesia. We used a proseal LMA in the case, patient suffered a posterior dislocation of right shoulder on repositioning at the end of the surgery.

  3. Osteogenesis Imperfecta:No Place for Imperfect Anaesthesiologist

    OpenAIRE

    Geeta Bhandari; K S Shahi; Poonam Bhadoria; Anju R Bhalotra; O D Sandhya; Mona Arya

    2008-01-01

    Osteogenesis imperfecta, an inherited disease of connective tissue, is associated with anatomic and physiologic abnormalities which make any form of anaesthesia a challenging task for the anaesthesiologist. We report a case of Osteogenesis imperfecta type -IV with severe anatomic deformities, who underwent replacement nailing procedure for periprosthetic fracture of shaft femur under general anaesthesia. We used a proseal LMA in the case, patient suffered a posterior dislocation of right shou...

  4. Assessment of dysplastic dentin in osteogenesis imperfecta and dentinogenesis imperfecta.

    Science.gov (United States)

    Malmgren, Barbro; Lindskog, Sven

    2003-04-01

    Two semiquantitative scoring systems, Clinical Radiographic Score (CRS) and Dysplastic Dentin Score (DDS), were introduced for analyzing degree of dysplastic manifestations in dentin. The utility of both systems was demonstrated in a large material of teeth from patients with dentinogenesis imperfecta (DI) and osteogenesis imperfecta (OI). Twenty teeth from healthy controls, 81 teeth from 40 patients with OI, and 18 teeth with DI without OI (DI type II) were examined. The degree of dysplasia was correlated with type and form of OI and type of DI. The median DDS did not differ between DI associated with OI (DI type I) and DI type II. DDS in OI patients without clinical signs of DI was above that of control teeth. Both circumpulpal and mantle dentin showed increased DDS, although circumpulpal dentin was more severely affected. The median DDS was highest for the most severe type of non-lethal OI (type III). DDS increased significantly with form (severity) of OI. A significant association between DDS and CRS was found, although diagnosis of DI in less severe cases was not possible based on radiographic or clinical signs alone. Thus, the DDS system proved valuable when the CRS system based on radiographic/clinical manifestations failed, the most significant finding being subclinical histological manifestations of DI in patients with OI but without clinical or radiographic signs of DI. These subtle dysplastic changes are most likely an expression of genetic disturbances associated with OI and should not be diagnosed as DI, but rather be termed histologic manifestations of dysplastic dentin associated with OI.

  5. Orthodontic and orthognathic management of a patient with osteogenesis imperfecta and dentinogenesis imperfecta: a case report.

    Science.gov (United States)

    Kindelan, J; Tobin, M; Roberts-Harry, D; Loukota, R A

    2003-12-01

    This case report describes a patient's severe Class III malocclusion, managed with a combination of orthodontic and orthognathic treatment. The medical history was complicated by osteogenesis imperfecta and dentinogenesis imperfecta. In addition the patient was a Jehovah's Witness. Patients with osteogenesis imperfecta carry an increased risk of perioperative haemorrhage, and this led to bimaxillary surgery being carried out as two discrete surgical episodes for the patient described. In addition, the risk of enamel fracture led to orthodontic bands being cemented on all teeth. In spite of the increased risks a successful outcome was achieved.

  6. Prenatal diagnosis of lethal osteogenesis imperfecta in twin pregnancy.

    Science.gov (United States)

    Morin, L R; Herlicoviez, M; Loisel, J C; Jacob, B; Feuilly, C; Stanescu, V

    1991-06-01

    Lethal osteogenesis imperfecta was diagnosed at 27 weeks amenorrea in one fetus of a bichorial twin pregnancy. Sonographic findings included: short-limb dwarfism, hypotrophy and hypoechoic bones. The affected fetus was so translucent that only the normal fetus could be seen on plain in utero radiography. The affected fetus died immediately after birth. Postmortem radiography and histology were typical of lethal osteogenesis imperfecta of type IIA. Aids to the etiological diagnosis of in utero dwarfism are presented. Sonographic features correlated with neonatal death are described. PMID:1863995

  7. Pseudomass of the sternal manubrium in osteogenesis imperfecta

    International Nuclear Information System (INIS)

    Skeletal abnormalities such as hypertrophic callus formation and ''popcorn'' calcifications are rare radiological findings of osteogenesis imperfecta, causing tumor-like appearances on imaging. We report on a 7-year-old girl with osteogenesis imperfecta presenting with hepatomegaly and palpable lymphadenopathy in the left inguinal region on physical examination. Computed tomography examination revealed a high-density mass-like lesion of the manubrium sterni. Ultrasonography and a lateral roentgenogram of the chest verified that this was a pseudomass caused by a bowed sternal manubrium. (orig.)

  8. A CASE OF OSTEOGENESIS IMPERFECTA WITH S IGNIFICANT DISABILITY

    OpenAIRE

    Sahana; Adarsh; Rajanish; Nirmala; Sreekrishna

    2014-01-01

    Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by structural and quantitative defects in type 1 collagen resulting in susceptibility to fractures of long bones or vertebral compressions from mild or inconsequential trauma 1 .There are different types that range in seve rity from mild form to perinatal lethal form. We present a case of type 3 osteogenesis imperfect with multiple fractures , severe short stature and severe d...

  9. A CASE OF OSTEOGENESIS IMPERFECTA WITH S IGNIFICANT DISABILITY

    Directory of Open Access Journals (Sweden)

    Sahana

    2014-01-01

    Full Text Available Osteogenesis imperfecta (OI is a rare genetic disorder characterized by structural and quantitative defects in type 1 collagen resulting in susceptibility to fractures of long bones or vertebral compressions from mild or inconsequential trauma 1 .There are different types that range in seve rity from mild form to perinatal lethal form. We present a case of type 3 osteogenesis imperfect with multiple fractures , severe short stature and severe disability who survived till 5 years of age.

  10. A rare case of Osteogenesis Imperfecta Type III

    Directory of Open Access Journals (Sweden)

    Nagaraj MV, Jehangir HM

    2014-03-01

    Full Text Available Osteogenesis imperfecta (OI the most common genetic cause of osteoporosis is a generalized disorder of connective tissue, characterized by increased bone fragility, low bone mass, recurrent fractures & numerous extra-osseous features with unusual presentations. We report a case of 7 year old female child presenting with respiratory distress with bowing of limb. This case is presented for its rarity.

  11. Osteogenesis imperfecta: the audiological phenotype lacks correlation with the genotype.

    NARCIS (Netherlands)

    Swinnen, F.K.R.; Coucke, P.J.; Paepe, A.M. De; Symoens, S.; Malfait, F.; Gentile, F.V.; Sangiorgi, L.; D'Eufemia, P.; Celli, M.; Garretsen, T.J.; Cremers, C.W.R.J.; Dhooge, I.J.; Leenheer, E. de

    2011-01-01

    ABSTRACT: BACKGROUND: Osteogenesis Imperfecta (OI) is a heritable connective tissue disorder mainly caused by mutations in the genes COL1A1 and COL1A2 and is associated with hearing loss in approximately half of the cases. The hearing impairment usually starts between the second and fourth decade of

  12. The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Babak Soltani

    2011-06-01

    Full Text Available ObjectiveA 4-month-old female with osteogenesis imperfecta (OI type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA type I was diagnosed.

  13. Radiation therapy of hyperplastic heterotopic ossifications in osteogenesis imperfecta

    International Nuclear Information System (INIS)

    Purpose: Osteogenesis imperfecta is a rare hereditary disease of connective tissue with a genetic defect in collagen synthesis. In osteogenesis imperfecta hyperplastic heterotopic ossification can be induced by hyperplastic callus formation caused by trauma or operation. Heterotopic ossifications can be found in numerous benign diseases. The successful use of low dose radiotherapy in the treatment of heterotopic ossifications in well-known from the literature. Patients and Methods: We treated two children (a 13-year old girl and a ten-year old boy) with heterotopic ossifications of the lower extremities in osteogenesis imperfecta type IV (Lobstein) with a low dose irradiation (10x1 Gy, respectively 6x1 Gy) under megavoltage conditions. Results: After radiotherapy the children were painfree and the hyperplastic callus was considerably reduced. The previously immobilized patients could partly be mobilized. Thereby it could be contributed to the rehabilitation of the patients. New hyperplastic callus formation was not observed in the irradiated areas so far. Conclusion: Analogous to the successful radiation of heterotopic ossifications in other benign diseases radiation therapy seems to be a successful treatment of hyperplastic callus formation in osteogenesis imperfecta. Despite the late risks of radiotherapy radiation treatment of benign diseases in children might be indicated. (orig.)

  14. Phlorotannin-incorporated Mesenchymal Stem Cells and their Promising Role in Osteogenesis Imperfecta

    OpenAIRE

    Tehseen Fatima Ali; Tabinda Hasan

    2012-01-01

    Osteogenesis imperfecta as the name suggests, is a bone disorder characterised by imperfect bone mineralisation and development. The key defect lies in the osteoblast–osteoid cycle, leading to insufficient calcification and consequently weak bones. Osteogenesis imperfecta patients are prone to fractures. Till date, numerous growth hormone/synthetic analogues have been used therapeutically in osteogenesis imperfecta patients and they do provide temporary relief, but not without numerous unwant...

  15. [Osteogenesis imperfecta and dentinogenesis imperfecta: diagnostic frontiers and importance in dentofacial orthopedics].

    Science.gov (United States)

    Kamoun-Goldrat, Agnès S; Le Merrer, Martine F

    2007-06-01

    Osteogenesis imperfecta is a genetic disease that varies in severity and is characterized by fragile bones that fracture easily. Many extra-skeletal manifestations can be noted such as blue sclerotic markings, dentinogenesis imperfecta and impaired hearing or deafness. In most cases, an anomaly of collagen is the cause. It is usually accompanied by a specific Class III type cranio-facial morphology with open bite and increased incidence of impacted permanent molars. Orthodontists called upon to treat the dental aspects of this malady, should be careful to protect their patients against bacterial infection and hemorrhages, and to be well aware of the side affects that can be caused by the biophosphanates that constitute the basis of current medical treatment of osteogenesis imperfecta.

  16. Anesthetic Management in a Gravida with Type IV Osteogenesis Imperfecta

    Science.gov (United States)

    Vue, Elizabeth; Davila, Juan

    2016-01-01

    Osteogenesis imperfecta (OI) is an inherited disorder of the connective tissues caused by abnormalities in collagen formation. OI may present many challenges to the anesthesiologist. A literature review reveals a wide range of implications, from basic positioning to management of the difficult airway. We present the anesthetic management of a 25-year-old gravid woman with OI, fetal demise, and possible uterine rupture, admitted for an exploratory laparotomy.

  17. The quality of genetic counselling in osteogenesis imperfecta.

    OpenAIRE

    Paterson, C R; Mowat, E

    1981-01-01

    A survey is reported of the genetic advice given to 272 families with osteogenesis imperfecta. An appreciable number of families were not given advice by anyone even though they had asked for it, and only one quarter of the families had been referred to a clinical genetic specialist. Overall approximately one third of the information recollected as having been received was incorrect but genetic specialists were clearly more successful than other doctors.

  18. Craniospinal abnormalities and neurologic complications of osteogenesis imperfecta: imaging overview.

    Science.gov (United States)

    Khandanpour, Nader; Connolly, Daniel J A; Raghavan, Ashok; Griffiths, Paul D; Hoggard, Nigel

    2012-01-01

    Osteogenesis imperfecta is a rare genetic disorder that leads to progressive skeletal deformities due to deficits in type I collagen, the main pathophysiologic effect of the disease. In addition, it may lead to a wide range of associated neurologic abnormalities: The central nervous system is usually involved because of softening of bone at the base of the skull, with resultant upward migration of the upper cervical spine and odontoid process into the skull base. Upward migration of the spine may cause compression of the brainstem, mechanical impingement of the spinal canal with restriction of cerebrospinal fluid circulation, and impingement of the cranial nerves. Osteogenesis imperfecta also may directly involve neurovascular structures, leading to cavernous fistulas of the carotid artery, dissection of the cervical arteries, and cerebral aneurysms. The brain parenchyma is frequently affected by the disease, with manifestations including cerebral atrophy, communicating hydrocephalus, and cerebellar hypoplasia. The imaging features of the disorder vary as widely as its clinical manifestations, depending on the severity of disease. Severe forms accompanied by debilitating skeletal fractures and progressive neurologic impairments may lead to perinatal death, whereas milder asymptomatic forms might cause only a modest reduction in life span. The most important advance in medical therapy for osteogenesis imperfecta has been the introduction of bisphosphonate therapy to slow the resorption of bone in patients with moderate to severe forms of the disease (ie, type III or IV). In some patients, neurosurgery may be necessary to correct the effects of severe basilar invagination by the odontoid process. PMID:23150860

  19. Pathophysiology and therapeutic options in osteogenesis imperfecta: an update

    Directory of Open Access Journals (Sweden)

    Brizola E

    2016-03-01

    Full Text Available Evelise Brizola,1 Temis M Félix,2 Jay R Shapiro3 1Bone and Osteogenesis Imperfecta Department, Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA; 2Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Osteoporosis and Metabolic Bone Disorders Center, Bethesda, MD, USAAbstract: Osteogenesis imperfecta (OI is a rare, heritable systemic disorder of bone and connective tissue, which in almost 90% of cases is due to mutations affecting the normal synthesis of type I collagen. In 1979, four OI phenotypes were categorized which were inherited as autosomal dominant characteristics. Individuals with OI present both genetic and phenotypic variabilities. Major characteristics of OI are bone fragility, blue sclerae, dentinogenesis imperfecta, short stature, scoliosis, and joint hyperextensibility. Both autosomal dominant and recessive inheritance are now recognized. Advances in molecular diagnosis have led to a major expansion in our understanding of the genetic basis for different OI phenotypes. To date, sequence variants in 17 genes are described as causative of OI. These genes regulate the synthesis of type I collagen pro-alpha polypeptide chains, proteins involved in type I collagen processing in the endoplasmic reticulum and proteins involved in osteoblast function. These new genetic associations have also led to uncertainty with regard to the current classification of OI phenotypes. Bisphosphonates have been widely used to improve bone mass and decrease fractures in both children and adults with OI. While effective in many but not all children when administered for 2–4 years, bisphosphonates have not proven effective in adults with OI. Studies are limited for treatment of adults with teriparatide and denosumab. Advances have been reported in the surgical management of OI. Although the role of physical therapy in the management

  20. Dental management of severe dentinogenesis imperfecta in a mild form of osteogenesis imperfecta.

    Science.gov (United States)

    Stephen, L X G; Beighton, P

    2002-01-01

    Dentinogenesis Imperfecta (DI), in which the teeth are discolored, translucent and brittle, can occur in isolation as a familial trait and as a component of the skeletal dysplasia Osteogenesis Imperfecta (OI). In a Cape Town family, 20 persons in 3 generations had mild OI, with the additional manifestation of severe DI. The family was assessed at the Dental Genetic Unit of the University of the Western Cape and appropriate dental treatment was provided. In this setting, a detailed treatment plan was devised for a severely affected woman. This plan proved to be efficient and cost effective, and the final outcome was pleasing to the patient. Dentinogenesis Imperfecta is not uncommon and may well be encountered in conventional dental practice. The necessary clinical expertise is within the scope of the skills of the general dentist.

  1. [The child with osteogenesis imperfecta. Care plans].

    Science.gov (United States)

    Fernández Maldonado, Ana I; Gutiérrez Alonso, José Luis

    2002-06-01

    The authors state what is the nursing care to follow with a child affected by imperfect osteogenesis. This treatment is divided into three fundamental parts. In the first part, one plans out the psycho-sociological assistance the parents in question need in order to achieve their acceptance of a child suffering from a serious illness. In the second part, the authors describe the physical and psychological treatment which patients suffering imperfect osteogenesis should receive in order to avoid serious complications which can develop during their growth, treatment directed towards the family and the professional who shall care for this child. Finally in the third part, a child suffering imperfect osteogenesis shall receive the necessary knowledge and skills so that he/she can achieve maximum social integration. PMID:14508948

  2. Osteogenesis Imperfecta (Type IV with Dental Findings in Siblings

    Directory of Open Access Journals (Sweden)

    Shishir Ram Shetty

    2011-01-01

    Full Text Available Osteogenesis imperfecta (OI is a hereditary disorder characterized by increased tendency for bone fractures due to high fragility. The clinical and radiological features of OI manifest in different age groups, although the disease is congenital in nature. Besides bone fragility, features like laxity of the ligaments, blue sclera, growth retardation, and scoliosis are also observed. In severe cases, respiratory distress and death have been reported. The most important oral finding in OI is the presence of yellowish-brown-coloured brittle teeth characteristic of dentinogenesis imperfecta. Genetic factors play a very important role in the pathogenesis of OI either as a dominant or recessive factor. When a child has OI, there is a 25% chance of the sibling to have the same disorder. We report two cases of OI in siblings born to parents with a history of consanguineous marriage. The clinical and radiological features of the two cases are described in detail.

  3. Osteogenesis imperfecta: radiological view on the pediatric patient

    International Nuclear Information System (INIS)

    Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disorder of bone and connective tissue characterized by osteoporosis, fragile bones, hyper extensible joints, dentinogenesis imperfecta, bluish coloration of the sclerae, and adult-onset hearing loss. Detailed medical history, careful physical examination, radiographic features of fractures, and biochemical analysis of skin collagen are the four cornerstones of accurate diagnosis. A radiology specialist should be aware of subtle changes seen on radiographs as well as of specific osteogenesis features (i.e. popcorn calcifications) and difficult differential diagnosis (i.e. hypertrophic callus formation versus osteosarcoma; child abuse fractures versus true osteogenesis imperfecta). About 300 different mutations have been identified within COL1A1 and COL1A2 genes that encode the chains of type I collagen. Depending on the location of the mutation within the collagen gene, these produce a variety of clinical pictures which range from mild OI type I, lethal OI type II to severely deforming OI type III and mildly deforming OI type IV, OI type V is moderate in severity and it is similar to OI type IV, OI type VI is extremely rare and two recessive types of OI, types VII and VIII, were identified in 2006. Each of the eight types has a common radiologic appearance that helps in establishing the diagnosis. The purpose of this article is to give an as comprehensive as possible review of the radiological picture of OI in pediatric patients. Special emphasis will be given to specific radiological prognostic features as well as to the differential diagnosis. (author)

  4. Recent developments in osteogenesis imperfecta [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Joseph L. Shaker

    2015-09-01

    Full Text Available Osteogenesis imperfecta (OI is an uncommon genetic bone disease associated with brittle bones and fractures in children and adults. Although OI is most commonly associated with mutations of the genes for type I collagen, many other genes (some associated with type I collagen processing have now been identified. The genetics of OI and advances in our understanding of the biomechanical properties of OI bone are reviewed in this article. Treatment includes physiotherapy, fall prevention, and sometimes orthopedic procedures. In this brief review, we will also discuss current understanding of pharmacologic therapies for treatment of OI.

  5. Clinical perspectives on osteogenesis imperfecta versus non-accidental injury.

    Science.gov (United States)

    Pereira, Elaine Maria

    2015-12-01

    Although non-accidental injuries (NAI) are more common in cases of unexplained fractures than rare disorders such as osteogenesis imperfecta (OI), ruling out OI and other medical causes of fracture is always indicated. The majority of OI patients can be diagnosed with the help of family history, physical examination, and radiographic findings. In particular, there are a few radiological findings which are seen more commonly in NAI than in OI which may help guide clinician considerations regarding the probability of either of these diagnoses. At the same time, molecular testing still merits careful consideration in cases with unexplained fractures without obvious additional signs of abuse. PMID:26492946

  6. An unusual presentation of osteogenesis imperfecta type I

    Directory of Open Access Journals (Sweden)

    Rebelo M

    2011-04-01

    Full Text Available Marta Rebelo, Jandira Lima, José Diniz Vieira, José Nascimento CostaDepartment of Internal Medicine, University Hospital of Coimbra, Coimbra, PortugalAbstract: Osteogenesis imperfecta (OI is a rare inherited disorder with a broad spectrum of clinical and genetic variability. The genetic diversity involves, in the majority of the cases, mutations in one of the genes that encodes the type 1 collagen protein (COL1 A1 and COL1 A2, but it is not a requirement for the diagnosis. The most benign form is OI type I. The authors present a case report of a 25-year-old woman who had severe low back pain associated with incapacity to walk and breast-feed post-partum. Symptoms developed 2 weeks after delivery. The radiological examination revealed severe osteoporosis with no abnormalities in the laboratory findings. The clinical signs and a positive personal and family history of multiple fractures in childhood suggested OI type I, although other diagnosis, such as pregnancy-associated osteoporosis, was also considered. The atypical presentation of this rare disorder in adulthood calls attention to the need for early diagnosis for prompt treatment. Treatment of OI is never curative, but it improves the quality of the patient’s life.Keywords: osteogenesis imperfecta, collagen, pregnancy, osteoporosis

  7. Pediatric dental management of a patient with osteogenesis imperfecta and dentinogenesis imperfecta.

    Science.gov (United States)

    Muhney, Kelly; Campbell, Patricia Regener

    2007-01-01

    Osteogenesis imperfecta (OI) is a genetic disorder that affects all connective tissue. Clinical manifestations of OI include bone fragility, hyperlaxity of joints, hearing loss, abnormalities of stature and facial structure, blue sclerae, and dentinogenesis imperfecta (DI). OI is classified into four groups according to the severity and physical characteristics of the disease, although not all characteristics may be present in one individual. Currently, 20,000 to 50,000 individuals in the U.S. have been diagnosed with this disease. The aim of this article is to discuss medical and dental complications associated with OI and DI. A case presentation describes the clinical care of a patient from birth to age 12.

  8. Current and emerging treatments for the management of osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Elena Monti

    2010-08-01

    Full Text Available Elena Monti1, Monica Mottes1, Paolo Fraschini2, PierCarlo Brunelli3, Antonella Forlino4, Giacomo Venturi1, Francesco Doro1, Silvia Perlini1, Paolo Cavarzere1, Franco Antoniazzi11Department of Life Sciences and Reproduction, Pediatric Clinic University of Verona, Verona, Italy; 2Istituto Di Ricovero e Cura a Carattere Scientifico, ‘E. Medea’, Associazione La Nostra Famiglia, Bosisio Parini (LC, Italy; 3Divisione di Ortopedia Pediatrica, Spedali Civili, Brescia, Italy; 4Department of Biochemistry “A. Castellani”, University of Pavia, ItalyAbstract: Osteogenesis imperfecta (OI is the most common bone genetic disorder and it is characterized by bone brittleness and various degrees of growth disorder. Clinical severity varies widely; nowadays eight types are distinguished and two new forms have been recently described although not yet classified. The approach to such a variable and heterogeneous disease should be global and therefore multidisciplinary. For simplicity, the objectives of treatment can be reduced to three typical situations: the lethal perinatal form (type II, in which the problem is survival at birth; the severe and moderate forms (types III–IX, in which the objective is ‘autonomy’; and the mild form (type I, in which the aim is to reach ‘normal life’. Three types of treatment are available: non-surgical management (physical therapy, rehabilitation, bracing and splinting, surgical management (intramedullary rod positioning, spinal and basilar impression surgery and medical-pharmacological management (drugs to increase the strength of bone and decrease the number of fractures as bisphosphonates or growth hormone, depending on the type of OI. Suggestions and guidelines for a therapeutic approach are indicated and updated with the most recent findings in OI diagnosis and treatment.Keywords: osteogenesis imperfecta, bone genetic disorder, bone brittleness, “brittle bone disease”, connective tissue malfunction, short

  9. Prenatal transplantation of mesenchymal stem cells to treat osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Jerry KY Chan

    2014-10-01

    Full Text Available Osteogenesis Imperfecta (OI can be a severe disorder that can be diagnosed before birth. Transplantation of mesenchymal stem cells (MSC has the potential to improve the bone structure, growth and fracture healing. In this review we give an introduction to OI and MSC, and the basis for prenatal and postnatal transplantation in OI. We also summarize the two patients with OI who has received prenatal and postnatal transplantation of MSC.The findings suggest that prenatal transplantation of allogeneic MSC in OI is safe. The cell therapy is of likely clinical benefit with improved linear growth, mobility and reduced fracture incidence. Unfortunately, the effect is transient. For this reason postnatal booster infusions using same-donor MSC have been performed with clinical benefit, and without any adverse events.So far there is limited experience in this specific field and proper studies are required to accurately conclude on clinical benefits of MSC transplantation to treat OI.

  10. Collagen-derived markers of bone metabolism in osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Lund, A M; Hansen, M; Kollerup, Gina Birgitte;

    1998-01-01

    Markers of bone formation [C-terminal and N-terminal propeptides of procollagen I (PICP, PINP), osteocalcin and alkaline phosphatase] and bone resorption [C-terminal cross-linked telopeptide of collagen I (ICTP) and hydroxypyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr......)] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low, and the...... serum levels were lower in all children and adults with mild OI and a quantitative collagen defect than in patients with severe OI and a qualitative collagen I defect. ICTP, Pyr and Dpyr were generally normal or reduced, but elevated in severely affected adults with a qualitative collagen I defect. The...

  11. Clinical and Molecular Characterization of Osteogenesis Imperfecta Type V

    Science.gov (United States)

    Brizola, Evelise; Mattos, Eduardo P.; Ferrari, Jessica; Freire, Patricia O.A.; Germer, Raquel; Llerena Jr, Juan C.; Félix, Têmis M.

    2015-01-01

    Osteogenesis imperfecta type V (OI-V) has a wide clinical variability, with distinct clinical/radiological features, such as calcification of the interosseous membrane (CIM) between the radius-ulna and/or tibia-fibula, hyperplastic callus (HPC) formation, dislocation of the radial head (DRH), and absence of dentinogenesis imperfecta (DI). Recently, a single heterozygous mutation (c.-14C>T) in the 5′UTR of the IFITM5 gene was identified to be causative for OI-V. Here, we describe 7 individuals from 5 unrelated families that carry the c.-14C>T IFITM5 mutation. The clinical findings in these cases are: absence of DI in all patients, presence of blue sclera in 2 cases, and 4 patients with DRH. Radiographic findings revealed HPC in 3 cases. All patients presented CIM between the radius and ulna, while 4 patients presented additional CIM between the tibia and fibula. Spinal fractures by vertebral compression were observed in all individuals. The proportion of cases identified with this mutation represents 4% of OI cases at our institution. The clinical identification of OI-V is crucial, as this mutation has an autosomal dominant inheritance with variable expressivity. PMID:26648832

  12. Osteogenesis Imperfecta in Adult Twins Responded To Treatment With Pamidronate

    Directory of Open Access Journals (Sweden)

    Mehtap Çakır

    2011-06-01

    Full Text Available Bisphosphonates are strong inhibitors of bone resorption and are used in the treatment of osteoporosis. Bisphosphonates are known to be effective in prevention of fractures, improvement of bone mineral density as well as in relieving bone pain in osteogenesis imperfecta (OI patients. Recent studies have shown that especially intravenous pamidronate may be more effective when given in childhood and adolescence. This effect was also shown in adult OI patients in some clinical trials.22-year-old twin brothers known to have OI were admitted to our endocrinology and metabolism outpatient clinic. On medical history, OI was diagnosed at the age of three and for the last eight years, they were not able to walk and were using wheelchairs. On physical examination, blue sclerae and dentinogenesis imperfecta were detected in both patients. According to the expanded Sillence classification of OI, the clinical findings were consistent with type IV OI. Intravenous pamidronate treatment was given three times at four-month intervals, according to Montreal protocol. During this period, the patients were also doing isometric exercises and were on physical therapy, diet, and bioresonance therapy.At the end of one year, bone pain regressed significantly in both patients and they were able to walk independently. These outcomes demonstrate that in selected adult OI patients, intravenous pamidronate treatment may be beneficial in preventing bone fractures and relieving pain. Türk Jem 2011; 15: 39-43

  13. Advances in the Classification and Treatment of Osteogenesis Imperfecta.

    Science.gov (United States)

    Thomas, Inas H; DiMeglio, Linda A

    2016-02-01

    Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount, structure, or processing. The disease is characterized by an increased susceptibility to bony fracture. In addition to the skeletal phenotype, common additional extraskeletal manifestations include blue sclerae, dentinogenesis imperfecta, vascular fragility, and hearing loss. Medical management is focused on minimizing the morbidity of fractures, pain, and bone deformities by maximizing bone health. Along with optimizing Vitamin D status and calcium intake and physical/occupational therapy, individualized surgical treatment may be indicated. Pharmacological therapy with bisphosphonate medications is now routinely utilized for moderate to severe forms and appears to have a good safety profile and bone health benefits. New therapies with other anti-resorptives as well as anabolic agents and transforming growth factor (TGF)β antibodies are in development. Other potential treatment modalities could include gene therapy or mesenchymal cell transplant. In the future, treatment choices will be further individualized in order to reduce disease morbidity and mortality.

  14. Hearing Loss in Osteogenesis Imperfecta: Characteristics and Treatment Considerations

    Directory of Open Access Journals (Sweden)

    Joseph P. Pillion

    2011-01-01

    Full Text Available Osteogenesis imperfecta (OI is the most common heritable disorder of connective tissue. It is associated with fractures following relatively minor injury, blue sclerae, dentinogenesis imperfecta, increased joint mobility, short stature, and hearing loss. Structures in the otic capsule and inner ear share in the histologic features common to other skeletal tissues. OI is due to mutations involving several genes, the most commonly involved are the COL1A1 or COL1A2 genes which are responsible for the synthesis of the proalpha-1 and proalpha-2 polypeptide chains that form the type I collagen triple helix. A genotype/phenotype relationship to hearing loss has not been established in OI. Hearing loss is commonly found in OI with prevalence rates ranging from 50 to 92% in some studies. Hearing loss in OI may be conductive, mixed, or sensorineural and is more common by the second or third decade. Treatment options such as hearing aids, stapes surgery, and cochlear implants are discussed.

  15. Advances in the Classification and Treatment of Osteogenesis Imperfecta.

    Science.gov (United States)

    Thomas, Inas H; DiMeglio, Linda A

    2016-02-01

    Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount, structure, or processing. The disease is characterized by an increased susceptibility to bony fracture. In addition to the skeletal phenotype, common additional extraskeletal manifestations include blue sclerae, dentinogenesis imperfecta, vascular fragility, and hearing loss. Medical management is focused on minimizing the morbidity of fractures, pain, and bone deformities by maximizing bone health. Along with optimizing Vitamin D status and calcium intake and physical/occupational therapy, individualized surgical treatment may be indicated. Pharmacological therapy with bisphosphonate medications is now routinely utilized for moderate to severe forms and appears to have a good safety profile and bone health benefits. New therapies with other anti-resorptives as well as anabolic agents and transforming growth factor (TGF)β antibodies are in development. Other potential treatment modalities could include gene therapy or mesenchymal cell transplant. In the future, treatment choices will be further individualized in order to reduce disease morbidity and mortality. PMID:26861807

  16. Mutations in FKBP10 can cause a severe form of isolated Osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Steinlein Ortrud K

    2011-11-01

    Full Text Available Abstract Background Mutations in the FKBP10 gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found FKBP10 mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients in the first report indeed had isolated Osteogenesis imperfecta or if Bruck syndrome would have been the better diagnosis. Methods The patients described here are affected by severe autosomal recessive Osteogenesis imperfecta without contractures. Results Homozygosity mapping identified FKBP10 as a candidate gene, and sequencing revealed a base pair exchange that causes a C-terminal premature stop codon in this gene. Conclusions Our study demonstrates that FKBP10 mutations not only cause Bruck syndrome or Osteogenesis imperfecta type III but can result in a severe type of isolated Osteogenesis imperfecta type IV with prenatal onset. Furthermore, it adds dentinogenesis imperfecta to the spectrum of clinical symptoms associated with FKBP10 mutations.

  17. COL1A2 gene analysis in a Czech osteogenesis imperfecta patient: a candidate novel mutation in a patient affected by osteogenesis imperfecta type 3

    Directory of Open Access Journals (Sweden)

    Hrušková L

    2015-08-01

    Full Text Available Lucie Hrušková,1 Ivo Mařík,2,3 Stella Mazurová,1 Pavel Martásek,1 Ivan Mazura1 1Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 2Ambulant Centre for Defects of Locomotor Apparatus 1.1.c., Prague, Czech Republic; 3Faculty of Medical Studies, West Bohemia University, Pilsen, Czech RepublicAbstract: Osteogenesis imperfecta is a heritable bone fragility disease with a heterogenic genetic origin. Most cases result from mutations of either the COL1A1 gene or the COL1A2 gene. We identified a novel COL1A2 gene mutation in a Czech patient, born to unaffected parents, who was diagnosed according to clinical and anthropometric findings and radiographic features as having type 3 osteogenesis imperfecta, which is a severe form of this disease. The identified Gly814Trp mutation was predicted by a number of complementary bioinformatic programs to result in functional alteration of the protein. This case report provides both evidence of a novel COL1A2 mutation resulting in type 3 osteogenesis imperfecta and a genotype:phenotype correlation in this affected individual. Keywords: osteogenesis imperfecta type 3, collagen, alpha-2 (I chain, substitution, sequencing 

  18. Impact of three genetic musculoskeletal diseases: a comparative synthesis of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta

    OpenAIRE

    Dogba, Maman Joyce; Rauch, Frank; Douglas, Erin; Bedos, Christophe

    2014-01-01

    Achondroplasia, Duchenne muscular dystrophy, and osteogenesis imperfecta are among the most frequent rare genetic disorders affecting the musculoskeletal system in children. Rare genetic disorders are severely disabling and can have substantial impacts on families, children, and on healthcare systems. This literature review aims to classify, summarize and compare these non-medical impacts of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

  19. Osteogenesis Imperfecta em obstetrícia: Relato de caso Osteogénesis Imperfecta en obstetricia: Relato de caso Osteogenesis Imperfecta in pregnancy: Case report

    Directory of Open Access Journals (Sweden)

    Ticiana Goyanna Lyra

    2010-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Osteogenesis Imperfecta é uma condição rara, principalmente em pacientes obstétricas. A prevalência estimada é de 1/10.000 na população geral e 1/25.000 a 30.000 em pacientes obstétricas. O objetivo deste artigo foi relatar caso raro de gestante a termo, portadora de Osteogenesis Imperfecta, submetida à operação cesariana. RELATO DO CASO: Gestante de 23 anos, idade gestacional 38 semanas, admitida na maternidade com quadro de perda de líquido amniótico e contrações há 4 horas da admissão associado à ausência de movimentos fetais há 4 dias. Portadora de Osteogenesis Imperfecta forma leve, sem outras comorbidades associadas, não fazia uso de medicações nem acompanhamento pré-natal. Submetida à raquianestesia no interespaço L3-L4, mediana, punção única com agulha de Quincke 27G e injeção de bupivacaína 0,5% hiperbárica (10 mg e morfina (60 µg. Alta no segundo dia pós-operatório sem queixas. CONCLUSÕES: A fertilidade está preservada, principalmente naquelas pacientes com o tipo I da doença, e a gestação pode ser conduzida até o termo. O parto geralmente é cirúrgico devido a deformidades pélvicas da gestante, desproporção cefalopélvica e incidência aumentada de anormalidades na apresentação fetal. A importância do anestesiologista na equipe está no manejo perioperatório e na escolha da técnica anestésica mais apropriada a cada paciente.JUSTIFICATIVA Y OBJETIVOS: La Osteogénesis imperfecta es una condición rara, principalmente en pacientes obstétricas. La prevalencia estimada es de 1/10.000 en la población general y 1/25.000 a 30.000 en pacientes obstétricas. El objetivo de este artículo, fue relatar un caso raro de gestante a término portadora de osteogénesis imperfecta sometida a operación por cesárea. RELATO DEL CASO: Gestante de 23 años, edad gestacional 38 semanas, admitida en maternidad con un cuadro de pérdida de líquido amniótico y contracciones

  20. Clinical manifestations and dental management of dentinogenesis imperfecta associated with osteogenesis imperfecta: Case report.

    Science.gov (United States)

    Abukabbos, Halima; Al-Sineedi, Faisal

    2013-10-01

    Dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta (OI) is a genetic disorder that affects the connective tissues and results in dentine dysplasia. This case report discusses the systemic and dental manifestations of OI and DI in a 4-year-old child, with moderate presentation of both disorders, who was treated at King Fahd Military Medical Complex in Dhahran. Dental treatment included the use of strip and stainless-steel crowns under local anesthesia, as well as behavior modification techniques. Rigorous home care instructions, including reinforcement of the oral hygiene practice and avoidance of any episode that may lead to bone fracture, were discussed with the parents. The case was reevaluated at 3-month follow-up visits, wherein the medical and dental histories were updated, the child's growth was monitored, periodic clinical and radiographic examinations were performed, and the oral hygiene was evaluated via the debris index score and caries risk assessment. Further treatment of the permanent dentition may be needed in the future.

  1. Mortality and Causes of Death in Patients With Osteogenesis Imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Canudas-Romo, Vladimir;

    2016-01-01

    Osteogenesis imperfecta (OI) is a hereditary connective tissue disease that causes frequent fractures. Little is known about causes of death and length of survival in OI. The objective of this work was to calculate the risk and cause of death, and the median survival time in patients with OI...... five to one to the OI cohort. We calculated hazard ratios for all-cause mortality and subhazard ratios for cause-specific mortality in a comparison of the OI cohort and the reference population. We also calculated all-cause mortality hazard ratios for males, females, and age groups (0 to 17.99 years......, 18.00 to 34.99 years, 35.00 to 54.99 years, 55.00 to 74.99 years, and >75 years). We identified 687 cases of OI (379 women) and included 3435 reference persons (1895 women). A total of 112 patients with OI and 257 persons in the reference population died during the observation period. The all-cause...

  2. AB129. Osteogenesis imperfecta: clinical features and bisphosphonate treatment outcome

    Science.gov (United States)

    Can, Ngoc Thi Bich; Vu, Dung Chi; Bui, Thao Phuong; Nguyen, Khanh Ngoc

    2015-01-01

    Background and objective Osteogenesis imperfecta (OI) comprises a group of disorders principally affecting type I collagen which result in increased bone fragility. Children with severe OI suffer recurrent fractures, resulting in severe deformity and growth stunting in many cases, with loss of independent ambulation by the teenage years in over 50% of cases. Recently, cyclical intravenous treatment with pamidronate has proven of benefit to children with severe forms of OI. This article aims to describle clinical features and laboratory manifestations of patient with OI and evaluate outcome of bisphosphonate management. Methods Clinical features, biochemical finding, and management outcome of 104 cases were study. The patients were classified into four major subtypes of Sillience et al. 1979. Patients with severe types were treatment with pamidronate (Aredia) used Rauch protocol 2003. Results Now we have 196 patients (87 females and 109 males) but we studied focus on 104 patients from 98 families (60 males, 44 females) onset at 2.1±3.0 years (median 0.35) with the average fracture bone of 5.9±4.4 times. In there, 17% type I, 8% type II, 63% type III, and 12% type IV. Clinical features include of intrauterine fracture visible on ultrasound 35%, bone deformation after birth 68%, triangle face 76%, long bone deformation 91%, chest deformation 46%, scoliosis 27%, short status 90%, blue sclera 83%, dentinogenesis imperfecta 20%, hearing loss 6%. Thirty patients have been treated with pamidronate at 3.2±3.7 years (4 months to 8 years) during 13±0.8 months (6-30 months). Fourteen patients had fracture bone after 6 months of treatment but no patients had fracture bone after 12 months. Seven patients had been treatment after 1.6±0.5 years, BMD increase from 0.39±0.311 to 0.79±0.105 g/cm2 (P<0.05). One patient had fever reaction after first pamidronate infusion but controlled with standard antipyretic therapy, and do not recur in later treatments. Conclusions OI has

  3. [Oral cavity features in patients suffering from osteogenesis imperfecta].

    Science.gov (United States)

    Alania, K N; Iverieli, M B; Abashidze, N O; Gogishvili, Kh B; Chigladze, T T

    2011-04-01

    Osteogenesis Imperfecta (OI) is a rare hereditary connective tissue disorder. This pathology is characterized by disruption of biosynthesis of Type I collagen, and production of limited amount of defective and imperfect collagens. This causes decrease in bone mass of human body, bones become fragile and brittle, resulting in unreasonable multiple fractures. Reportedly, number of patients with OI ranges between 32-38 in Georgia. However, exact number of patients, including children and their parents, is unknown. Dentinogenesis Imperfecta (DI; DGI) and skeletal malocclusion occupy special place in varied spectrum of OI clinical symptoms. We studied 14 patients: 9 women (64.3%), 5 men (35.7%) and divided them in three age groups: I - 2.5-6 years - period of primary dentition (28.6%), II - 6-14 years - period of changing teeth dentition (35.7%) and III - above 14 years - period of permanent dentition (35.7%). 28.5% of screened patients had one of the symptoms of DI, such as tooth discoloration. Discoloration of primary teeth was revealed in 4 patients (primary dentition). Another symptom of DI, such as early abrasion, was detected in 5 patients i.e. 35.71%. This was divided in the following manner: I age group - 3 cases, II and III age groups - 1-1 cases. It was also observed that early abrasion of primary teeth prevails over permanent. One of DI's radiographic symptoms, such as peculiar form of teeth crown and root, was revealed in 21.4% or in 3 patients, 2 of whom had bulbous crown, and the third one deformed (curved) root. Peculiar characteristics of DI, such as increased constriction of the coronal-radicular junction, obliterated pulp chamber, short and narrow roots, were not observed in the patients examined. Interesting characteristic of DI, such as periapical destruction of intact tooth root, was revealed in the form of bone defect in 7.1% of those examined (1 patient). Therefore, out of examined 14 patients with OI - DI had 6 patients or 42.85% of cases. Also

  4. Childhood Osteoporosis and Presentation of Two Cases with Osteogenesis Imperfecta Type V / Osteoporoza V Otroški Dobi in Predstavitev Dveh Bolnikov Z Osteogenesis Imperfecta Tipa V

    Directory of Open Access Journals (Sweden)

    Bratanic Nina

    2015-03-01

    Full Text Available Uvod. Osteogenesis imperfecta (OI je vzročno heterogena bolezen, katere značilnost je osteoporoza v otroštvu. Pri vseh opisanih bolnikih s podtipom OI tipa V je vzrok bolezni ista mutacija c.-14C>T gena IFITM5. Kljub temu med bolniki obstaja izrazita fenotipska variabilnost v klinični sliki, toda opisan je le dober odgovor na zdravljenje z bisfosfonati.

  5. Osteogenesis imperfecta in childhood: MR imaging of basilar impression

    International Nuclear Information System (INIS)

    Objective: To determine on radiographs the presence of Basilar Impression (BI) in children with Osteogenesis Imperfecta (OI). To confirm this sign and altered geometrical relationships of the craniocervical junction in course of time with magnetic resonance imaging (MRI). Methods and patients: In a cohort study of 130 patients with OI (OI type I: 85; OI type III: 21; OI type IV: 24) lateral radiographs of the skull and cervical spine were made in a standardised way. MRI scans were performed when BI was suspected based upon protrusion of the odontoid above Chamberlain's line. Intracranial abnormalities as well as the basal angle were described. Neurological examination was performed in patients with conclusive BI at MRI-scan. Results and discussion: In eight patients BI could be confirmed by MRI-scan. None of the children had or developed in time neurological symptoms or signs. Follow up of BI by MRI scans was done in seven patients (mean: 5 years; range: 2-6 years). No alteration of intracranial findings were seen at subsequent investigation, although in one child Chamberlain's line increased from 8 (first MRI) to 15 mm (last MRI). BI can be diagnosed by radiographs but in the extreme osteoporotic bone and altered anatomy of the craniocervical junction of children with OI MRI is preferable. As intracranial pathology can be demonstrated by MRI, also a relation can be laid to possible neurological symptoms and signs at clinical examination. Conclusion: In our cohort study no alteration of the intracranial contents was seen at subsequent MRI scans. Although anatomic deformations exist in BI, no neurological symptoms or signs were present in our study and no operative reconstruction had to be performed. Periodical MRI-scan has not been of influence on the clinical decision making process. At the moment we perform a MRI-scan if BI is suspected at lateral skull radiographs. The MRI images serve as reference findings to anticipate on possible future symptoms and signs of

  6. Traumatic and spontaneous scleral rupture and uveal prolapse in osteogenesis imperfecta.

    Science.gov (United States)

    Pirouzian, Amir; O'Halloran, Henry; Scher, Colin; Jockin, Yvett; Yaghmai, Reza

    2007-01-01

    Three cases of severe globe injuries due to scleral fragility in osteogenesis imperfecta patients between the ages of 4 and 15 years are reported. Patient 1 had complete loss of vision. Patients 2 and 3 suffered non-sight-threatening scleral perforation. All 3 patients had no previous knowledge of recommendation for eyewear protection. PMID:17913179

  7. Osteogenesis imperfecta : profiles of motor development as assessed by a postal questionnaire

    NARCIS (Netherlands)

    Engelbert, RHH; Uiterwaal, CSPM; Gulmans, VAM; Pruijs, HEH; Helders, PJM

    2000-01-01

    This study was performed to achieve more detailed information regarding the age and sequence in the development of motor milestones in the different types of osteogenesis imperfecta (OI). The parents of 98 patients with a diagnosis of OI were sent a questionnaire regarding the age at which patients

  8. Phlorotannin-incorporated Mesenchymal Stem Cells and their Promising Role in Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Tehseen Fatima Ali

    2012-07-01

    Full Text Available Osteogenesis imperfecta as the name suggests, is a bone disorder characterised by imperfect bone mineralisation and development. The key defect lies in the osteoblast–osteoid cycle, leading to insufficient calcification and consequently weak bones. Osteogenesis imperfecta patients are prone to fractures. Till date, numerous growth hormone/synthetic analogues have been used therapeutically in osteogenesis imperfecta patients and they do provide temporary relief, but not without numerous unwanted side effects. The intervention offered by such treatments is mainly at the symptomatic level, with temporary pain relief and some degree of mineralisation of available osteoids; but the root cause of the disease remains unattended. Such treatment modalities fail to promote mesenchymal stem cell osteogenic differentiation and tackle the fundamental deficiency of osteoids. This paper suggests a unique and hitherto unimplemented approach for treatment of osteogenesis imperfecta at the cellular level through application of a natural source, ‘Brown algae isolated phlorotannins’, which promote mesenchymal stem cell differentiation by increasing alkaline phosphatase activity, calcific mineralisation and total protein and collagen synthesis. This natural extract, when integrated directly with mesenchymal stem cells, will boost cellular differentiation into healthy bone-forming cells. The modality will strengthen the bone intrinsically and without the adverse reactions of routine pharmacotherapeutic agents.

  9. Osteogénesis imperfecta con manifestaciones en el periodo neonatal Neonatal Presentation of Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Gilberto Rodríguez-Herrera

    2009-04-01

    and given genetic counseling to parents. The osteogenesis imperfecta has a genetic background that affects connective tissue integrity, associated with collagen synthesis mutations, being dominant or recessive autosomic inheritance. In the majority of cases, diagnosis of IO is easy on the basis of clinical and radiological findings; for this reason must be important to emphasize on bone structure studies, because patients may develop cystic, dense or fragile changes. This case presents a patient who has osteogenesis imperfecta type II; we pretend to discuss the differences between Ol’s types.

  10. Osteogénesis imperfecta en una gatita de 2 meses - Osteogenesis imperfect in a kitten 2 months

    OpenAIRE

    Rodríguez, O.; Turco, V; Vilar, JM; Morales M; Miró, F.; Martinez, A. (Alfredo)

    2012-01-01

    ResumenLa ostegénesis imperfecta es una enfermedad congénita. Normalmente es causada por un gen que produce el colágeno tipo I, fundamental para el desarrollo del hueso.SummaryOsteogenesis imperfecta is a congenital disorder. It is normally caused by the gene that produces type I collagen, which is responsible for bone formation.

  11. DENTINOGENESIS IMPERFEC TA WITH OSTEOGENESIS IMPERFECTA: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Jesudass

    2015-03-01

    Full Text Available Dentinogegesis imperfecta (DI represents a group of hereditary conditions that are characterized by abnormal dentin formation. These conditions are genetically and clinically heterogenous and can affect only the teeth or can be associated with the condition Osteogegesis imperfecta . The Osteogegesis imperfecta (OI or the disease of fragile bones is a hereditary pathology affecting different tissues especially the bone. The teeth of DI cases wear more easily and excessively and also more susceptible to dental caries compa red to normal teeth. Early prosthodontic rehabilitation can prevent or delay the wear as well as loss of teeth in DI. Herewith, we present case report of 10yr old boy with discolored, severely attrited permanent teeth with sinus openings. A long with system ic abnormalities like blue sclera, bow legs, protruded sternum. The case was diagnosed as Dentinogegesis imperfecta type I and discussed in this case report.

  12. Perinatal lethal osteogenesis imperfecta in a Thai newborn: the autopsy and histopathogical findings.

    Science.gov (United States)

    Himakhun, Wanwisa; Rojnueangnit, Kitiwan; Prachukthum, Sariya

    2012-01-01

    Osteogenesis imperfecta (OI) is an inherited disorder of type I collagen synthesis with an estimate incidence of I in 100,000 live births. Among all types, OI type II is the most severe type with perinatal death. The authors describes a male neonate with characteristic features of osteogenesis imperfect type II, including short crumpling limbs, beaded ribs, poorly bony ossification and blue sclera. Autopsy with histological study revealed not only multiple fractures, but pulmonary hypoplasia and intracerebral hemorrhages were also present. Both are the leading causes of death in the lethal type OI patients. PMID:23964465

  13. A rare presentation of a child with osteogenesis imperfecta and congenital laryngomalacia for herniotomy

    Directory of Open Access Journals (Sweden)

    Roshith Chandran

    2011-01-01

    Full Text Available Sometimes anaesthesiologists come across rare congenital anomalies in their practice. The inherent complications associated with the disorder necessitate tailor-made approaches for providing anaesthesia to even seemingly simple surgical interventions. Here, we share our experience of anaesthesia management of an infant with congenital laryngomalacia and recently diagnosed osteogenesis imperfecta type 1 who had presented to us with an acute abdomen for a semi-emergency herniotomy.

  14. A rare presentation of a child with osteogenesis imperfecta and congenital laryngomalacia for herniotomy.

    Science.gov (United States)

    Chandran, Roshith; Dave, Nandini; Padvi, Amit; Garasia, Madhu

    2011-09-01

    Sometimes anaesthesiologists come across rare congenital anomalies in their practice. The inherent complications associated with the disorder necessitate tailor-made approaches for providing anaesthesia to even seemingly simple surgical interventions. Here, we share our experience of anaesthesia management of an infant with congenital laryngomalacia and recently diagnosed osteogenesis imperfecta type 1 who had presented to us with an acute abdomen for a semi-emergency herniotomy. PMID:22174477

  15. Orthopaedic complications of osteogenesis imperfecta; Les complications orthopediques de l'osteogenese imparfaite

    Energy Technology Data Exchange (ETDEWEB)

    Azrak, S.; Ksyar, R.; Ben Rais, N. [hOpital Ibn Sina, CHU de Rabat-Sale, Service de Medecine Nucleaire, Rabat-Sale (Morocco)

    2009-12-15

    Osteogenesis imperfecta is a genetic disease characterized by bone frailty. It is generally caused by an abnormal production of collagen, which is the main fibrous protein of the bone. Collagen is also present in the skin, tendons, the sclera of the eye and dentin. The most frequent manifestation of osteogenesis imperfecta is the occurrence of multiple fractures without major trauma. Severity and timing of the attack varies widely: some patients sustain a significant number of fractures during early childhood which may have a serious impact on growth, while others will have some fractures separated by a few years. In all cases, the bone strength improves in adulthood. The bone fractures cause pain and bone deformities sometimes result in a smaller size. Scoliosis is frequent and associated with painful vertebral collapses. We present a case of osteogenesis imperfecta in a 40-year-old adult and we describe the various orthopaedic complications of the disease, stressing the role of bone scintigraphy in the diagnosis and monitoring of these complications. (authors)

  16. Immunocytochemical detection of dentin matrix proteins in primary teeth from patients with dentinogenesis imperfecta associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    G. Orsini

    2014-10-01

    Full Text Available Dentinogenesis imperfecta determines structural alterations of the collagen structure still not completely elucidated. Immunohistochemical analysis was used to assay Type I and VI collagen, various non-collagenous proteins distribution in human primary teeth from healthy patients or from patients affected by type I dentinogenesis imperfecta (DGI-I associated with osteogenesis imperfecta (OI. In sound primary teeth, an organized well-known ordered pattern of the type I collagen fibrils was found, whereas atypical and disorganized fibrillar structures were observed in dentin of DGI-I affected patients. Expression of type I collagen was observed in both normal and affected primary teeth, although normal dentin stained more uniformly than DGI-I affected dentin. Reactivity of type VI collagen was significantly lower in normal teeth than in dentin from DGI-I affected patients (P<0.05. Expressions of dentin matrix protein (DMP-1 and osteopontin (OPN were observed in both normal dentin and dentin from DGI-I affected patients, without significant differences, being DMP1 generally more abundantly expressed. Immunolabeling for chondroitin sulfate (CS and biglycan (BGN was weaker in dentin from DGI-I-affected patients compared to normal dentin, this decrease being significant only for CS. This study shows ultrastructural alterations in dentin obtained from patients affected by DGI-I, supported by immunocytochemical assays of different collagenous and non-collagenous proteins.

  17. Immunocytochemical detection of dentin matrix proteins in primary teeth from patients with dentinogenesis imperfecta associated with osteogenesis imperfecta.

    Science.gov (United States)

    Orsini, G; Majorana, A; Mazzoni, A; Putignano, A; Falconi, M; Polimeni, A; Breschi, L

    2014-12-01

    Dentinogenesis imperfecta determines structural alterations of the collagen structure still not completely elucidated. Immunohistochemical analysis was used to assay Type I and VI collagen, various non-collagenous proteins distribution in human primary teeth from healthy patients or from patients affected by type I dentinogenesis imperfecta (DGI-I) associated with osteogenesis imperfecta (OI). In sound primary teeth, an organized well-known ordered pattern of the type I collagen fibrils was found, whereas atypical and disorganized fibrillar structures were observed in dentin of DGI-I affected patients. Expression of type I collagen was observed in both normal and affected primary teeth, although normal dentin stained more uniformly than DGI-I affected dentin. Reactivity of type VI collagen was significantly lower in normal teeth than in dentin from DGI-I affected patients (P<0.05). Expressions of dentin matrix protein (DMP)-1 and osteopontin (OPN) were observed in both normal dentin and dentin from DGI-I affected patients, without significant differences, being DMP1 generally more abundantly expressed. Immunolabeling for chondroitin sulfate (CS) and biglycan (BGN) was weaker in dentin from DGI-I-affected patients compared to normal dentin, this decrease being significant only for CS. This study shows ultrastructural alterations in dentin obtained from patients affected by DGI-I, supported by immunocytochemical assays of different collagenous and non-collagenous proteins.

  18. [The oral aspects of osteogenesis imperfecta. A clinical case report].

    Science.gov (United States)

    Moniaci, D; Migliario, M; Flecchia, G; Re, G

    1989-10-01

    The oral symptoms observable in patients with imperfect osteogenesis are described and a clinical case that makes a contribution to our knowledge of a rarely encountered pathology is reported. PMID:2615733

  19. Osteogénesis imperfecta en una gatita de 2 meses - Osteogenesis imperfect in a kitten 2 months

    Directory of Open Access Journals (Sweden)

    Rodríguez, O

    2012-01-01

    Full Text Available ResumenLa ostegénesis imperfecta es una enfermedad congénita. Normalmente es causada por un gen que produce el colágeno tipo I, fundamental para el desarrollo del hueso.SummaryOsteogenesis imperfecta is a congenital disorder. It is normally caused by the gene that produces type I collagen, which is responsible for bone formation.

  20. [Massive fecal impaction in a patient with osteogenesis imperfecta].

    Science.gov (United States)

    Bujanda, L; Beguiristain, A; Villar, J M; Medrano, M A; Arana, J; Alvarez-Caperochipi, J; Arenas, J I

    1994-05-01

    The case of a 22 year old male with massive faecal impaction and anorectal mechanical stenosis caused by multiples bone fractures and pelvic deformities secondary to imperfect osteogenesis is reported. The patient was treated with subtotal colectomy and permanent colostomy. PMID:8049109

  1. Swellings over the Limbs as the Earliest Feature in a Patient with Osteogenesis Imperfecta Type V

    Directory of Open Access Journals (Sweden)

    Ali Al Kaissi

    2014-01-01

    Full Text Available Swellings over the upper and lower limbs were encountered in a one-year-old child. Skeletal survey showed a constellation of distinctive radiographic abnormalities of osteoporosis, hyperplastic callus and ossification of the interosseous membrane of the forearm, femora, and to lesser extent the tibiae. Neither wormian bones of the skull nor dentinogenesis imperfecta was present. Genetic tests revealed absence of mutation in COL1A1 or COL1A2 genes, respectively. The overall phenotypic features were consistent with the diagnosis of osteogenesis imperfecta type V (OI-V. The aim of this paper is to distinguish between swellings because of intrinsic bone disorders and these due to child physical abuse.

  2. SUCCESSFUL USE OF THE PONSETI METHOD IN THE TREATMENT OF FOUR CHILDREN WITH CLUBFOOT ASSOCIATED WITH OSTEOGENESIS IMPERFECTA TYPE I

    OpenAIRE

    Valery Fyodorovich Blandinskiy; Maksim Aleksandrovich Vavilov; Maksim Aleksandrovich Baushev

    2014-01-01

    Conservative treatment of congenital clubfoot deformity in osteogenesis imperfecta is very challenging because the high risk of pathological fracture. There is little to no data of such cases hadn’t been found to be described in the literature. We present a child with osteogenesis imperfect and clubfoot deformity, who had been previously inefficiently treated with plaster casts and developed pathological fractures of the tibia. The use of Ponseti method allowed us to completely correct the de...

  3. SUCCESSFUL USE OF THE PONSETI METHOD IN THE TREATMENT OF FOUR CHILDREN WITH CLUBFOOT ASSOCIATED WITH OSTEOGENESIS IMPERFECTA TYPE I

    Directory of Open Access Journals (Sweden)

    Валерий Федорович Бландинский

    2014-06-01

    Full Text Available Conservative treatment of congenital clubfoot deformity in osteogenesis imperfecta is very challenging because the high risk of pathological fracture. There is little to no data of such cases hadn’t been found to be described in the literature. We present a child with osteogenesis imperfect and clubfoot deformity, who had been previously inefficiently treated with plaster casts and developed pathological fractures of the tibia. The use of Ponseti method allowed us to completely correct the deformity and avoid complications.

  4. [Bilateral quadriceps rupture in a patient with osteogenesis imperfecta. A case report].

    Science.gov (United States)

    Salcedo-Dueñas, Jesús Alejandro; Torres Castro, Carlos; Estrada Gómez, José Andrés; Algarín Reyes, José Antonio; Bello González, Alejandro

    2009-01-01

    We present the case of a 24-year-old patient with bilateral quadriceps rupture and history of type I congenital osteogenesis imperfecta diagnosed clinically and with ultrasound. Bilateral quadriceps tenoplasty was performed with an anterior approach and without any complications. The patient was discharged with bilateral neoprene knee-guards. The sutures were removed at the 21-day follow-up visit, rehabilitation was started at six weeks and the patient was doing well at the 2- and 3-month follow-up visits. Timely management and early rehabilitation contribute to decrease the risk of sequelae despite the poor functional prognosis.

  5. Sequence Environment of Mutation Affects Stability and Folding in Collagen Model Peptides of Osteogenesis Imperfecta

    OpenAIRE

    Bryan, Michael A.; Cheng, Haiming; Brodsky, Barbara

    2011-01-01

    Osteogenesis Imperfecta (OI), a disorder characterized by fragile bones, is often a consequence of missense mutations in type I collagen which change one Gly in the repeating (Gly-Xaaa-Yaa)n sequence to a larger amino acid. The impact of local environment and the identity of the residue replacing Gly was investigated using two sets of triple-helical peptides. Gly mutations in the highly stable (Pro-Hyp-Gly)10 system are compared with mutations in T1-865 peptides where the mutation is located ...

  6. [The combined treatment of osteogenesis imperfecta in children].

    Science.gov (United States)

    Berezhnoĭ, A P; Shilov, A V; Belova, N A; Snetkov, A I

    1989-12-01

    The authors present the results of complex drug and orthopaedic treatment of children with imperfect osteogenesis. 40 patients were treated with a somatotropic hormone, calcitrin and vitamin D metabolites (oxydevit and dihydrocholecalciferol). In 20 of these patients corrective osteotomies of the long bones of the lower extremities combined with metal osteosynthesis with rods and massive plates were performed. In a number of patients osteoplasty with long cortical allografts was made. After the treatment all the children were able to move independently either with the aid of unloading orthopaedic apparatuses (17 patients), or without them (3 patients). PMID:2628828

  7. Non-traumatic hypertrophic callus of the fibula mimicking osteosarcoma in osteogenesis imperfecta type V: a case report.

    Science.gov (United States)

    Radu, Arnold; Kanza, Rene Epunza; Barabas, Dezso; Lessard, Michel; Berube, Michel

    2014-09-01

    We report a case of hyperplastic callus mimicking osteosarcoma in the fibula of a patient with osteogenesis imperfecta type V. Among the various imaging modalities, computed tomography was the most useful in distinguishing this rare process from a malignant entity. In addition, simple radiographs demonstrated the presence of characteristic "zebra lines", a manifestation of cyclic bisphosphonate therapy during childhood. PMID:24733362

  8. Association between joint hypermobility, scoliosis, and cranial base anomalies in paediatric Osteogenesis imperfecta patients: a retrospective cross-sectional study

    OpenAIRE

    Arponen, Heidi; MÀkitie, Outi; Waltimo-Sirén, Janna

    2014-01-01

    Abstract Background Joint hypermobility is a common clinical characteristic of patients with Osteogenesis imperfecta (OI), a disorder with serious comorbidities of scoliosis and cranial base anomalies. This study aimed at evaluating how prevalent joint hypermobility is in paediatric OI patients, and to find out whether it serves as a potential predictive marker of the different spinal complications; scoliosis and craniovertebral anomalie...

  9. Spontaneous and simultaneous bilateral rupture of the quadriceps tendon in a patient with osteogenesis imperfecta: a case report.

    Science.gov (United States)

    Figueroa, David; Calvo, Rafael; Vaisman, Alex

    2006-03-01

    Bilateral rupture of the quadriceps tendon is an uncommon and serious injury that usually occurs in middle aged to elderly patients. It is frequently associated with chronic metabolic disorders like diabetes, hyperparathyroidism, gout, chronic renal failure or the chronic use of steroids. We report a case of spontaneous bilateral rupture of the quadriceps tendon in a patient with osteogenesis imperfecta.

  10. Next-generation sequencing of common osteogenesis imperfecta-related genes in clinical practice.

    Science.gov (United States)

    Árvai, Kristóf; Horváth, Péter; Balla, Bernadett; Tobiás, Bálint; Kató, Karina; Kirschner, Gyöngyi; Klujber, Valéria; Lakatos, Péter; Kósa, János P

    2016-01-01

    Next generation sequencing (NGS) is a rapidly developing area in genetics. Utilizing this technology in the management of disorders with complex genetic background and not recurrent mutation hot spots can be extremely useful. In this study, we applied NGS, namely semiconductor sequencing to determine the most significant osteogenesis imperfecta-related genetic variants in the clinical practice. We selected genes coding collagen type I alpha-1 and-2 (COL1A1, COL1A2) which are responsible for more than 90% of all cases. CRTAP and LEPRE1/P3H1 genes involved in the background of the recessive forms with relatively high frequency (type VII and VIII) represent less than 10% of the disease. In our six patients (1-41 years), we identified 23 different variants. We found a total of 14 single nucleotide variants (SNV) in COL1A1 and COL1A2, 5 in CRTAP and 4 in LEPRE1. Two novel and two already well-established pathogenic SNVs have been identified. Among the newly recognized mutations, one results in an amino acid change and one of them is a stop codon. We have shown that a new full-scale cost-effective NGS method can be developed and utilized to supplement diagnostic process of osteogenesis imperfecta with molecular genetic data in clinical practice. PMID:27335225

  11. Next-generation sequencing of common osteogenesis imperfecta-related genes in clinical practice

    Science.gov (United States)

    Árvai, Kristóf; Horváth, Péter; Balla, Bernadett; Tobiás, Bálint; Kató, Karina; Kirschner, Gyöngyi; Klujber, Valéria; Lakatos, Péter; Kósa, János P.

    2016-01-01

    Next generation sequencing (NGS) is a rapidly developing area in genetics. Utilizing this technology in the management of disorders with complex genetic background and not recurrent mutation hot spots can be extremely useful. In this study, we applied NGS, namely semiconductor sequencing to determine the most significant osteogenesis imperfecta-related genetic variants in the clinical practice. We selected genes coding collagen type I alpha-1 and-2 (COL1A1, COL1A2) which are responsible for more than 90% of all cases. CRTAP and LEPRE1/P3H1 genes involved in the background of the recessive forms with relatively high frequency (type VII and VIII) represent less than 10% of the disease. In our six patients (1–41 years), we identified 23 different variants. We found a total of 14 single nucleotide variants (SNV) in COL1A1 and COL1A2, 5 in CRTAP and 4 in LEPRE1. Two novel and two already well-established pathogenic SNVs have been identified. Among the newly recognized mutations, one results in an amino acid change and one of them is a stop codon. We have shown that a new full-scale cost-effective NGS method can be developed and utilized to supplement diagnostic process of osteogenesis imperfecta with molecular genetic data in clinical practice. PMID:27335225

  12. Tomographic imaging of collagen-mineral interaction: implications for osteogenesis imperfecta.

    Science.gov (United States)

    Landis, W J

    1995-01-01

    The novel method of high voltage electron microscopic tomography (3D) has been applied for the first time to examine ultrastructural features and spatial relations between collagen fibrils and mineral crystals in a mouse mutant (oim/oim) which replicates a moderate to severe form of osteogenesis imperfecta. The animal produces collagen consisting of the alpha1(I) homotrimer and has a brittle calcified skeleton. Three-dimensional image reconstructions of the Achilles tendons, which were found to mineralize in the mutant mice, revealed that their composite crystals were different in their structural appearance and spatial association with collagen compared to that determined in normal calcified tissues. These results indicate that the nature of the organic matrix of a mineralizing tissue critically influences the formation, structure, and location of the constituent mineral and, further, the data are interpreted as suggesting that the unusual structural and organizational interaction between mineral and collagen underlies the inherent brittleness and weakness of calcification in this model of osteogenesis imperfecta.

  13. [Children with osteogenesis imperfecta. An infrequent but important disease].

    Science.gov (United States)

    Fernández Maldonado, A I; Gutiérrez Alonso, J L

    2001-05-01

    Imperfect osteogenesis is a disease which is included in the group of the osseous dysplasias having a heterogeneous genetic character and whose basic defect is an alteration in the synthesis of Procollagen I. This leads to a serious fragility in skeletal structures as well as in exoskeletal structures, causing multiple fractures and deformities. The absence of a truly effective medical, surgical or orthopedic treatment makes correctly planned nursing care acquire vital importance in order to succeed in avoiding, and diminishing, fractures and deformities due to an inadequate handling of these patients; while to the contrary contributing to success in integrating these patients into society in the best possible conditions. This is the first of two articles which the authors will dedicate to this disease; this disease will be described in this first article, while the second one will concentrate exclusively on nursing treatments recommended for patients suffering from this disease. PMID:12033039

  14. Osteogenesis Imperfecta Type II with Congenital Heart Disease

    Directory of Open Access Journals (Sweden)

    Sona Khangare

    2008-05-01

    Full Text Available Objective: Osteogenesis imperfect (OI is an inherited disorder of type1 collagen synthesis with varied complication. OI type II is a perinatally lethal variety, characterized by short limbs, broad long bones, radiologic evidence of severe osseous fragility and defective ossification. These patient usually are stillborn or die in early infancy of respiratory failure. It has a wide range of phenotypic expressions, but cardiovascular anomalies tend to be rare association. When they do occur, they usually consist of aortic or mitral valve disease. Case Presentation: Here we come across a rare case of OI type II in a neonate with acyanotic congenital heart disease. Echocardiography revealed moderate size ostium secundum atrial septal defect without pulmonary hypertension. The patient expired after 6 hour of life. Conclusion: Any case of OI should be screened for congenital cardiovascular defect and another abnormality.

  15. Atypical femoral fracture in an osteogenesis imperfecta patient successfully treated with teriparatide

    DEFF Research Database (Denmark)

    Holm, Jakob; Eiken, Pia; Hyldstrup, Lars;

    2014-01-01

    : This is a case report of an AFF treated with teriparatide. RESULTS: The patient was treated with hormone replacement therapy for 18 years and bisphosphonates for 9 years before suffering a spontaneous AFF in the form of a dislocated noncomminute transverse fracture of the right femoral shaft, and an open......OBJECTIVE: We report a case of a successfully healed atypical femoral fracture (AFF) following treatment with teriparatide in a patient with osteogenesis imperfecta (OI). To our knowledge, no successful treatment of AFFs with teriparatide in this subpopulation has ever been described. METHODS...... reduction and internal fixation (ORIF) with a T2 Femoral Nail was done. Due to nonunion and another fracture distal to the nail, the patient was reoperated on with exchange ORIF and off-label treatment with teriparatide 20 μg/day was started. An X-ray 1 month later showed early signs of fracture healing...

  16. Intravitreal bevacizumab for treatment of choroidal neovascularization associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2012-01-01

    Full Text Available A 12-year-old girl, diagnosed of osteogenesis imperfecta, presented with sudden visual loss in the left eye. Investigations revealed an active choroidal neovascular membrane. She underwent treatment with intravitreal Bevacizumab (1.25 mg/0.05 ml. Follow-up at 1 month revealed the development of lacquer crack running through the macula, underlying the fovea. The patient received two re-treatments at 1-month intervals, following which the choroidal neovascularization (CNV regressed completely. However, further progression of lacquer cracks was noted. At the last follow-up, 6 months following the last injection, the fundus remained stable and vision was maintained at 20/200. Considering the natural history of the disease and the increased risk of rupture of the Bruch′s membrane in such eyes, the possible complication of a lacquer crack developing must be borne in mind, before initiating treatment.

  17. In vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Kobayashi A

    2014-02-01

    Full Text Available Akira Kobayashi, Tomomi Higashide, Hideaki Yokogawa, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Objective: To report the in vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta (OI with special attention to the abnormality of Bowman's layer and sub-Bowman's fibrous structures (K-structures. Patients and methods: Two patients (67-year-old male and his 26-year-old son with OI type I were included in this study. Slit lamp biomicroscopic and in vivo laser confocal microscopic examinations were performed for both patients. Central corneal thickness and central endothelial cell density were also measured. Results: Although the corneas looked clear with normal endothelial density for both eyes in both patients, they were quite thin (386 µm oculus dexter (OD (the right eye and 384 µm oculus sinister (OS (the left eye in the father and 430 µm OD and 425 µm OS in the son. In both patients, slit lamp biomicroscopic and in vivo laser confocal microscopic examination showed similar results. Anterior corneal mosaics produced by rubbing the eyelid under fluorescein were completely absent in both eyes. In vivo laser confocal microscopy revealed an absent or atrophic Bowman's layer; a trace of a presumed Bowman's layer and/or basement membrane was barely visible with high intensity. Additionally, K-structures were completely absent in both eyes. Conclusion: The absence of K-structures and fluorescein anterior corneal mosaics strongly suggested an abnormality of Bowman's layer in these OI patients. Keywords: osteogenesis imperfecta, K-structure, confocal microscopy, Bowman's layer

  18. What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases.

    Science.gov (United States)

    Pepin, Melanie G; Byers, Peter H

    2015-12-01

    Non-accidental injury (NAI) is a major medical concern in the United States. One of the challenges in evaluation of children with unexplained fractures is that genetic forms of bone fragility are one of the differential diagnoses. Infants who present with fractures with mild forms of osteogenesis imperfecta (OI) (OI type I or OI type IV), the most common genetic form of bone disease leading to fractures might be missed if clinical evaluation alone is used to make the diagnosis. Diagnostic clinical features (blue sclera, dentinogenesis imperfecta, Wormian bones on X-rays or positive family history) may not be present or apparent at the age of evaluation. The evaluating clinician faces the decision about whether genetic testing is necessary in certain NAI cases. In this review, we outline clinical presentations of mild OI and review the history of genetic testing for OI in the NAI versus OI setting. We summarize our data of molecular testing in the Collagen Diagnostic Laboratory (CDL) from 2008 to 2014 where NAI was noted on the request for DNA sequencing of COL1A1 and COL1A2. We provide recommendations for molecular testing in the NAI versus OI setting. First, DNA sequencing of COL1A1, COL1A2, and IFITM5 simultaneously and duplication/deletion testing is recommended. If a causative variant is not identified, in the absence of a pathologic clinical phenotype, no additional gene testing is indicated. If a VUS is found, parental segregation studies are recommended.

  19. Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

    Science.gov (United States)

    Lindahl, Katarina; Åström, Eva; Rubin, Carl-Johan; Grigelioniene, Giedre; Malmgren, Barbro; Ljunggren, Östen; Kindmark, Andreas

    2015-01-01

    Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype–phenotype studies on >100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1- and α2-chains were associated with the absence of dentinogenesis imperfecta (P95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in >95% of an entire OI population. PMID:25944380

  20. Osteogenesis imperfecta type V: clinical and radiographic manifestations in mutation confirmed patients.

    Science.gov (United States)

    Kim, Ok-Hwa; Jin, Dong-Kyu; Kosaki, Keisuke; Kim, Jung-Wook; Cho, Sung Yoon; Yoo, Won Joon; Choi, In Ho; Nishimura, Gen; Ikegawa, Shiro; Cho, Tae-Joon

    2013-08-01

    Osteogenesis imperfecta (OI) type V is a specific OI phenotype with interosseous membrane calcification of the forearm and hyperplastic callus formation as typical features. The causative gene mutation for OI type V has been recently discovered. The purpose of this report is to review the clinical and radiographic characteristics of mutation confirmed OI type V in detail. Sixteen (nine familial and seven sporadic) patients were enrolled in the study. Blue sclera and dentinogenesis imperfecta were not evident in any patient. However, hypodontia in the permanent teeth, ectopic eruption, and short roots in molars were additionally observed in 11 patients. Of the radiographic abnormalities, cortical thickening and bony excrescence of interosseous margin of the ulna was the most common finding, followed by overgrowth of the olecranon and/or coronoid process of the ulna. Slender ribs and sloping of the posterior ribs with or without fractures were also a consistent finding. Hyperplastic callus was detected in 75% of patients and was commonly encountered at the femur. Heterotopic ossification in the muscles and tendon insertion sites were noted in four patients, which resulted in bony ankylosis or contracture of joints. The current study confirms common clinical and radiographic findings of OI type V and reports additional phenotypic information. These observations provide clues to recognize OI type V more promptly and guide to direct targeted molecular study. © 2013 Wiley Periodicals, Inc.

  1. Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta.

    Science.gov (United States)

    Lindahl, Katarina; Åström, Eva; Rubin, Carl-Johan; Grigelioniene, Giedre; Malmgren, Barbro; Ljunggren, Östen; Kindmark, Andreas

    2015-08-01

    Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on >100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1- and α2-chains were associated with the absence of dentinogenesis imperfecta (P95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in >95% of an entire OI population.

  2. A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse.

    Science.gov (United States)

    Aubin, Isabelle; Adams, Carolyn P; Opsahl, Sibylle; Septier, Dominique; Bishop, Colin E; Auge, Nathalie; Salvayre, Robert; Negre-Salvayre, Anne; Goldberg, Michel; Guénet, Jean-Louis; Poirier, Christophe

    2005-08-01

    The mouse mutation fragilitas ossium (fro) leads to a syndrome of severe osteogenesis and dentinogenesis imperfecta with no detectable collagen defect. Positional cloning of the locus identified a deletion in the gene encoding neutral sphingomyelin phosphodiesterase 3 (Smpd3) that led to complete loss of enzymatic activity. Our knowledge of SMPD3 function is consistent with the pathology observed in mutant mice and provides new insight into human pathologies.

  3. Molecular Consequences of the SERPINH1/HSP47 Mutation in the Dachshund Natural Model of Osteogenesis Imperfecta.

    OpenAIRE

    Lindert, Uschi; Weis, Mary Ann; Rai, Jyoti; Seeliger, Frank; Hausser, Ingrid; Leeb, Tosso; Eyre, David; Rohrbach, Marianne; Giunta, Cecilia

    2015-01-01

    Osteogenesis imperfecta (OI) is a heritable connective tissue disease characterized by bone fragility and increased risk of fractures. Up to now, mutations in at least 18 genes have been associated with dominant and recessive forms of OI that affect the production or post-translational processing of procollagen or alter bone homeostasis. Among those, SERPINH1 encoding heat shock protein 47 (HSP47), a chaperone exclusive for collagen folding in the ER, was identified to cause a severe form of ...

  4. Eleven years of experience with bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2012-12-01

    Full Text Available Jun Iwamoto,1 Yoshihiro Sato,2 Mitsuyoshi Uzawa,3 Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, 2Department of Neurology, Mitate Hospital, Fukuoka, 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanAbstract: We report the 11-year follow-up of a man with osteogenesis imperfecta type I who was treated with bisphosphonates and alfacalcidol. A 36-year-old Japanese man with osteogenesis imperfecta type I who had frequently experienced painful fragility fractures consulted our clinic because of chronic back pain. The patient had multiple morphometric vertebral fractures and a low bone mineral density (BMD at the lumbar spine. The patient was treated with cyclical etidronate 200 mg, for 2 weeks every 3 months, plus alfacalcidol 1 µg daily, for 2 years; and alendronate 5 mg daily or 35 mg weekly, plus alfacalcidol 1 µg daily for 9 years. After 11 years of treatment, BMD at the lumbar spine increased by 6.4%, following a 20.3% reduction in serum alkaline phosphatase. Serum calcium, phosphorus, and intact parathyroid hormone levels remained within the normal ranges. Three clinical fractures occurred at two ribs and the metacarpus, and two morphometric vertebral fractures occurred at the thoracic spine during the 11-year treatment period, but the patient experienced no adverse effects. Thus, the present case report shows the long-term outcome and safety of bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I.Keywords: etidronate, alendronate, fragility fracture, bone mineral density, osteogenesis imperfecta

  5. Cardiopulmonary dysfunction in the Osteogenesis imperfecta mouse model Aga2 and human patients are caused by bone-independent mechanisms

    OpenAIRE

    Thiele, Frank; Cohrs, Christian M.; Flor, Armando; Lisse, Thomas S.; Przemeck, Gerhard K. H.; Horsch, Marion; Schrewe, Anja; Gailus-Durner, Valerie; Ivandic, Boris; Katus, Hugo A.; Wurst, Wolfgang; Reisenberg, Catherine; Chaney, Hollis; Fuchs, Helmut; Hans, Wolfgang

    2012-01-01

    Osteogenesis imperfecta (OI) is an inherited connective tissue disorder with skeletal dysplasia of varying severity, predominantly caused by mutations in the collagen I genes (COL1A1/COL1A2). Extraskeletal findings such as cardiac and pulmonary complications are generally considered to be significant secondary features. Aga2, a murine model for human OI, was systemically analyzed in the German Mouse Clinic by means of in vivo and in vitro examinations of the cardiopulmonary system, to identif...

  6. Osteogenesis Imperfecta Model Peptides: Incorporation of Residues Replacing Gly within a Triple Helix Achieved by Renucleation and Local Flexibility

    OpenAIRE

    Xiao, Jianxi; Madhan, Balaraman; Li, Yingjie; Brodsky, Barbara; Baum, Jean

    2011-01-01

    Missense mutations, which replace one Gly with a larger residue in the repeating sequence of the type I collagen triple helix, lead to the hereditary bone disorder osteogenesis imperfecta (OI). Previous studies suggest that these mutations may interfere with triple-helix folding. NMR was used to investigate triple-helix formation in a series of model peptides where the residue replacing Gly, as well as the local sequence environment, was varied. NMR measurement of translational diffusion coef...

  7. Zoledronic acid treatment in an adult patient with Osteogenesis Imperfecta: A case report and review of the literature

    OpenAIRE

    Yazmalar, Levent; Batmaz, İbrahim; Dağlı, Abdullah Zübeyr; Hattapoğlu, Erkam; sarıyıldız, Mustafa Akif

    2014-01-01

    Osteogenesis Imperfecta (OI) is a rare heritable condition characterized by bone fragility and reduced bone mass. This pathology is characterized by disruption of biosynthesis of Type I collagen, and production of limited amount of defective and imperfect collagens. This causes decrease in bone mass of human body, bones become fragile and brittle, resulting in unreasonable multiple fractures. Other manifestations include hyperextensibility of the joints, blue sclera, hearing loss, short statu...

  8. Osteogenesis imperfecta

    Science.gov (United States)

    ... by a defect in the gene that produces type 1 collagen, an important building block of bone. There are ... Multiple bone fractures Early hearing loss ( deafness ) Because type I collagen is also found in ligaments, people with OI ...

  9. Distinctive tomographic abnormalities of the craniocervical region in a patient with osteogenesis imperfecta type IV B

    Energy Technology Data Exchange (ETDEWEB)

    Kaissi, Ali Al; Klaushofer, Klaus, E-mail: ali.alkaissi@osteologie.a [Ludwig Boltzmann Institute of Osteology, Vienna (Austria); Grill, Franz [Orthopaedic Hospital of Speising, Vienna (Austria). Paediatric Dept.

    2010-07-01

    Osteogenesis imperfecta is a clinically and genetically heterogeneous group of heritable disorders of connective tissue characterized by reduced bone mass (osteopenia) with associated bone fragility. The resulting skeletal manifestations are due to a generalized deficiency in the development of both membranous and endochondral bone and include markedly thin calvarium with delayed closure of the fontanelles and the sutures and excessive Wormian bone formation. Sillence et al. developed a classification system of OI subtypes: OI type I, which is characterised by blue sclerae; perinatal lethal OI type II, also known as congenital OI; OI type III, a progressively deforming subtype with normal sclera; and OI type IV, which is characterized by a normal sclera. Levin et al. have suggested that OI subtypes could be further divided into type A and B based on the absence or presence of dentinogenesis imperfecta. Basilar impression involves the upward (vertical) migration of the odontoid process into the foramen magnum with a depression in the cranium. Basilar impression is a developmental defect and refers to the infolding of the occipital condyles, an elevation of the clivus, and the posterior cranial fossa of the skull. The soft bones of the skull base allow for progressive infolding of the dysplastic clivus and translocation of the odontoid into the posterior fossa. The combination of platybasia and basilar impression can lead to severe distortion of the spinal cord and the anterior brain stem. The specific structures that can be involved include the upper cervical cord, medulla, pons, mid-brain, cerebellum, as well as the vertebrobasilar system. (author)

  10. A rare case of osteogenesis imperfecta combined with complete tooth loss.

    Science.gov (United States)

    Lu, Yanqin; Zhao, Fei; Ren, Xiuzhi; Li, Zhiliang; Yang, Xiaomeng; Han, Jinxiang

    2014-01-01

    Osteogenesis imperfecta (OI) is a heritable disorder of the connective tissue characterized by blue sclerae, osteoporosis and bone fragility. Dentinogenesis imperfecta type I is commonly seen in OI patients, but other dental impairments, such as tooth agenesis or complete tooth loss, are rarely reported for these patients. Here, we report the case of a 37-year-old female Chinese OI patient who experienced complete tooth loss before puberty. The patient has a family history of OI and her father has a history of tooth loss. She showed obvious OI phenotypes, including a dwarfed stature, blue sclerae, scoliosis, pigeon chest and a history of fractures. Tooth loss began at the age of 6 years and continued until complete tooth loss at 20 years; this occurred in the absence of dental decay, gum disease, accidents or drug usage. Radiological studies revealed osteoporosis of the lower limbs and an underdeveloped scapula. Type I collagen gene analysis identified a known c.2314G>A (p.Gly772Ser) substitution in the COL1A2 gene, which we suggest affects the interaction between type I collagen and extracellular matrix proteins, including cartilage oligomeric matrix protein, phosphophoryn and SPARC (secreted protein acidic and rich in cysteine). In silico prediction indicated a relatively mild effect of the mutation, so it is conceivable that the severity of the clinical phenotype may result from additional mutations in candidate genes responsible for abnormal dental phenotypes in this family. To our knowledge, this is the first report of an OI patient with a phenotype of complete tooth loss at a young age.

  11. AB069. Effect of osteogenesis imperfecta on children and their families

    Science.gov (United States)

    Dung, Vu Chi; Armstrong, Kate; Ngoc, Can Thi Bich; Thao, Bui Phuong; Khanh, Nguyen Ngoc; Trang, Nguyen Thu; Hoan, Nguyen Thi; Dat, Nguyen Phu; Munns, Craig

    2015-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous genetic disorder, with features that include increased bone fragility, pathological fractures, blue sclera, dentinogenesis imperfecta and conductive or mixed hearing loss. Clinical variability is wide from children with few fractures and normal stature to children with multiple fractures, long bone deformity, scoliosis and extreme short stature. Although there is no curative treatment, there are several therapeutic tools capable of improving the course of the condition and patient quality of life. We aim to evaluate the effect of OI on the well-being of children with the disorder and their families through a family-centered questionnaire. Sixty children with OI from the Vietnam National Hospital of Pediatrics and/or their parent(s), who attended the first annual family support group in 2011, completed a child and parent questionnaire. Sixty patients participated, 26 female and 34 male. The median age was 6.0 years [interquartile range (IQR), 0.25-18 years]. Of these, 36 (60%) had dentinogenesis imperfect and 23 (38.3%) had a scoliosis. The median number of fractures was 6.0 (IQR 0-30) and median number of hospitalizations due to OI was 5.0 (IQR 0-30). Among patients of school age, 9 (15%) could not go to school due to OI. Almost all parents (93.7%) worried about school social communication of the patients. Among these parents, 100% fear of inferiority with friends and 98.3% fear of broken bones. Most parents (76.2%) were significantly concerned about their child’s health. The parents’ themselves reported psychological concerns, with feelings of desperation (58.4%), anxiety (81.7%) and depression (56.7%). OI appeared to have a significant deleterious effect on the life of the patients and their families. These data provide a baseline from which to evaluate the effectiveness of interventions to improve the medical and psychological needs of this cohort and their families.

  12. Osteogenesis Imperfecta Presented with Vertebral Fractures After Pregnancy and Treatment with Cyclical Etidronate: A Case Report

    Directory of Open Access Journals (Sweden)

    Cengiz Bahadır

    2005-06-01

    Full Text Available Osteogenesis imperfecta(OI is a kongenital skelatal disorder charecterized by low bone mass and increased bone fragility. Fractures due to increased bone fragility occur frequently in childhood and decrease with age. Only a few studies have been reported regarding the teratment of adult patients with OI. Our case was a 27 year old woman with severe back pain occured when she was lifting her baby. The patient had experienced multiple fractures of long bones by her childhood. Compression fractures at thoracal 10 and 12 vertebrae were found on Magnetic Resonance Imaging . Dual energy X-ray absorptiomety(DEXA showed that markedly decreased bone mineral density(BMD both at lumbar spine and femur. The diagnosis of OI type I was based on the findings of blue sclera, antecedent multiple fractures, positive family history and low bone mass. Patient was treated with cyclical etidronate, calcium and Vitamin D over a year. No new fractures were observed during the treatment period. Lomber and proximal femur BMD’s were found to be significantly increased at the end of one year. Our case was treated succesfully with combination of cyclical etidronate, calcium and vitamin D. Etidronate would seem to be available treatment for adult patients with OI. However, the best treatment regimen and the long-term outcomes of etidronate therapy are unknown.

  13. Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice☆

    Science.gov (United States)

    Vanleene, Maximilien; Porter, Alexandra; Guillot, Pascale-Valerie; Boyde, Alan; Oyen, Michelle; Shefelbine, Sandra

    2012-01-01

    Bone is a complex material with a hierarchical multi-scale organization from the molecule to the organ scale. The genetic bone disease, osteogenesis imperfecta, is primarily caused by mutations in the collagen type I genes, resulting in bone fragility. Because the basis of the disease is molecular with ramifications at the whole bone level, it provides a platform for investigating the relationship between structure, composition, and mechanics throughout the hierarchy. Prior studies have individually shown that OI leads to: 1. increased bone mineralization, 2. decreased elastic modulus, and 3. smaller apatite crystal size. However, these have not been studied together and the mechanism for how mineral structure influences tissue mechanics has not been identified. This lack of understanding inhibits the development of more accurate models and therapies. To address this research gap, we used a mouse model of the disease (oim) to measure these outcomes together in order to propose an underlying mechanism for the changes in properties. Our main finding was that despite increased mineralization, oim bones have lower stiffness that may result from the poorly organized mineral matrix with significantly smaller, highly packed and disoriented apatite crystals. Using a composite framework, we interpret the lower oim bone matrix elasticity observed as the result of a change in the aspect ratio of apatite crystals and a disruption of the crystal connectivity. PMID:22449447

  14. A fracture risk assessment model of the femur in children with osteogenesis imperfecta (OI) during gait.

    Science.gov (United States)

    Fritz, Jessica M; Guan, Yabo; Wang, Mei; Smith, Peter A; Harris, Gerald F

    2009-11-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder characterized by skeletal deformities and increased bone fragility. There is currently no established clinical method for quantifying fracture risk in OI patients. This study begins the development of a patient-specific model for femur fracture risk assessment and prediction based on individuals' gait analysis data, bone geometry from imaging and material properties from nanoindentation (Young's modulus=19 GPa, Poisson's ratio=0.3). Finite element models of the femur were developed to assess fracture risk of the femur in a pediatric patient with OI type I. Kinetic data from clinical gait analysis was used to prescribe loading conditions on the femoral head and condyles along with muscle forces on the bone's surface. von Mises stresses were analyzed against a fracture strength of 115 MPa. The patient with OI whose femur was modeled showed no risk of femoral fracture during normal gait. The highest stress levels occurred during the mid-stance and loading responses phases of gait. The location of high stress migrated throughout the femoral diaphysis across the gait cycle. Maximum femoral stress levels occurred during the gait cycle phases associated with the highest loading. The fracture risk (fracture strength/von Mises stress), however, was low. This study provides a relevant method for combining functional activity, material property and analytical methods to improve patient monitoring.

  15. Raloxifene reduces skeletal fractures in an animal model of osteogenesis imperfecta.

    Science.gov (United States)

    Berman, Alycia G; Wallace, Joseph M; Bart, Zachary R; Allen, Matthew R

    2016-01-01

    Osteogenesis imperfecta (OI) is a genetic disease of Type I collagen and collagen-associated pathways that results in brittle bone behavior characterized by fracture and reduced mechanical properties. Based on previous work in our laboratory showing that raloxifene (RAL) can significantly improve bone mechanical properties through non-cellular mechanisms, we hypothesized that raloxifene would improve the mechanical properties of OI bone. In experiment 1, tibiae from female wild type (WT) and homozygous oim mice were subjected to in vitro soaking in RAL followed by mechanical tests. RAL soaking resulted in significantly higher post-yield displacement (+75% in WT, +472% in oim; pled to significantly higher DXA-based BMD (pTV in both WT and oim animals compared to those treated with VEH. Fracture toughness of the femora was lower in oim mice compared to WT and improved with RAL in both genotypes. These results suggest that raloxifene reduces the incidence of fracture in this mouse model of oim. Furthermore, they suggest that raloxifene's effects may be the result of both cellular (increased bone mass) and non-cellular (presumably changes in hydration) mechanisms, raising the possibility of using raloxifene, or related compounds, as a new approach for treating bone fragility associated with OI. PMID:26707242

  16. Introduction of a new standardized assessment score of spine morphology in osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Koerber, F.; Schulze Uphoff, U.; Koerber, S.; Maintz, D. [Koeln Univ. (Germany). Dept. of Radiology; Schoenau, E.; Semler, O. [Koeln Univ. (Germany). Children' s Hospital

    2012-08-15

    Purpose: Osteogenesis imperfecta (OI) is a rare hereditary disease leading to multiple bone deformities and fractures. In the absence of causal therapy, a symptomatic approach is based on treatment with bisphosphonates and physiotherapy. The clinical and radiological manifestations vary. Therefore, standardization and quantification for an objective comparison, especially during therapy, are required. In this paper, radiological changes of the spine are quantified according to their clinical relevance to define a scoring system that transfers the morphological changes into a single value representing the severity of the disease. Materials and Methods: 268 lateral spine X-rays of 95 patients with OI (median age 5.6 years) were assessed. The findings were classified based on their clinical relevance. Results: The three criteria, vertebral compression, thoracolumbar kyphosis and deformity type, were quantified in a new grading system. Based on this, a 'severity classification' (1 to 5) was defined with implications for diagnostics and treatment. A mathematical formula that takes into account the three criteria and their correlations to clinical relevance, resulting in a 'severity score', was developed. Conclusion: 'Severity classification' and 'severity score' introduce a new concept for a standardized evaluation of spine X-rays in patients with OI. For both scientific and routine purposes, it provides the user with a simple and easy-to-handle tool for assessing and comparing different stages of severity prior to and during therapy with detailed accuracy. (orig.)

  17. Identification of a novel heterozygous mutation in exon 50 of the COL1A1 gene causing osteogenesis imperfecta

    OpenAIRE

    Aftab, S A S; Reddy, N.; Owen, N L; POLLITT, R.; Harte, A.; McTernan, P G; Tripathi, G.; Barber, T M

    2013-01-01

    Summary A 19-year-old woman was diagnosed with osteogenesis imperfecta (OI). She had sustained numerous low-trauma fractures throughout her childhood, including a recent pelvic fracture (superior and inferior ramus) following a low-impact fall. She had the classical blue sclerae, and dual energy X-ray absorptiometry (DEXA) bone scanning confirmed low bone mass for her age in the lumbar spine (Z-score was −2.6). However, despite these classical clinical features, the diagnosis of OI had not be...

  18. Associação entre artrite idiopática juvenil e osteogenesis imperfecta: relato de caso

    Directory of Open Access Journals (Sweden)

    Blanca Elena Rios Gomes Bica

    2013-12-01

    Full Text Available Os autores relatam o caso de uma paciente de 53 anos que apresenta uma rara associação entre artrite idiopática juvenil (AIJ e osteogenesis imperfecta (OI, com acometimento poliarticular, incluindo a articulação temporomandibular. Apresentam uma revisão da literatura e uma discussão dos aspectos radiológicos do acometimento da referida articulação. Não foram encontrados relatos de casos com semelhante associação de doenças na literatura especializada.

  19. Deep tissue single cell MSC ablation using a fiber laser source to evaluate therapeutic potential in osteogenesis imperfecta

    Science.gov (United States)

    Tehrani, Kayvan F.; Pendleton, Emily G.; Lin, Charles P.; Mortensen, Luke J.

    2016-04-01

    Osteogenesis imperfecta (OI) is a currently uncurable disease where a mutation in collagen type I yields brittle bones. One potential therapy is transplantation of mesenchymal stem cells (MSCs), but controlling and enhancing transplanted cell survival has proven challenging. Therefore, we use a 2- photon imaging system to study individual transplanted cells in the living bone marrow. We ablated cells deep in the bone marrow and observed minimal collateral damage to surrounding tissue. Future work will evaluate the local impact of transplanted MSCs on bone deposition in vivo.

  20. Anestesia venosa total em paciente portador de Osteogênesis imperfecta: relato de caso Anestesia venosa total en paciente portador de Osteogénesis imperfecta: relato de caso Total intravenous anesthesia in Osteogenesis imperfecta patient: case report

    Directory of Open Access Journals (Sweden)

    José Francisco Nunes Pereira das Neves

    2004-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A Osteogênesis Imperfecta é uma doença genética rara do tecido conjuntivo, com prevalência de 1/10000, que primariamente envolve a ossificação endocondral, resultando em ossos frágeis, múltiplas fraturas e deformidades esqueléticas. O objetivo desse artigo foi relatar um caso de paciente portador de Osteogenesis Imperfecta, submetido à anestesia venosa total para tratamento cirúrgico de fratura de fêmur. RELATO DO CASO: Paciente do sexo masculino, 15 anos, 41 kg, 140 cm, com história de Osteogênesis Imperfecta e cardiopatia, programado para tratamento cirúrgico de fratura do fêmur. Na sala de operação foi monitorizado com ECG, FC, PANI e SpO2 e submetido à anestesia geral venosa total com propofol, alfentanil e cisatracúrio. Após IOT, foi acrescentada monitorização da P ET CO2 e da temperatura esofágica. No período intra-operatório e na sala de recuperação pós-anestésica não apresentou complicações. Teve alta hospitalar no 5º dia de pós-operatório. CONCLUSÕES: O presente relato mostrou boa evolução intra e pós-operatória de paciente com Osteogênesis Imperfecta submetido à anestesia geral venosa total. A complexidade da doença mostrou a necessidade de avaliação e monitorização adequada pelo anestesiologista.JUSTIFICATIVA Y OBJETIVOS: La Osteogénesis Imperfecta es una rara enfermedad genética del tejido conjuntivo, con prevalencia de 1/10000, que primariamente envuelve la osificación endocondral, resultando en huesos frágiles, múltiplas fracturas e deformidades esqueléticas. El objetivo de ese artículo fue relatar un caso de paciente portador de Osteogénesis Imperfecta, sometido a anestesia venosa total para tratamiento quirúrgico de fractura de fémur. RELATO DEL CASO: Paciente del sexo masculino, 15 años, 41 kg, 140 cm, con historia de Osteogénesis Imperfecta y cardiopatía, programado para tratamiento quirúrgico de fractura del fémur. En la sala de operaci

  1. Unique micro- and nano-scale mineralization pattern of human osteogenesis imperfecta type VI bone.

    Science.gov (United States)

    Fratzl-Zelman, Nadja; Schmidt, Ingo; Roschger, Paul; Roschger, Andreas; Glorieux, Francis H; Klaushofer, Klaus; Wagermaier, Wolfgang; Rauch, Frank; Fratzl, Peter

    2015-04-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of inheritable connective tissue disorders characterized by mutation in genes involved in collagen synthesis and leading to increased bone fragility, low bone mass, impaired bone material properties and abnormally high bone matrix mineralization. Recessive OI type VI is caused by mutation in SERPINF1 leading to a loss-of-function of pigment epithelium-derived factor (PEDF) a collagen-binding protein with potent antiangiogenic activity. Affected patients develop a severe OI phenotype with a striking histological characteristic, rare in other OI types, of an excess of osteoid tissue and prolonged mineralization lag time. To get insights into matrix mineralization, we evaluated biopsies from 9 affected children by quantitative and by high-resolution backscattered electron imaging and assessed bone mineralization density distribution. Thickness, shape and arrangement of mineral particles were measured in a subset of 4 patients by synchrotron small angle X-ray scattering. Typical calcium content in the bone matrix was found to be increased compared to controls, even exceeding values found previously in OI patients with collagen-gene mutations. A main characteristic however, is the coexistence of this highly mineralized bone matrix with seams showing abnormally low mineral content. Atypical collagen fibril organization was found in the perilacunar region of young osteocytes, suggesting a disturbance in the early steps of mineralization. These observations are consistent with the presence of a heterogeneous population of mineral particles with unusual size, shape and arrangement, especially in the region with lower mineral content. The majority of the particles in the highly mineralized bone areas were less disorganized, but smaller and more densely packed than in controls and in previously measured OI patients. These data suggest that the lack of PEDF impairs a proper osteoblast-osteocyte transition and consequently

  2. Copy number variants in association with type 1 collagenopathy: Atypical osteogenesis imperfecta.

    Science.gov (United States)

    Balasubramanian, Meena; Cartwright, Ashley; Smith, Kath; Arundel, Paul; Bishop, Nicholas J

    2016-02-01

    We report a sibling-pair and a 4-year old child from two families with an atypical presentation in Osteogenesis imperfecta (OI). In the sib-pair, the older sibling initially came to medical attention due to a fracture history (Patient 1) and she was shown to have a COL1A2 mutation. In addition, she also had developmental delay, facial dysmorphism, and a history of frequent infections which led to a search for an alternate diagnosis. ArrayCGH revealed a 4.3 Mb duplication on chromosome 19q13.42q13.43, which was confirmed by FISH analysis. On further familial analysis, the younger sibling who had no previous fracture history was also found to have the COL1A2 mutation and tested positive for the 19q13.42q13.43 duplication (Patient 2). The 19q13 duplication appears to be the cause of intellectual disability in these siblings but given that this is a chromosomal duplication, it is still possible that there is an as yet unidentified cause that may account for the combined phenotype in this family. Patient 3 was a 4-year old child presenting with a femoral fracture, blue sclerae, developmental delay, and joint hypermobility. Genetic analyses confirmed a COL1A2 mutation but also revealed an 8.8 Mb deletion of 11q24.2q25, confirmed by G-band chromosome analysis. We discuss the differing phenotypes in patients presenting with atypical OI and stress the need to consider ancillary investigations in individuals presenting with heterogeneous phenotypic symptoms, not entirely attributable to OI. PMID:26471105

  3. Tracing the pathway between mutation and phenotype in osteogenesis imperfecta: Isolation of mineralization-specific genes

    Energy Technology Data Exchange (ETDEWEB)

    Culbert, A.A.; Wallis, G.A.; Kadler, K.E. [Univ. of Manchester (United Kingdom)

    1996-05-03

    The brittleness of bone in people with lethal (type II) osteogenesis imperfecta, a heritable disorder caused by mutations in the type I collagen genes, arises from the deposition of abnormal collagen in the bone matrix. The inability of the abnormal collagen to participate in mineralization may be caused by its failure to interact with other bone proteins. Here, we have designed a strategy to isolate the genes important for mineralization of collagen during bone formation. Cells isolated from 16-day embryonic chick calvaria and seeded post-confluence in culture deposited a mineralized matrix over a period of 2 weeks. Chick skin fibroblasts seeded and cultured under the same conditions did not mineralize. Using RT-PCR, we prepared short cDNAs ({approximately}300 bp) corresponding to the 3{prime} ends of mRNA from fibroblasts and separately from the mineralizing calvarial cells. Subtractive cDNA hybridization generated a pool of cDNAs that were specific to mineralizing calvarial cells but not to fibroblasts. Screening of 100,000 plaques of a chick bone ZAP Express cDNA library with this pool of mineralizing-specific cDNAs identified ten clones which comprised full-length cDNAs for the bone proteins osteopontin (eight of the ten positives), bone sialoprotein II (one of the ten positives), and cystatin (one of the ten positives). cDNAs for type I collagen, fibronectin, alkaline phosphatase, house-keeping genes, and other genes expressed in fibroblasts were not identified in this preliminary screen. The pool of short cDNAs is likely to comprise cDNAs for further bone-specific genes and will be used to screen the entire bone cDNA library of 4.2 million clones. 30 refs., 4 figs.

  4. Strontium Ranelate Reduces the Fracture Incidence in a Growing Mouse Model of Osteogenesis Imperfecta.

    Science.gov (United States)

    Shi, Changgui; Hu, Bo; Guo, Lei; Cao, Peng; Tian, Ye; Ma, Jun; Chen, Yuanyuan; Wu, Huiqiao; Hu, Jinquan; Deng, Lianfu; Zhang, Ying; Yuan, Wen

    2016-05-01

    Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by brittle bones with increased fracture risk. Although current treatment options to improve bone strength in OI focus on antiresorptive bisphosphonates, controlled clinical trials suggest they have an equivocal effect on reducing fracture risk. Strontium ranelate (SrR) is a promising therapy with a dual mode of action that is capable of simultaneously maintaining bone formation and reducing bone resorption, and may be beneficial for the treatment of OI. In this study, SrR therapy was investigated to assess its effects on fracture frequency and bone mass and strength in an animal model of OI, the oim/oim mouse. Three-week-old oim/oim and wt/wt mice were treated with either SrR or vehicle (Veh) for 11 weeks. After treatment, the average number of fractures sustained by SrR-treated oim/oim mice was significantly reduced compared to Veh-treated oim/oim mice. Micro-computed tomographic (μCT) analyses of femurs showed that both trabecular and cortical bone mass were significantly improved with SrR treatment in both genotypes. SrR significantly inhibited bone resorption, whereas bone formation indices were maintained. Biomechanical testing revealed improved bone structural properties in both oim/oim and wild-type (wt/wt) mice under the treatment, whereas no significant effects on bone brittleness and material quality were observed. In conclusion, SrR was able to effectively reduce fractures in oim/oim mice by improving bone mass and strength and thus represents a potential therapy for the treatment of pediatric OI. © 2015 American Society for Bone and Mineral Research. PMID:26679066

  5. Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta.

    Science.gov (United States)

    Orioli, I M; Castilla, E E; Scarano, G; Mastroiacovo, P

    1995-11-01

    The paternal ages of nonfamilial cases of achondroplasia (AC) (n = 78), thanatophoric dysplasia (TD) (n = 64), and osteogenesis imperfecta (OI) (n = 106), were compared with those of matched controls, from an Italian Indagine Policentrica Italiana sulle Malformazioni Congenite and a South American Estudio Colaborativo Latinoamericano de Malformaciones Congénitas series. The degree of paternal age effect on the origin of these dominant mutations differed among the three conditions. Mean paternal age was highly elevated in AC, 36.30 +/- 6.74 years in the IPIMC, and 37.19 +/- 10.53 years in the ECLAMC; less consistently elevated in TD, 33.60 +/- 7.08 years in the IPIMC, and 36.41 +/- 9.38 years in the ECLAMC; and only slightly elevated in OI in the ECLAMC, 31.15 +/- 9.25 years, but not in the IPIMC, 32.26 +/- 6.07 years. Increased maternal age or birth order in these conditions disappeared when corrected for paternal age. Approximately 50% of AC and TD cases, and only 30% of OI cases, were born to fathers above age 35 years. For AC and TD, the increase in relative incidence with paternal age fitted an exponential curve. The variability of paternal age effect in these new mutations could be due, among other reasons, to the high proportion of germ-line mosaicism in OI parents, or to the localization of the AC gene, mapped to the 4p16.3 region, in the neighborhood of an unstable DNA area.

  6. Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Orioli, I.M. [Universidade Federal do Rio de Janeiro (Brazil); Castilla, E.E. [Centro de Educacion Medica e Investigacion Clinica, Buenos Aires (Argentina); Scarano, G.; Mastroiacovo, P. [Universita Cattolica, Rome (Italy)

    1995-11-06

    The paternal ages of nonfamilial cases of achondroplasia (AC) (n = 78), thanatophoric dysplasia (TD) (n = 64), and osteogenesis imperfecta (OI) (n = 106), were compared with those of matched controls, from an Italian Indagine Policentrica Italiana sulle Malformazioni Congenite (IPIMC) and a South American Estudio Colaborativo Latinoamericano de Malformaciones Congenitas (ECLAMC) series. The degree of paternal age effect on the origin of these dominant mutations differed among the three conditions. Mean paternal age was highly elevated in AC, 36.30 {plus_minus} 6.74 years in the IPIMC, and 37.19 {plus_minus} 10.53 years in the ECLAMC; less consistently elevated in TD, 33.60 {plus_minus} 7.08 years in the IPIMC, and 36.41 {plus_minus} 9.38 years in the ECLAMC; and only slightly elevated in OI in the ECLAMC, 31.15 {plus_minus} 9.25 years, but not in the IPIMC, 32.26 {plus_minus} 6.07 years. Increased maternal age or birth order in these conditions disappeared when corrected for paternal age. Approximately 50% of AC and TD cases, and only 30% of OI cases, were born to fathers above age 35 years. For AC and TD, the increase in relative incidence with paternal age fitted an exponential curve. The variability of paternal age effect in these new mutations could be due, among other reasons, to the high proportion of germ-line mosaicism in OI parents, or to the localization of the AC gene, mapped to the 4p16.3 region, in the neighborhood of an unstable DNA area. 28 refs., 1 fig., 6 tabs.

  7. Skeletal dysplasia in perinatal lethal osteogenesis imperfecta. A complex disorder of endochondral and intramembranous ossification.

    Science.gov (United States)

    Marion, M J; Gannon, F H; Fallon, M D; Mennuti, M T; Lodato, R F; Kaplan, F S

    1993-08-01

    Osteogenesis imperfecta (OI) Type II is a rare heritable disorder of bone matrix that results in catastrophic congenital skeletal dysplasia. Two cases of OI Type II had symmetric rhizomelic skeletal dysplasia apparent on ultrasound at 16 and 20 weeks' gestation. Histologic and histochemical studies performed on skeletal tissue from fetal autopsies showed the following: (1) abnormal growth plate tissue characterized by failure of formation of primary bony spongiosa; (2) persistence of calcified cartilage bars in the diaphysis; (3) metaphyseal microfractures; (4) abundant cartilaginous fracture callus; (5) absence of bony callus; (6) failure of formation of intramembranous cortical diaphyseal bone; (7) angulation of long bones in portions of the metadiaphyses bordered by fracture callus; and (8) mechanical failure of the perichondral ring of LaCroix with a normal fibrous ossification groove of Ranvier. These findings suggest that skeletal dysplasia in OI Type II results from the action of muscular forces on a skeleton weakened by a complex disorder of endochondral and intramembranous ossification. The paucity of primary metaphyseal trabeculae and subperiosteal cortical bone leads to pathologic fractures of the immature fiber bone and an imperfect attempt at fracture repair. Angulation and shortening of long bones occurs between numerous sites of focal endochondral fracture callus. Mechanical failure of the fibrous perichondral ring leads to further collapse and shortening without obvious functional impairment of the fibrous ossification groove. Perinatal lethal OI provides insight into how a molecular disorder predominantly of Type I collagen metabolism results in pathology of numerous tissues, leading to severe skeletal dysplasia without primarily affecting chondrogenesis. PMID:8339500

  8. Pregnancy complicated by a severe form of foetal osteogenesis imperfecta in a 17-year-old primigravida: case report and overview of literature.

    Science.gov (United States)

    Madu, Anthony Emeka; Olamijulo, Joseph Ayodeji

    2013-05-01

    Abstract Osteogenesis imperfecta (OI) is an important inheritable thanetrophic disorder with wide ranging variable implications and prognosis for babies in utero and those who survive the perinatal period. The diagnosis of the severe forms can be readily made but some forms of the disease are known to go unrecognised until childhood.

  9. Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen

    NARCIS (Netherlands)

    Schwarze, Ulrike; Cundy, Tim; Pyott, Shawna M.; Christiansen, Helena E.; Hegde, Madhuri R.; Bank, Ruud A.; Pals, Gerard; Ankala, Arunkanth; Conneely, Karen; Seaver, Laurie; Yandow, Suzanne M.; Raney, Ellen; Babovic-Vuksanovic, Dusica; Stoler, Joan; Ben-Neriah, Ziva; Segel, Reeval; Lieberman, Sari; Siderius, Liesbeth; Al-Aqeel, Aida; Hannibal, Mark; Hudgins, Louanne; McPherson, Elizabeth; Clemens, Michele; Sussman, Michael D.; Steiner, Robert D.; Mahan, John; Smith, Rosemarie; Anyane-Yeboa, Kwame; Wynn, Julia; Chong, Karen; Uster, Tami; Aftimos, Salim; Sutton, V. Reid; Davis, Elaine C.; Kim, Lammy S.; Weis, Mary Ann; Eyre, David; Byers, Peter H.

    2013-01-01

    Although biallelic mutations in non-collagen genes account for 10 of individuals with osteogenesis imperfecta, the characterization of these genes has identified new pathways and potential interventions that could benefit even those with mutations in type I collagen genes. We identified mutations in

  10. Molecular Mechanism of Osteogenesis Imperfecta%成骨不全的分子机制

    Institute of Scientific and Technical Information of China (English)

    徐超; 韩金祥; 鲁艳芹

    2012-01-01

    成骨不全是一类临床表现为骨质脆弱、易骨折等特征的罕见遗传性疾病.绝大多数(90%以上)显性患者发病系由Ⅰ型前胶原α链COLlA1和COLl A2基因突变引起胶原合成量不足,或结构改变.少数隐性患者发病为其他相关基因突变导致胶原翻译后过度修饰、折叠、装配和分泌过程异常.本文就成骨不全发病的遗传学及分子生物学机制作一综述.%Osteogenesis imperfecta ( OI) is a kind of rare genetic disease characterized by increased bone fragility and easy to fracture. Clinical symptoms include frequent bone fracture, short stature, blue sclera, dentinogenesis imperfecta and hearing loss. OI is a heterogeneous disease; its patterns of inheritance are predominated by autosomal dominant, but the autosomal recessive inheritance is rare. Patterns of clinical phenotype vary from mild to perinatal lethal one. Based on traditional silence type system of I-IV, type V-XII has been described till now. Ten different genes have been reported to cause OI. The genetic cause for type V is still unknown. COLlAl and C0LIA2, which encode the a chains of type I procollagen, are the main OI-related genes and relate to autosomal dominant OI. Mutations in these two genes lead to 90% of OI cases. The vast majority mutations of COLlAl and C0L1A2 are Gly substitution. In addition, eight different gene defect associated with recessive genetic OI have been reported in recent years. CRTAP, LEPREX and PPIB encode CRTAP, P3H1 and CyPB, respectively. They assemble into 3-hydroxylation complex which participates in posttranslational modification of collagen I. As chaperones, FKBP65 encoded by FKBP10 and HSP47 encoded by SERPINHl take part in the process of folding and assembling of collagen type I. OSX is a kind of transcription factor, which might be expected to play an important role in osteoblast differentiation. SERPINFl is close contact with metabolic disorder of bone. BMP1 defect is reported to cause

  11. Benefit of infusions with ibandronate treatment in children with osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    LI Mei; MENG Xun-wu; XU Ling; XIA Wei-bo; XING Xiao-ping; YU Wei; HU Ying-ying; JIANG Yan; WANG Ou; LIU Hai-juan; HAN Lan-wen

    2011-01-01

    Background Osteogenesis imperfecta (OI) is a rare bone disease and its effective treatment is relatively deficient. We tried to assess the effects of new bisphosphonate, ibandronate on children with OI.Methods In this open-label, prospective, controlled study, 30 children with OI were enrolled. They received either infusions of ibandronate (2 mg) in every three months or oral calcitriol 0.25 μg daily for 24 months. All patients took 500 mg calcium plus 200 U vitamin D daily together. The endpoints were the change of annual new fracture rate (observed by case history and X ray films of spine), bone mineral density (BMD, measured by dual energy X-ray absortiometry), serum concentration of carboxy-telopeptide cross-links of type Ⅰ collagen (CTX, bone resorption marker) and alkaline phosphatase (ALP, bone formation marker) during the follow-up.Results After the cyclic infusions of ibandronate, the annual new fracture rate was significantly decreased from 1.9 to 0.13 time, obviously lower than that of calcitriol group, which decreased from 1.8 to 1.0 time after the treatment (P <0.001).The significant increase of BMD at the lumbar spine, femoral neck, trochanter, total hip was found in the group of ibandronate by 59.0%, 42.0%, 47.5% and 36.6% in time dependent manner (compared with the baseline, P <0.001). The increase of BMD in ibandronate group was greater than that of calcitriol group (P <0.001). The concentrations of ALP and CTX were obviously decreased in ibandronate group, and the reduction of CTX was more significant than that of ALP (P <0.001). The tolerance of the children to ibandronate was quite well. Mild fever and muscle pain were found in 9 cases within 1-3 days after the first infusion of ibandronate, which could relieve after 1-2 days without special management.Conclusions The benefits of cyclic infusions of ibandronate to children with OI are significant because ibandronate could significantly reduce annual bone fracture rate

  12. First mouse model for combined osteogenesis imperfecta and Ehlers-Danlos syndrome.

    Science.gov (United States)

    Chen, Frieda; Guo, Ruolin; Itoh, Shousaku; Moreno, Luisa; Rosenthal, Esther; Zappitelli, Tanya; Zirngibl, Ralph A; Flenniken, Ann; Cole, William; Grynpas, Marc; Osborne, Lucy R; Vogel, Wolfgang; Adamson, Lee; Rossant, Janet; Aubin, Jane E

    2014-06-01

    By using a genome-wide N-ethyl-N-nitrosourea (ENU)-induced dominant mutagenesis screen in mice, a founder with low bone mineral density (BMD) was identified. Mapping and sequencing revealed a T to C transition in a splice donor of the collagen alpha1 type I (Col1a1) gene, resulting in the skipping of exon 9 and a predicted 18-amino acid deletion within the N-terminal region of the triple helical domain of Col1a1. Col1a1(Jrt) /+ mice were smaller in size, had lower BMD associated with decreased bone volume/tissue volume (BV/TV) and reduced trabecular number, and furthermore exhibited mechanically weak, brittle, fracture-prone bones, a hallmark of osteogenesis imperfecta (OI). Several markers of osteoblast differentiation were upregulated in mutant bone, and histomorphometry showed that the proportion of trabecular bone surfaces covered by activated osteoblasts (Ob.S/BS and N.Ob/BS) was elevated, but bone surfaces undergoing resorption (Oc.S/BS and N.Oc/BS) were not. The number of bone marrow stromal osteoprogenitors (CFU-ALP) was unaffected, but mineralization was decreased in cultures from young Col1a1(Jrt) /+ versus +/+ mice. Total collagen and type I collagen content of matrices deposited by Col1a1(Jrt) /+ dermal fibroblasts in culture was ∼40% and 30%, respectively, that of +/+ cells, suggesting that mutant collagen chains exerted a dominant negative effect on type I collagen biosynthesis. Mutant collagen fibrils were also markedly smaller in diameter than +/+ fibrils in bone, tendon, and extracellular matrices deposited by dermal fibroblasts in vitro. Col1a1(Jrt) /+ mice also exhibited traits associated with Ehlers-Danlos syndrome (EDS): Their skin had reduced tensile properties, tail tendon appeared more frayed, and a third of the young adult mice had noticeable curvature of the spine. Col1a1(Jrt) /+ is the first reported model of combined OI/EDS and will be useful for exploring aspects of OI and EDS pathophysiology and treatment.

  13. Osteogenesis imperfecta combined with osteonecrosis of the femoral head:1 case report%成骨不全症合并股骨头坏死一例

    Institute of Scientific and Technical Information of China (English)

    吴李菲; 蔡贤华; 黄卫兵; 夏平光

    2014-01-01

    Osteogenesis imperfecta ( OI ) is a genetically and clinically heterogeneous disorder of the bone and connective tissues characterized by osteoporosis, fragile bones, hyperextensible joints, dentinogenesis imperfecta, bluish coloration of the sclerae, and adult-onset hearing loss. One case of young patient treated in our department was diagnosed with OI and osteonecrosis of the femoral head ( ONFH ) by medical history, family history and imagingdata. After the treatment of percutaneous decompression procedure, his imaging data and the Harris score of both hip joints conifrmed the surgery was effective.

  14. Multi-element analysis of bone from the osteogenesis imperfecta model (OIM) mouse using thermal and fast neutron activation analysis

    International Nuclear Information System (INIS)

    Osteogenesis imperfecta (OI) is a heritable osteoporotic bone disease, due to defects in either type I procollagen genes (COL1A1 or COL1A2), resulting in abnormal and/or reduced levels of type I procollagen and alterations in bone mineralization. Our long term objectives are to evaluate the impact of proα1(I) and proα2(I) collagen mutations and the role of the genetic background on bone mineralization. Tibias from wildtype, heterozygous (oim/+), and homozygous (oim/oim) animals were subjected to instrumental neutron activation analysis (INAA) to measure F, P, Na, Mg, Cl, Ca, K, and Zn using the University of Missouri Research Reactor (MURR) pneumatic-tube irradiation facility. (author)

  15. NOVEL SPLICING MUTATION OF COL1A1 GENE CAUSING OSTEOGENESIS IMPERFECTA TYPE I IN CHINESE PEDIGREE

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-lin; GU Ming-min; CUI Bing; LI Xi-hua; LU Zhen-yu; WANG Zhu-gang; YUAN Wen-tao; SONG Huai-dong

    2007-01-01

    Objective To detect the peculiar mutation in a Chinese family with osteogenesis imperfecta,COL1A1 and COL1A2 being analysed. Methods A genome screen was undertaken covering COL1A1 at 17q21-22 and COL1A2 at 7q22.1. The Linkage ( Version 5.1 ) was used for 2-point analysis. DNA sequencing was used to screen and identify the mutation. Results A linkage to the markers on chromosome 17q21-22 was observed. Sequence analysis of COL1A1 revealed a splicing mutation ( IVS8-2A > G) that converted the 3' end of intron 8 from AG to GG. Conclusion This mutation ( IVS 8-2A > G) is novel, and has not yet been registered in the Human Type Ⅰ and Type Ⅲ Collagen Mutations Database.

  16. A novel splicing mutation in COL1A1 gene caused type I osteogenesis imperfecta in a Chinese family.

    Science.gov (United States)

    Peng, Hao; Zhang, Yuhui; Long, Zhigao; Zhao, Ding; Guo, Zhenxin; Xue, Jinjie; Xie, Zhiguo; Xiong, Zhimin; Xu, Xiaojuan; Su, Wei; Wang, Bing; Xia, Kun; Hu, Zhengmao

    2012-07-10

    Osteogenesis imperfect (OI) is a heritable connective tissue disorder with bone fragility as a cardinal manifestation, accompanied by short stature, dentinogenesis imperfecta, hyperlaxity of ligaments and skin, blue sclerae and hearing loss. Dominant form of OI is caused by mutations in the type I procollagen genes, COL1A1/A2. Here we identified a novel splicing mutation c.3207+1G>A (GenBank ID: JQ236861) in the COL1A1 gene that caused type I OI in a Chinese family. RNA splicing analysis proved that this mutation created a new splicing site at c.3200, and then led to frameshift. This result further enriched the mutation spectrum of type I procollagen genes. PMID:22565191

  17. Rib cage deformities alter respiratory muscle action and chest wall function in patients with severe osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Antonella LoMauro

    Full Text Available BACKGROUND: Osteogenesis imperfecta (OI is an inherited connective tissue disorder characterized by bone fragility, multiple fractures and significant chest wall deformities. Cardiopulmonary insufficiency is the leading cause of death in these patients. METHODS: Seven patients with severe OI type III, 15 with moderate OI type IV and 26 healthy subjects were studied. In addition to standard spirometry, rib cage geometry, breathing pattern and regional chest wall volume changes at rest in seated and supine position were assessed by opto-electronic plethysmography to investigate if structural modifications of the rib cage in OI have consequences on ventilatory pattern. One-way or two-way analysis of variance was performed to compare the results between the three groups and the two postures. RESULTS: Both OI type III and IV patients showed reduced FVC and FEV(1 compared to predicted values, on condition that updated reference equations are considered. In both positions, ventilation was lower in OI patients than control because of lower tidal volume (p<0.01. In contrast to OI type IV patients, whose chest wall geometry and function was normal, OI type III patients were characterized by reduced (p<0.01 angle at the sternum (pectus carinatum, paradoxical inspiratory inward motion of the pulmonary rib cage, significant thoraco-abdominal asynchronies and rib cage distortions in supine position (p<0.001. CONCLUSIONS: In conclusion, the restrictive respiratory pattern of Osteogenesis Imperfecta is closely related to the severity of the disease and to the sternal deformities. Pectus carinatum characterizes OI type III patients and alters respiratory muscles coordination, leading to chest wall and rib cage distortions and an inefficient ventilator pattern. OI type IV is characterized by lower alterations in the respiratory function. These findings suggest that functional assessment and treatment of OI should be differentiated in these two forms of the

  18. A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

    Science.gov (United States)

    Patel, R M; Nagamani, S C S; Cuthbertson, D; Campeau, P M; Krischer, J P; Shapiro, J R; Steiner, R D; Smith, P A; Bober, M B; Byers, P H; Pepin, M; Durigova, M; Glorieux, F H; Rauch, F; Lee, B H; Hart, T; Sutton, V R

    2015-02-01

    Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing.

  19. Clinical Aspects, Imaging Features, and Considerations on Bisphosphonate-Related Osteonecrosis Risk in a Pediatric Patient with Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Fábio Wildson Gurgel Costa

    2014-01-01

    Full Text Available Osteogenesis imperfecta (OI is a rare hereditary condition caused by changes in collagen metabolism. It is classified into four types according to clinical, genetic, and radiological criteria. Clinically, bone fragility, short stature, blue sclerae, and locomotion difficulties may be observed in this disease. OI is often associated to severe dental problems, such as dentinogenesis imperfecta (DI and malocclusions. Radiographically, affected teeth may have crowns with bulbous appearance, accentuated constriction in the cementoenamel junction, narrowed roots, large root canals due to defective dentin formation, and taurodontism (enlarged pulp chambers. There is no definitive cure, but bisphosphonate therapy is reported to improve bone quality; however, there is a potential risk of bisphosphonate-related osteonecrosis of the jaw. In this study we report a case of OI in a male pediatric patient with no family history of OI who was receiving ongoing treatment with intravenous perfusion of bisphosphonate and who required dental surgery. In addition, we discussed the clinical and imaging findings and briefly reviewed the literature.

  20. Osteogenesis imperfecta Type VI with severe bony deformities caused by novel compound heterozygous mutations in SERPINF1.

    Science.gov (United States)

    Cho, Sung Yoon; Ki, Chang-Seok; Sohn, Young Bae; Kim, Su Jin; Maeng, Se Hyun; Jin, Dong-Kyu

    2013-07-01

    Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by bone fragility, frequent fractures, and low bone mass. Dominantly inherited COL1A1 or COL1A2 mutations appear to be causative in the majority of OI types, but rare recessively inherited genes have also been reported. Recently, SERPINF1 has been reported as another causative gene in OI type VI. To date, only eight SERPINF1 mutations have been reported and all are homozygous. Our patient showed no abnormalities at birth, frequent fractures, osteopenia, and poor response on pamidronate therapy. At the time of her most recent evaluation, she was 8 yr old, and could not walk independently due to frequent lower-extremity fractures, resulting in severe deformity. No clinical signs were seen of hearing impairment, blue sclera, or dentinogenesis imperfecta. In this study, we describe the clinical and radiological findings of one Korean patient with novel compound heterozygous mutations (c.77dupC and c.421dupC) of SERPINF1.

  1. OI Issues: Type I - Understanding the Mildest Form of Osteogenesis Imperfecta

    Science.gov (United States)

    ... counseling can address both types of problems. A nutritionist can design a diet that is rich in ... with Type I OI recommend developing an effective personal support network. Resources For more information about osteogenesis ...

  2. Osteogenesis Imperfecta with Celiac Disease and Type II Diabetes Mellitus Associated: Improvement with a Gluten-Free Diet

    Directory of Open Access Journals (Sweden)

    Luis Rodrigo

    2012-01-01

    Full Text Available Osteogenesis imperfecta (OI is a genetic disease, with a connective tissue alteration, consisting in the presence of multiple spontaneous fractures or after minimal traumatism. Its association with other metabolic processes is rarely described. We present the clinical case of a female adult patient of 43 years. From her infancy, she has had multiple fractures, needing several surgical interventions, and she was diagnosed of OI type 2 at adolescence age. Due mainly to difficulties in walking remaining in wheel-chair in the last three years, she was overweight with morbid obesity (BMI=45.4 and had a type-II DM associated. She suffered from recurrent abdominal pain and chronic diarrhea and was diagnosed of celiac disease (CD with increased intraepithelial duodenal infiltration, being classified as lymphocytic enteritis, Marsh I type. She was put on a gluten-free diet (GFD, having lost 6 kg of weight after 6 months, with a good control of DM-II and presenting a significant clinical improvement. It is rewarding to search the presence of two coincidental metabolic diseases associated to OI, specially CD, because of the dramatic clinical benefit in the general found after putting on a GFD.

  3. Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    Douglas J DiGirolamo; Vandana Singhal; Xiaoli Chang; Se-Jin Lee; Emily L Germain-Lee

    2015-01-01

    Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.

  4. Osteogenesis imperfecta Type I caused by a novel mutation in the start codon of the COL1A1 gene in a Korean family.

    Science.gov (United States)

    Cho, Sung Yoon; Lee, Ji-Ho; Ki, Chang-Seok; Chang, Mi Sun; Jin, Dong-Kyu; Han, Heon-Seok

    2015-01-01

    Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by susceptibility to bone fractures ranging in severity from perinatal death to a subtle increase in fracture frequency. We report the case of a patient who appeared healthy at birth and did not experience any fractures until 12 months of age. We observed blue sclera, frequent fractures without commensurate trauma, nearly normal stature, the absence of dentinogenesis imperfecta, no bony deformity, and no limitation of mobility in the patient--all characteristics suggestive of OI Type I. The patient's mother also had blue sclera and a history of frequent fracture episodes until the age of 15 years. A novel COL1A1 missense mutation (c.2T>G) disrupting the start codon of the gene (ATG to AGG (Met1Arg)) was found in the patient and his mother.

  5. Bone geometry, density and microarchitecture in the distal radius and tibia in adults with osteogenesis imperfecta type-1 assessed by HR-pQCT

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Hansen, Stinus;

    2012-01-01

    Osteogenesis Imperfecta (OI) is a hereditary disorder characterized by decreased biosynthesis or impaired morphology of collagen type-1 that leads to decreased bone mass and increased bone fragility. We hypothesized that patients with OI have altered bone microstructure and bone geometry. In this...... treated with bisphosphonates. HR-pQCT at the distal radius and distal tibia and dual-energy X-ray absorptiomentry of total hip, femoral neck, trochanteric region and the lumbar spine (L1-L4) were performed. The patients were shorter than the controls (159¿±¿10¿cm vs. 170¿±¿9¿cm, p¿...

  6. Identification and molecular characterization of two novel mutations in COL1A2 in two Chinese families with osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    Zhenping Xu; Yulei Li; Xiangyang Zhang; Fanming Zeng; Mingxiong Yuan; Mugen Liu; Qing Kenneth Wang; Jing Yu Liu

    2011-01-01

    Osteogenesis imperfecta (OI, also known as brittle bone disease) is caused mostly by mutations in two type Ⅰ collagen genes, COL1A1 and COL1A2 encoding the pro-α1 (Ⅰ) and pro-α2 (Ⅰ) chains of type Ⅰ collagen, respectively. Two Chinese families with autosomal dominant OI were identified and characterized. Linkage analysis revealed linkage of both families to COL1A2 on chromosome 7q21.3-q22.1. Mutational analysis was carried out using direct DNA sequence analysis. Two novel missense mutations, c.3350A>G and c.3305G>C, were identified in exon 49 of COL1A2 in the two families, respectively. The c.3305G>C mutation resulted in substitution of a glycine residue (G) by an alanine residue (A) at codon 1102 (p.G1102A), which was found to be mutated into serine (S), argine (R), aspartic acid (D), or valine (V) in other families. The c.3350A>G variant may be a de novo mutation resulting in p.Y1117C. Both mutations co-segregated with OI in respective families, and were not found in 100 normal controls. The G1102 and Y1117 residues were evolutionarily highly conserved from zebrafish to humans. Mutational analysis did not identify any mutation in the COX-2 gene (a modifier gene of OI). This study identifies two novel mutations p.G1102A and p.Y1117C that cause OI, significantly expands the spectrum of COL1A2 mutations causing OI, and has a significant implication in prenatal diagnosis of OI.

  7. Molecular Consequences of the SERPINH1/HSP47 Mutation in the Dachshund Natural Model of Osteogenesis Imperfecta*

    Science.gov (United States)

    Lindert, Uschi; Weis, Mary Ann; Rai, Jyoti; Seeliger, Frank; Hausser, Ingrid; Leeb, Tosso; Eyre, David; Rohrbach, Marianne; Giunta, Cecilia

    2015-01-01

    Osteogenesis imperfecta (OI) is a heritable connective tissue disease characterized by bone fragility and increased risk of fractures. Up to now, mutations in at least 18 genes have been associated with dominant and recessive forms of OI that affect the production or post-translational processing of procollagen or alter bone homeostasis. Among those, SERPINH1 encoding heat shock protein 47 (HSP47), a chaperone exclusive for collagen folding in the ER, was identified to cause a severe form of OI in dachshunds (L326P) as well as in humans (one single case with a L78P mutation). To elucidate the disease mechanism underlying OI in the dog model, we applied a range of biochemical assays to mutant and control skin fibroblasts as well as on bone samples. These experiments revealed that type I collagen synthesized by mutant cells had decreased electrophoretic mobility. Procollagen was retained intracellularly with concomitant dilation of ER cisternae and activation of the ER stress response markers GRP78 and phospho-eIF2α, thus suggesting a defect in procollagen processing. In line with the migration shift detected on SDS-PAGE of cell culture collagen, extracts of bone collagen from the OI dog showed a similar mobility shift, and on tandem mass spectrometry, the chains were post-translationally overmodified. The bone collagen had a higher content of pyridinoline than control dog bone. We conclude that the SERPINH1 mutation in this naturally occurring model of OI impairs how HSP47 acts as a chaperone in the ER. This results in abnormal post-translational modification and cross-linking of the bone collagen. PMID:26004778

  8. Recurrent Proximal Femur Fractures in a Teenager With Osteogenesis Imperfecta on Continuous Bisphosphonate Therapy: Are We Overtreating?

    Science.gov (United States)

    Vasanwala, Rashida F; Sanghrajka, Anish; Bishop, Nicholas J; Högler, Wolfgang

    2016-07-01

    Long-term bisphosphonate (BP) therapy in adults with osteoporosis is associated with atypical femoral fractures, caused by increased material bone density and prolonged suppression of bone remodeling which may reduce fracture toughness. In children with osteogenesis imperfecta (OI), long-term intravenous BP therapy improves bone structure and mass without further increasing the already hypermineralized bone matrix, and is generally regarded as safe. Here we report a teenage girl with OI type IV, who was started on cyclical intravenous pamidronate therapy at age 6 years because of recurrent fractures. Transiliac bone biopsy revealed classical structural features of OI but unusually low bone resorption surfaces. She made substantial improvements in functional ability, bone mass, and fracture rate. However, after 5 years of pamidronate therapy she started to develop recurrent, bilateral, nontraumatic, and proximal femur fractures, which satisfied the case definition for atypical femur fractures. Some fractures were preceded by periosteal reactions and prodromal pain. Pamidronate was discontinued after 7 years of therapy, following which she sustained two further nontraumatic femur fractures, and continued to show delayed tibial osteotomy healing. Despite rodding surgery, and very much in contrast to her affected, untreated, and normally mobile mother, she remains wheelchair-dependent. The case of this girl raises questions about the long-term safety of BP therapy in some children, in particular about the risk of oversuppressed bone remodeling with the potential for microcrack accumulation, delayed healing, and increased stiffness. The principal concern is whether there is point at which benefit from BP therapy could turn into harm, where fracture risk increases again. This case should stimulate debate whether current adult atypical femoral fracture guidance should apply to children, and whether low-frequency, low-dose cyclical, intermittent, or oral treatment

  9. Results of a bone splint technique for the treatment of lower limb deformities in children with type I osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Dasheng Lin

    2013-01-01

    Full Text Available Background: Children with osteogenesis imperfecta (OI can suffer from frequent fractures and limb deformities, resulting in impaired ambulation. Osteopenia and thin cortices complicate orthopedic treatment in this group. This study evaluates the clinical results of a bone splint technique for the treatment of lower limb deformities in children with type I OI. The technique consists of internal plating combined with cortical strut allograft fixation. Materials and Methods: We prospectively followed nine children (five boys, four girls with lower limb deformities due to type I OI, who had been treated with the bone splint technique (11 femurs, four tibias between 2003 and 2006. The fracture healing time, deformity improvement, ambulation ability and complications were recorded to evaluate treatment effects. Results: At the time of surgery the average age in our study was 7.7 years (range 5-12 years. The average length of followup was 69 months (range 60-84 months. All patients had good fracture healing with an average healing time of 14 weeks (range 12-16 weeks and none experienced further fractures, deformity, or nonunion. The fixation remained stable throughout the procedure in all cases, with no evidence of loosening or breakage of screws and the deformity and mobility significantly improved after surgery. Of the two children confined to bed before surgery, one was able to walk on crutches and the other needed a wheelchair. The other seven patients could walk without walking aids or support like crutches. Conclusions: These findings suggest that the bone splint technique provides good mechanical support and increases the bone mass. It is an effective treatment for children with OI and lower limb deformities.

  10. The phenotypic features of osteogenesis imperfecta resulting from a mutation of the carboxyl-terminal pro alpha 1(I) propeptide that impairs the assembly of type I procollagen and formation of the extracellular matrix

    NARCIS (Netherlands)

    Cole, WG; Chow, CW; Bateman, JF; Sillence, DO

    1996-01-01

    The features of a baby with lethal perinatal osteogenesis imperfecta (OI-II), resulting from the substitution of tryptophan 94 by cysteine in the carboxyl-terminal propeptide of pro alpha 1(I) chains of type I procollagen, were studied. The limbs and torso were of normal length, shape, and proportio

  11. Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

    Science.gov (United States)

    Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2016-09-01

    Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1. PMID:27297606

  12. Determination of a new collagen type I alpha 2 gene point mutation which causes a Gly640 Cys substitution in osteogenesis imperfecta and prenatal diagnosis by DNA hybridisation.

    Science.gov (United States)

    Gomez-Lira, M; Sangalli, A; Pignatti, P F; Digilio, M C; Giannotti, A; Carnevale, E; Mottes, M

    1994-01-01

    The molecular defect responsible for a sporadic case of extremely severe (type II/III) osteogenesis imperfecta was investigated. The mutation site was localised in the collagen type I pro alpha 2 mRNA molecules produced by the proband's skin fibroblasts by chemical cleavage of mismatch in heteroduplex nucleic acids. Reverse transcription-polymerase chain reaction DNA amplification, followed by cloning and sequencing, showed heterozygosity for a G to T transversion in the first nucleotide of exon 37 of the COL1A2 gene, which led to a cysteine for glycine substitution at position 640 of the triple helical domain. This newly characterised mutation is localised in a domain which contains several milder mutations, confirming that glycine substitutions within the alpha 2(I) chain do not follow a linear gradient pattern for genotype to phenotype correlations. In a subsequent pregnancy, absence of the G2327T mutation in the fetus was shown by allele specific oligonucleotide hybridisation to the trophoblast derived fibroblast mRNA after reverse transcription and in vitro amplification. (The nucleotide number assigned to the mutant base was inferred from the numbering system devised by the Osteogenesis Imperfecta Analysis Consortium (The OIAC Newsletter, 1 April 1994).) Images PMID:7891382

  13. Tratamento cirúrgico das deformidades e fraturas em membros inferiores na osteogênese imperfeita Surgical treatment of deformities and fractures on lower limbs with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Marcelo de Toledo Piza Watzl

    2009-01-01

    Full Text Available OBJETIVO: Fazer uma revisão dos pacientes portadores de Osteogênese Imperfeita avaliando o tratamento cirúrgico das fraturas e deformidades nos membros inferiores para determinar a eficiência da técnica utilizando as hastes fixas (não-extensíveis. CASUÍSTICA E MÉTODO: Foram revisados os prontuários, radiografias pré-operatórias e pós-operatórias de todos os pacientes portadores de Osteogênese Imperfeita que foram tratados no Alfred I duPont Institute (EUA entre 1965 e 1999. RESULTADOS: Quatorze pacientes (cinco meninos e nove meninas foram submetidos às hastes fixas nos membros inferiores com um total de 37 procedimentos realizados. CONCLUSÃO: O procedimento de fixação intramedular com hastes não extensíveis mostrou ser um método de baixa morbidade, capaz de manter e até mesmo de melhorar o status de deambulador destes pacientes.OBJECTIVE: To provide a review of patients with Osteogenesis Imperfecta by analyzing the deformities, fractures and results of surgical treatment on lower limbs in order to determine the efficiency of the use of non-elongating rods (non extensible. MATERIALS AND METHOD: Medical records, preoperative and postoperative X-ray images of all the patients who had imperfect osteogenesis and treated at the Alfred I duPont Institute (USA between 1965 and 1999 have been reviewed. RESULTS: Fourteen patients (five boys and nine girls were submitted to the non-elongating rods on their lower limbs, totaling 37 procedures. CONCLUSION: The procedure of intramedullary fixation with non-elongating rods to treat fractures and deformities on lower limb in Osteogenesis Imperfecta was proven to be a low morbidity method without interfering with the ambulatory status of these patients.

  14. Dentinogenesis imperfecta: a case report.

    Science.gov (United States)

    Subramaniam, P; Mathew, S; Sugnani, S N

    2008-06-01

    Dentinogenesis imperfecta is an autosomal dominant disorder of tooth development characterized by the presence of opalescent dentin, resulting in a dusky blue to brownish discoloration of the teeth. This condition is genetically and clinically heterogeneous; it may affect only the teeth or it may be associated with the osteogenesis imperfecta. Dentinogenesis imperfecta has been subdivided into three types: type I is associated with osteogenesis imperfecta; in type II there is no associated osteogenesis imperfecta; and when the condition is associated with the Brandywine triracial isolate and large pulp chambers it is classified as type III. This report describes a 16-year-old female patient who showed the characteristic dental features of dentinogenesis imperfecta type II. The etiology and prevalence of the disorder, and a comprehensive treatment plan, will be briefly reviewed.

  15. Dentinogenesis imperfecta: A case report

    Directory of Open Access Journals (Sweden)

    Subramaniam P

    2008-06-01

    Full Text Available Dentinogenesis imperfecta is an autosomal dominant disorder of tooth development characterized by the presence of opalescent dentin, resulting in a dusky blue to brownish discoloration of the teeth. This condition is genetically and clinically heterogeneous; it may affect only the teeth or it may be associated with the osteogenesis imperfecta. Dentinogenesis imperfecta has been subdivided into three types: type I is associated with osteogenesis imperfecta; in type II there is no associated osteogenesis imperfecta; and when the condition is associated with the Brandywine triracial isolate and large pulp chambers it is classified as type III. This report describes a 16-year-old female patient who showed the characteristic dental features of dentinogenesis imperfecta type II. The etiology and prevalence of the disorder, and a comprehensive treatment plan, will be briefly reviewed.

  16. Dental implications of osteogenesis imperfecta: treatment with IV bisphosphonate: report of a case.

    Science.gov (United States)

    Milano, Michael; Wright, Timothy; Loechner, Karen J

    2011-01-01

    Osteogenesis imperfect (OI) is a group of genetically diverse connective tissue disorders. Bisphosphonates therapy to manage bone fragility, a now common medical therapy for OI, can increase the risk of bisphosphonate-associated osteonecrosis of the jaws. In this report, a 6 ½ year child, who was receiving bisphosphonate therapy for OI, underwent full mouth dental rehabilitation in the operating room while under general anesthesia. The child had numerous teeth restored and multiple primary molar extractions. The patient, who received prophylactic antibiotics intraoperatively, demonstrated no clinical signs of bisphosphonate-associated osteonecrosis when seen at follow-up. Although bisphosphonate osteonecrosis is a possible sequel in children who receive multiple extractions, no clinical signs were manifested in our patient, who required multiple primary tooth extractions along with restorative treatment under general anesthesia. While no dental guidelines have been developed to manage OI children having been treated with bisphosphonates, consent for extractions should include the risk of bone necrosis and careful post-operative observation to monitor wound healing. PMID:21903004

  17. RANKL inhibition improves bone properties in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Bargman, Renee; Huang, Alice; Boskey, Adele L; Raggio, Cathleen; Pleshko, Nancy

    2010-04-01

    Recently, a new class of agents targeting the receptor activator of nuclear factor-kappaB ligand (RANKL) pathway has been developed for the treatment of osteoporosis and other bone diseases. In the current study, inhibition of the RANKL pathway was evaluated to assess effects on "bone quality" and fracture incidence in an animal model of osteogenesis imperfect (OI), the oim/oim mouse. Juvenile oim/oim ( approximately 6 weeks old) and wildtype (+/+) mice were treated with either a RANKL inhibitor (RANK-Fc) or saline. After treatment, bone density increased significantly in the femurs of both genotypes. Femoral length decreased with RANK-Fc in +/+ mice. Geometric measurements at mid-diaphysis in the oim/oim groups showed increases in the ML periosteal and endosteal diameters and AP cortical thickness in the treated groups. Within +/+ groups, ML cortical thickness and ML femoral periosteal diameter were significantly increased with RANK-Fc. Biomechanical testing revealed increased stiffness in oim/oim and +/+ mice. Total strain was increased with treatment in the +/+ mice. Histologically, RANKL inhibition resulted in retained growth plate cartilage in both genotypes. The average number of fractures sustained by RANK-Fc-treated oim/oim mice was not significantly decreased compared to saline treated oim/oim mice. This preclinical study demonstrated that RANKL inhibition at the current dose improved density and some geometric and biomechanical properties of oim/oim bone, but it did not decrease fracture incidence. Further studies that address commencement of therapy at earlier time points are needed to determine whether this mode of therapy will be clinically useful in OI. PMID:20053133

  18. AB019. Osteogenesis imperfecta 2015: new genes, new treatments—an Asia pacific perspective

    Science.gov (United States)

    Sillence, David

    2015-01-01

    For 40 years the pathogenesis of the group of brittle bone disorders collectively named osteogenesis imperfect (OI) has been ascribed to mutations in type I collagen. Recent discoveries in matrix biology have transformed our perspectives on the role of mutations in the α1- and α2-chains of type I collagen (COLIA1, COLIA2), their post-translational modifications, trafficking and matrix interactions. Furthermore progress in gene discovery has identified 22 genes including the 2 COLI genes, in which mutations result in at least one OI phenotype. The International Bone Dysplasia Committee has grouped the syndromes arising from mutations in these genes into five OI phenotypes. All 3 modes of inheritance, Autosomal Dominant (4 genes) and Recessive (16 genes), X-linked (2 genes) have been discovered. The gene products of the recessive genes have a variety of functions. Mutations in LEPRE1, CRTAP and PIPB regulate prolyl-3-hydroxylation. A recent study in Crtap−/− mice showed upregulation of TGF-β target genes and reduced binding of type 1 collagen to the proteoglycan decorin. A similar pattern of TGFB dysregulation was observed in the tissues of heterozygous Col1a2tm1.1 Mcbr mice. Mutations in FKBP10, SERPINF1 (HSP10), SERPINH1 affect polypeptide trafficking but have other matrix functions. Mutations in PLOD2 and FKBP10 both have extra-skeletal effects on matrices resulting in joint contractures. Mineralisation and osteoclast function are affected by mutations in LRP5, SP7, TMEM38B, WNT1, IFITM5 and CREB3L1 (OASIS), SPARC as do hemizygous mutations in the X-linked gene PLS3. A role for the unfolded protein response (UPR) is observed in the pathogenesis of OI resulting from mutation in CREB3L1. There is some evidence that the frequency of the varying types of OI may vary in and between populations in Asia and the Pacific. OI with Congenital Joint contractures for example is of high frequency in Samoa and Tonga and may well be common in a source community in Asia

  19. Ⅰ型成骨不全一家系的分子诊断%Molecular diagnosis of a Chinese pedigree with osteogenesis imperfecta type Ⅰ

    Institute of Scientific and Technical Information of China (English)

    柯龙凤; 郑林文; 谢海花; 严爱贞; 朱忠勇; 兰风华

    2009-01-01

    Objective To perform molecular diagnosis for a Chinese pedigree with osteogenesis imperfecta type Ⅰ.Methods Thirty pairs of primers were designed tO amplify all the 52 exons,exon boundaries and promoter region of the COL1A1 gene from genomic DNA of peripheral blood cells of the family members.The PCR products were purified and directly sequenced.To check the mutation in normal controls.the genomic DNA from peripheral blood cells of the index patient,his mother and 60 normal controls were analyzed by amplification refractory mutation system.ResultsA missense mutation of GAT >CAT was identified at codon 1441 of the COL1A1 gene from the family,which resulted in the replacement of aspartic acid by histidine(D1441H).This mutation was not found in a group of 60 normal controls.Conclusion The method for molecular diagnosis of osteogenesis imperfecta was established and a novel COL1A1 gene mutation,D1441H,was identified in the Chinese pedigree with osteogenesis imperfecta type Ⅰ.%目的 对Ⅰ型成骨不全(osteogenesis imperfecta,OI)1个家系进行分子诊断.方法 从先证者的基因组DNA人手,自行设计30对引物,扩增产物涵盖全部COL1A1基因52个外显子及启动子区域,并以相应引物对PCR产物进行直接测序.针对突变位点,设计扩增阻滞突变系统(amplification refractory mutation system,ARMS)引物,在60名无关对照中进行突变筛查.结果 在先证者的其中1条COL1A1等位基因上存在突变,即COL1A1基因第1441位(位于第52外显子,P30)发生了GAT→CAT改变.使原来编码的天冬氨酸被组氨酸取代(D1441H);其母亲的其中1条COL1A1等位基因上也存在相同突变,而正常对照相应的COL1A1基因序列与GenBank参考序列相同.ARMS分析显示,在60个无关对照中均未检测到D1441H突变.查阅国内外相关文献及COL1A1基因突变数据库,未发现有关COL1A1基因D1441H突变的报道.结论 建立了基于COL1A1基因突变分析的成骨不全分子诊断方法 ,

  20. Learning about Osteogenesis Imperfecta

    Science.gov (United States)

    ... to create a larger molecule called type I collagen. This type of collagen is the most common protein in bone, skin ... taken from a small skin biopsy. Changes in type I collagen are an indication of OI. DNA sequencing of ...

  1. Identification of a novel COL1A1 frameshift mutation, c.700delG, in a Chinese osteogenesis imperfecta family.

    Science.gov (United States)

    Wang, Xiran; Pei, Yu; Dou, Jingtao; Lu, Juming; Li, Jian; Lv, Zhaohui

    2015-03-01

    Osteogenesis imperfecta (OI) is a family of genetic disorders associated with bone loss and fragility. Mutations associated with OI have been found in genes encoding the type I collagen chains. People with OI type I often produce insufficient α1-chain type I collagen because of frameshift, nonsense, or splice site mutations in COL1A1 or COL1A2. This report is of a Chinese daughter and mother who had both experienced two bone fractures. Because skeletal fragility is predominantly inherited, we focused on identifying mutations in COL1A1 and COL1A2 genes. A novel mutation in COL1A1, c.700delG, was detected by genomic DNA sequencing in the mother and daughter, but not in their relatives. The identification of this mutation led to the conclusion that they were affected by mild OI type I. Open reading frame analysis indicated that this frameshift mutation would truncate α1-chain type I collagen at residue p263 (p.E234KfsX264), while the wild-type protein would contain 1,464 residues. The clinical data were consistent with the patients' diagnosis of mild OI type I caused by haploinsufficiency of α1-chain type I collagen. Combined with previous reports, identification of the novel mutation COL1A1-c.700delG in these patients suggests that additional genetic and environmental factors may influence the severity of OI.

  2. Local amino acid sequence patterns dominate the heterogeneous phenotype for the collagen connective tissue disease Osteogenesis Imperfecta resulting from Gly mutations.

    Science.gov (United States)

    Xiao, Jianxi; Yang, Zhangfu; Sun, Xiuxia; Addabbo, Rayna; Baum, Jean

    2015-10-01

    Osteogenesis Imperfecta (OI), a hereditary connective tissue disease in collagen that arises from a single Gly → X mutation in the collagen chain, varies widely in phenotype from perinatal lethal to mild. It is unclear why there is such a large variation in the severity of the disease considering the repeating (Gly-X-Y)n sequence and the uniform rod-like structure of collagen. We systematically evaluate the effect of local (Gly-X-Y)n sequence around the mutation site on OI phenotype using integrated bio-statistical approaches, including odds ratio analysis and decision tree modeling. We show that different Gly → X mutations have different local sequence patterns that are correlated with lethal and nonlethal phenotypes providing a mechanism for understanding the sensitivity of local context in defining lethal and non-lethal OI. A number of important trends about which factors are related to OI phenotypes are revealed by the bio-statistical analyses; most striking is the complementary relationship between the placement of Pro residues and small residues and their correlation to OI phenotype. When Pro is present or small flexible residues are absent nearby a mutation site, the OI case tends to be lethal; when Pro is present or small flexible residues are absent further away from the mutation site, the OI case tends to be nonlethal. The analysis also reveals the dominant role of local sequence around mutation sites in the Major Ligand Binding Regions that are primarily responsible for collagen binding to its receptors and shows that non-lethal mutations are highly predicted by local sequence considerations alone whereas lethal mutations are not as easily predicted and may be a result of more complex interactions. Understanding the sequence determinants of OI mutations will enhance genetic counseling and help establish which steps in the collagen hierarchy to target for drug therapy.

  3. Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta.

    Directory of Open Access Journals (Sweden)

    Wayne A Cabral

    2016-07-01

    Full Text Available Recessive osteogenesis imperfecta (OI is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. The molecular mechanisms by which TMEM38B mutations cause OI are unknown. We identified 3 probands with recessive defects in TMEM38B. TRIC-B protein is undetectable in proband fibroblasts and osteoblasts, although reduced TMEM38B transcripts are present. TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability. Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery. The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps. Collagen helical lysine hydroxylation is reduced, while telopeptide hydroxylation is increased, despite increased LH1 and decreased Ca2+-dependent FKBP65, respectively. Although PDI levels are maintained, procollagen chain assembly is delayed in proband cells. The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50-70% reduction in secreted collagen. Lower-stability forms of collagen that elude proteasomal degradation are not incorporated into extracellular matrix, which contains only normal stability collagen, resulting in matrix insufficiency. These data support a role for TRIC-B in intracellular Ca2+ homeostasis, and demonstrate that absence of TMEM38B causes OI by dysregulation of calcium flux kinetics in the ER, impacting multiple collagen-specific chaperones and modifying enzymes.

  4. Corrective osteotomy for the treatment of femoral deformity in children with osteogenesis imperfecta%成骨不全股骨畸形的截骨矫形

    Institute of Scientific and Technical Information of China (English)

    张鹏; 王延宙; 张敏刚; 王恒冰; 王继孟

    2010-01-01

    目的 探讨多段截骨矫形治疗成骨不全儿童股骨畸形的手术特点和临床效果.方法 2004年1月至2007年1月,采用多段截骨矫形+Rush钉内固定,治疗成骨不全股骨畸形10例(共14根股骨).其中男7例,女3例,年龄5~16岁,平均年龄10.3岁.术后进行临床评价(活动方式、股骨长度和感染)和放射学评价(Rush钉的位置、移位、弯曲、断裂和再骨折).结果 随访3~5年,平均3.5年,所有病例均骨性愈合,愈合时间6~9周,平均7周;首次手术的平均年龄为6.1岁,4例需要二次手术更换Rush钉;首次与第二次手术的时间间隔为1.5~4年,平均2.7年.所有病例未发生骨折、血管神经损伤、感染、骨不连等并发症;股骨畸形和下肢功能获得明显改善(P<0.01).其中1例未及时更换Rush钉.其远端自骨干穿出,局部成角畸形,给予截骨矫形、更换Rush钉后治愈.结论 术前个性化设计,采取多段截骨矫形治疗成骨不全儿童的股骨畸形,可以加速骨愈合,减少再骨折;最大可能的矫正畸形,改善下肢功能,提高生活质量.%Objective To evaluate the surgical strategies and outcomes of multiple corrective osteotomy for the treatment of femoral deformity in children with osteogenesis imperfecta.Methods Between 2004 and 2007,14 femora of 10 patients with osteogenesis imperfect,who underwent recurrent fractures and/or deformities in the femora at this center,were recruited in this study.They included 7 males and 3 females,aged from 5 to 16 years old(mean age,10.3 years old).The femoral deformities were corrected by multiple corrective osteotomy and Rush pins.After surgery,the clinical conditions of these patients regarding mobility status,growth and limb-length,and infection were followed up.Radiological images were taken to monitor pin placement,migration,bending,breakage of pins,and refracture of femora.Results The average duration of follow-up was 3.5 years(ranged from 3 to 5 years).Union was

  5. Intubação nasotraqueal guiada por rinoscópio em criança de um ano de idade portadora de Osteogenesis imperfecta: relato de caso Intubación nasotraqueal guiada por rinoscopio en niño de un año de edad portador de Osteogenesis imperfecta: relato de caso Rhinoscope-guided nasotracheal intubation in a one-year old child with Osteogenesis imperfecta: case report

    Directory of Open Access Journals (Sweden)

    Eduardo Toshiyuki Moro

    2009-10-01

    de esa enfermedad asociada a la hidrocefalia, y sometido a la anestesia venosa total e intubación nasotraqueal, guiada por rinoscopio para la realización de la derivación ventrículo-peritoneal. RELATO DEL CASO: Paciente del sexo masculino, un año y tres meses de edad, con diagnósticos de OI (tipo III e hidrocefalia sometido a la derivación ventrículo-peritoneal. Después de la administración de midazolam (1 mg.kg-1 por vía oral, 30 minutos antes del procedimiento, el niño fue monitorizado, con posterior venoclisis con catéter 24G. Después de la oxigenación, se procedió a la inducción anestésica con remifentanil, propofol y cisatracurio. La intubación nasotraqueal fue guiada por rinolaringoscopio (Olimpus® ENF P3 y cánula de 4,5 mm con balón e insertada sin intercurrencias. La anestesia se mantuvo con infusión de remifentanil y propofol. La operación duró 120 minutos sin intercurrencias. CONCLUSIONES: El presente relato describió una alternativa de acceso a la vía aérea en niños sometidos a la anestesia general y que por algún motivo no pueden ser ventilados a través de la máscara laríngea. El rinolaringoscopio, por presentar un diámetro reducido, permite la inserción de cánulas traqueales que no podrían ser utilizadas con el uso del fibroscopio convencional.BACKGROUND AND OBJECTIVES: Osteogenesis imperfecta (OI is a rare, autosomal dominant disease. Anesthesia for patients with OI has several challenges; among them, management of the airways and the choice of anesthetic technique should be mentioned. The objective of this report was to describe the case of a child with this disorder associated with hydrocephalus who underwent total intravenous anesthesia and rhinoscope-guided nasotracheal intubation for a ventriculoperitoneal shunt. CASE REPORT: This is a 15-month old male with OI (type III and hydrocephalus who underwent placement of a ventriculoperitoneal shunt. After the oral administration of midazolam (1 mg.kg-1 30 minutes

  6. 一例成骨不全Ⅱ型高危胎儿的产前基因诊断%Prenatal gene diagnosis of a high-risk fetus with osteogenesis imperfecta type Ⅱ

    Institute of Scientific and Technical Information of China (English)

    艾阳; 唐佳; 方群; 吴晓昀; 郭奕斌

    2011-01-01

    目的 对广东一疑似致死性侏儒症或成骨不全Ⅱ型的高危胎儿实施产前基因诊断,以阐明胎儿骨发育异常的真实病因,及时预防患胎出生.方法 对经超声检查初诊为致死性侏儒症或成骨不全、已孕25周的高危胎儿,在抽取脐血制备DNA模板后,采用PCR-DNA直接测序法,分别对胎儿的FGFR3基因和COL1A1基因进行突变检测,然后对所发现的突变进行分析和鉴定.结果 FGFR3基因未发现病理性突变,而COL1A1基因发现一典型的杂合错义突变(c.3065 G>T,PG1022V),经查HGMD数据库证实为成骨不全Ⅱ型的致病性突变.结论 (1)此高危胎儿为成骨不全Ⅱ型患胎,应及时终止妊娠(胎儿已经引产,经复查证实与产前基因诊断结果完全一致).(2)在超声初诊基础上,采用产前基因诊断可快速、有效对高危胎儿做出确诊,为出生缺陷的预防提供技术保障.%Objective To clarify the real pathogeny of the dysostoses of fetuses ,the prenatal gene diagnosis of a Guangdong high-risk fetus suspected with osteogenesis imperfecta type II or thanatophoric dwarfism was carried out, which stopped the birth of the suffering fetuses. Methods The high-risk fetus of 25 weeks was preliminarily diagnosed with thanatophoric dwarfism or osteogenesis imperfecta by ultrasonic test. The cord blood was extracted to make preparation for DNA template ,PCR-DNA sequencing was used to detect the mutation of FGFR3 gene and COL1A1 gene,then the mutations were analyzed and identified. Results There was no pathological mutation on the FGFR3 gene. There was a c. 3065 G > T,p. G1022V heterozygosis missense mutation on the COL1A1 gene,which caused osteogenesis imperfecta type II ;it was already reported on the HGMD. Conclusions (1) The high-risk fetus suffer with osteogenesis imperfecta -Ⅱ ,which should be induced labour (the fetus had been induced labour already. The result of prenatal gene diagnosis was completely accordance with the result of

  7. Four patients with Sillence type I osteogenesis imperfecta and mild bone fragility, complicated by left ventricular cardiac valvular disease and cardiac tissue fragility caused by type I collagen mutations.

    Science.gov (United States)

    Vandersteen, Anthony M; Lund, Allan M; Ferguson, David J P; Sawle, Philip; Pollitt, Rebecca C; Holder, Susan E; Wakeling, Emma; Moat, Neil; Pope, F Michael

    2014-02-01

    Osteogenesis imperfecta (OI) type I is a hereditary disorder of connective tissue (HDCT) characterized by blue or gray sclerae, variable short stature, dentinogenesis imperfecta, hearing loss, and recurrent fractures from infancy. We present four examples of OI type I complicated by valvular heart disease and associated with tissue fragility. The diagnosis of a type I collagen disorder was confirmed by abnormal COL1A1 or COL1A2 gene sequencing. One patient was investigated with electrophoresis of collagens from cultured skin fibroblasts, showing structurally abnormal collagen type I, skin biopsy showed unusual histology and abnormal collagen fibril ultra-structure at electron microscopy. The combined clinical, surgical, histological, ultra-structural, and molecular genetic data suggest the type I collagen defect as contributory to cardiac valvular disease. The degree of tissue fragility experienced at cardiac surgery in these individuals, also reported in a small number of similar case reports, suggests that patients with OI type I need careful pre-operative assessment and consideration of the risks and benefits of cardiac surgery. PMID:24311407

  8. Four patients with Sillence type I osteogenesis imperfecta and mild bone fragility, complicated by left ventricular cardiac valvular disease and cardiac tissue fragility caused by type I collagen mutations.

    Science.gov (United States)

    Vandersteen, Anthony M; Lund, Allan M; Ferguson, David J P; Sawle, Philip; Pollitt, Rebecca C; Holder, Susan E; Wakeling, Emma; Moat, Neil; Pope, F Michael

    2014-02-01

    Osteogenesis imperfecta (OI) type I is a hereditary disorder of connective tissue (HDCT) characterized by blue or gray sclerae, variable short stature, dentinogenesis imperfecta, hearing loss, and recurrent fractures from infancy. We present four examples of OI type I complicated by valvular heart disease and associated with tissue fragility. The diagnosis of a type I collagen disorder was confirmed by abnormal COL1A1 or COL1A2 gene sequencing. One patient was investigated with electrophoresis of collagens from cultured skin fibroblasts, showing structurally abnormal collagen type I, skin biopsy showed unusual histology and abnormal collagen fibril ultra-structure at electron microscopy. The combined clinical, surgical, histological, ultra-structural, and molecular genetic data suggest the type I collagen defect as contributory to cardiac valvular disease. The degree of tissue fragility experienced at cardiac surgery in these individuals, also reported in a small number of similar case reports, suggests that patients with OI type I need careful pre-operative assessment and consideration of the risks and benefits of cardiac surgery.

  9. Myths about OI (Osteogenesis Imperfecta)

    Science.gov (United States)

    ... Subscribe to the Breakthrough Newsletter or E-News Myths about OI In the United States, any disease ... successful, and satisfying lives. The following list of myths describes some of the most common misinformation about ...

  10. Fast Facts on Osteogenesis Imperfecta

    Science.gov (United States)

    ... a negative result could mean that either a collagen type I mutation is present but was not detected ... mutation in a gene coding for type I collagen (Types I, II, III, and IV in the following ...

  11. Genetics Home Reference: osteogenesis imperfecta

    Science.gov (United States)

    ... proteins that are used to assemble type I collagen. This type of collagen is the most abundant protein in bone, skin, ... gene. These genetic changes reduce the amount of type I collagen produced in the body, which causes bones to ...

  12. Child Abuse or Osteogenesis Imperfecta?

    Science.gov (United States)

    ... bodies to make either too little type 1 collagen or poor quality type 1 collagen. The result is bones that break ... evident at birth. • Small stature with underdeveloped lungs. • Collagen is improperly formed. Type III (Progressive) • Progressive bone deformity, often severe. • Bones ...

  13. An overlapping phenotype of Osteogenesis imperfecta and Ehlers-Danlos syndrome due to a heterozygous mutation in COL1A1 and biallelic missense variants in TNXB identified by whole exome sequencing.

    Science.gov (United States)

    Mackenroth, Luisa; Fischer-Zirnsak, Björn; Egerer, Johannes; Hecht, Jochen; Kallinich, Tilmann; Stenzel, Werner; Spors, Birgit; von Moers, Arpad; Mundlos, Stefan; Kornak, Uwe; Gerhold, Kerstin; Horn, Denise

    2016-04-01

    Osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) are variable genetic disorders that overlap in different ways [Cole 1993; Grahame 1999]. Here, we describe a boy presenting with severe muscular hypotonia, multiple fractures, and joint hyperflexibility, features that are compatible with mild OI and hypermobility type EDS, respectively. By whole exome sequencing, we identified both a COL1A1 mutation (c.4006-1G > A) inherited from the patient's mildly affected mother and biallelic missense variants in TNXB (p.Val1213Ile, p.Gly2592Ser). Analysis of cDNA showed that the COL1A1 splice site mutation led to intron retention causing a frameshift (p.Phe1336Valfs*72). Type 1 collagen secretion by the patient's skin fibroblasts was reduced. Immunostaining of a muscle biopsy obtained from the patient revealed a clear reduction of tenascin-X in the extracellular matrix compared to a healthy control. These findings imply that the combination of the COL1A1 mutation with the TNXB variants might cause the patient's unique phenotype. PMID:26799614

  14. Avaliação clínica, radiográfica e laboratorial de pacientes com osteogênese imperfeita Clinical, radiographic and laboratory evaluation of patients with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Cláudio Santili

    2005-08-01

    Full Text Available OBJETIVOS: A osteogênese imperfeita (OI é uma doença genética, caracterizando-se por alterações no colágeno do tipo I, que determinam um espectro amplo de alterações clínicas, como a dentinogênese imperfeita e escleras azuladas. O objetivo deste estudo é estabelecer uma correlação prática no diagnóstico diferencial intergrupos dentro da classificação de Sillence et al. (1979. MÉTODOS: Foram avaliados 22 pacientes mediante critérios clínicos e radiográficos. Após, a subdivisão de acordo com os tipos de Sillence et al. (1979, os pacientes foram também submetidos à avaliação laboratorial e à densitometria óssea. RESULTADOS: Os dados significantes para diferenciação entre os tipos da doença foram a estatura, o número total de fraturas por indivíduo e a densitometria óssea. O cálcio sérico não diferencia os tipos da doença. CONCLUSÕES: Características como a deambulação, a estatura e a densitometria óssea podem auxiliar na diferenciação entre os subtipos dos portadores da doença, repercutindo diretamente no estabelecimento do seu prognóstico.BACKGROUND: Osteogenesis imperfecta is a genetic disorder characterized by defects in type I collagen. The main symptom is bone fragility and susceptibility to fractures. Other clinical findings are dentinogenesis imperfecta, blue sclera, early deafness and joint laxity. The purpose of this paper is to establish a practical relationship of the clinical differences between the Sillence's groups. METHODS: 22 patients were classified according to Sillence et al criteria and submitted to laboratory tests including blood calcium level and bone densitometry. RESULTS: All clinical and laboratory differences were discussed in the text. CONCLUSIONS: Differences such as results that were found in walking ability, height and bone densitometry were significant and may help to classify patients and to establish prognosis.

  15. Diagnóstico pré-natal e parto transpelviano na osteogênese imperfeita: relato de caso Prenatal diagnosis and vaginal delivery in osteogenesis imperfecta: a case report

    Directory of Open Access Journals (Sweden)

    Alex Sandro Rolland de Souza

    2006-04-01

    Full Text Available A osteogênese imperfeita é doença do tecido conjuntivo devida a anormalidades quantitativas ou qualitativas do colágeno tipo I, transmitida geneticamente, por gene autossômico dominante ou recessivo, que determina fragilidade óssea. Relata-se o caso clínico de paciente de 19 anos, primigesta, encaminhada ao setor de medicina fetal com ultra-sonografia pregressa evidenciando encurtamento de extremidades fetais. Na avaliação morfológica, identificou-se contorno craniano irregular com deformidade à compressão do pólo cefálico, membros com rizo e mesomelia, rarefação óssea e encurvamento de ossos longos (fraturas. A paciente evoluiu com parto transpelviano na 35ª semana de gestação. O recém-nascido apresentou Apgar de 6 no 1ª minuto e 8 no 5ª minuto, sexo masculino, pesando 1.990 gramas. Observado crânio irregular, ossificação diminuída, esclera azulada e fraturas consolidadas com deformidades em todos os membros. O recém-nascido apresentou boa evolução neonatal, recebendo alta hospitalar em boas condições. O diagnóstico pré-natal é de grande importância para adequado acompanhamento da gravidez e a via de parto transpelviana não ocasionou piora do prognóstico neonatal, pois não foram diagnosticadas fraturas recentes.Osteogenesis imperfecta is a connective tissue disorder due to quantitative and qualitative anomalies in type 1 collagen, genetically transmitted by a dominant or recessive autosomal gene, leading to bone fragility. We report a case of a 19-year-old G1 PO patient referred to our institution following a screening ultrasound that demonstrated short limb fetal extremities. A level 3 scan was performed which evidenced an irregular cranial shape and compression of the cephalic pole with moderate transducer pressure. Limb shortening, decreased echoes and fractures of long bones were found on our scan evaluation. A vaginal delivery occurred at 35 weeks of gestation. The male newborn, weighing 1.990 grams

  16. Screening and analysis of a new mutation of COL1A1 gene in a family with osteogenesis imperfecta%一个成骨不全家系COL1A1基因的突变筛查

    Institute of Scientific and Technical Information of China (English)

    白雪; 李克秋; 任秀智; 何晓波; 王毅; 官士珍; 景亚青; 李光

    2014-01-01

    Objective To investigate mutation of COL1A1 gene and analyze the relationship between genotype and clinical phenotype in a family with osteogenesis imperfecta (OI).Methods The family history of an OI pedigree,along with clinical data,was collected.Blood samples from the proband and his families,as well as 50 normal controls,were collected.Mutation of COL1A1 gene was screened using PCR-high resolution melting (PCR-HRM) and validated by sequencing.Results PCR-HRM method showed an abnormal result in proband COL1A1 33_34 exons,which Tm was 87.7℃,in contrast to the normal control (wt) Tm of 87.9 ℃ ± 0.06℃.There was a significant difference between the proband and the normal control with the standardization curve and the difference curves.DNA sequencing showed that COL1A1 gene exons 33_34 has lost a C base (c.2321delC),which resulted in a frameshift mutation and caused an premature termination codon (UAA) at amino acid 334,i.e.,p.Pro774LeufsX334.The father and grandfather of the proband,both suffered from OI,were verified to be heterozygous for the same mutation.The same mutation was not found in 50 normal controls.Database search confirmed this to be a novel mutation.Pedigree analysis suggested that it has an autosomal dominant inheritance.The proband and patients from the family were clinically diagnosed as OI type Ⅰ.Conclusion The study has identified a novel mutation of COL1A1 gene,c.2321delC.This frameshift mutation has caused a premature stop codon and reduced collagen type Ⅰ synthesis,characterized by a lighter OI clinical phenotype.%目的 筛查1个成骨不全(osteogenesis imperfecta,OI)家系中COL1A1基因的突变,并分析基因型与临床表型的关系.方法 收集先证者及家系成员临床资料,采集先证者、随诊家属及50名正常对照的外周血标本,应用PCR-高分辨率熔解曲线(high resolution melting,HRM)分析筛查COL1A1基因突变,基因测序确定突变位点.结果 PCR-HRM分析显示,先证者COL1A1

  17. Sobrevida de uma haste intramedular extensível (HIMEX no tratamento de crianças com ostegênese imperfeita Survival rates of the HIMEX extensible nail in the treatment of children with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    William Dias Belangero

    2010-01-01

    Full Text Available OBJETIVO: avaliar o desempenho da haste extensível ancorada por ganchos (HIMEX em deformidades da osteogênese imperfeita (OI. MÉTODOS: Todas as crianças operadas com HIMEX entre 1990 - 2004. Foi comparado o número de fraturas, reaparecimento de deformidades e capacidade de deambulação antes e após a HIMEX; incidência de migração e sobrevida da haste por curvas de sobrevivência. RESULTADOS: 14 pacientes (2 a 18 anos, oito do sexo feminino, incluindo 46 procedimentos, 39 primários e sete re-operações. Idade média na primeira fratura de 148,21 dias e média de 42,6 fraturas/paciente pré colocação da HIMEX. Dos 46 procedimentos, 28 no fêmur e 18 na tíbia. Tempo médio de seguimento de 80,21 ± 36,71 meses. Houve diminuição significativa de fraturas/paciente (0,78 e melhora na deambulação em sete dos 14 pacientes. Porcentagem de re-operação de 18% e migração do implante em 12% (05/39. 80 % dos implantes in situ até 108 meses. Implantes na tíbia tiveram sobrevida significativamente menor que os do fêmur. O tipo da OI e a idade na época da cirurgia não influenciaram significativamente a incidência de re-operação. CONCLUSÃO: A HIMEX levou à redução significativa no número de fraturas, incidência menor de migração e sobrevida maior da haste do que a referida na literatura.OBJECTIVE: To evaluate the performance of an extensible nail with hooks, named HIMEX, in osteogenesis imperfecta (OI deformities. METHODS: All child patients were operated on with HIMEX from 1990 to 2004. The number of fractures, reappearance of deformities, improvement of motor development before and after the use of HIMEX, and the incidence of the migration and nail survival were compared. RESULTS: Fourteen patients, with ages from 2 to 18 years, including 8 females, underwent 46 procedures, 39 primary and 7 re-operations. The average age at the first fracture was 148.21 days, and there was an average of 42.6 fractures per patient prior to

  18. Amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    K P Mahesh

    2012-01-01

    Full Text Available Amelogenesis imperfecta (AI represents a group of developmental disorder of teeth structure, genomic in origin, which affects the structure and clinical appearance of enamel of all or nearly all the teeth, and which may be associated with morphologic or biochemical changes elsewhere in the body. It can be hypoplastic, hypomineralized, or both. Teeth affected may be discoloured, sensitive, or prone to disintegration. A case of yellow brown discoloration in a hindu female aged 26, reported with same chief complaint. On examination of the patient, generalized yellowish brown discoloration of the teeth was seen. Radiographic and histopathologic examination confirms the diagnosis of AI.

  19. Heart disease in patients with osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Ashournia, Hamoun; Johansen, Frank Ted; Folkestad, Lars;

    2015-01-01

    described, less is known about the effects of decreased collagen on other organs. In the heart, collagen type 1 is present in the heart valves, chordae tendineae, annuli fibrosi and the interventricular septum. It is thus likely that the heart is affected in OI. OBJECTIVES: The aim of this systematic...... commonly reported heart diseases amongst the patients with OI were valvulopathies and increased aortic diameter. Findings in the large case series and the cross-sectional studies were broadly similar to each other. CONCLUSION: The findings support the hypothesis that patients with OI have increased risk of...... heart disease compared to healthy controls. It is biologically plausible that patients with OI may have an increased risk of developing heart disease, and valve disease in particular....

  20. Planning for Your Child's Surgery (Osteogenesis Imperfecta)

    Science.gov (United States)

    ... pill, tablet, or liquid. Some medicines have a bad taste. Find out ahead of time if your ... parents include conference calls, contributing to a class project or sending e-mails to the class. Many ...

  1. PCR-HRM分析筛查成骨不全一家系患儿基因突变%PCR-HRM Analysis for Gene Mutation Screening in a Child with Osteogenesis Imperfecta

    Institute of Scientific and Technical Information of China (English)

    白雪; 李克秋; 任秀智; 何晓波; 王毅; 官士珍; 景亚青; 李光

    2014-01-01

    目的:采用PCR-高分辨率熔解曲线(HRM)分析筛查成骨不全(OI)一家系患儿(先证者)COL1A1基因突变位点,探讨其基因型与临床表型的联系。方法对先证者进行家族史及临床资料的调查,采集先证者、家属及50名正常对照者血液标本,应用PCR-HRM分析筛查先证者及正常对照者COL1A1基因突变,基因测序确证突变位点。结果先证者COL1A1基因17外显子筛查结果异常,其熔解温度(Tm)值比正常对照者Tm值低约0.4℃。先证者与正常对照者的标准熔解曲线及差异熔解曲线均有明显差异。测序结果为c.1138G>A,突变导致380位氨基酸由甘氨酸(Gly)变成丝氨酸(Ser):p.(Gly 380 Ser),为错义突变。先证者父亲、祖母均具有相同突变位点。先证者母亲及正常对照者基因测序结果无此突变。该突变在中国人群中未见报道。该家系遗传特征为常染色体显性遗传,先证者临床诊断为Ⅳ型OI,临床表型较严重。结论 PCR-HRM分析是有效的OI基因筛查新方法。COL1A1基因c.1138G>A突变在中国人群中为新发现的突变位点。α螺旋结构域Gly被替换可能导致较严重的临床表型。%Objective To investigate COL1A1 gene mutation by PCR-high resolution melting (PCR-HRM) and an-alyze the correlation between genotype and clinical phenotype in a child (proband) with osteogenesis imperfecta (OI). Methods The family history of OI pedigree along with the clinical data was collected. Blood samples from the proband and his family members, as well as 50 normal controls, were collected. The mutation of COL1A1 gene was screened using PCR-HRM and validated by the gene sequence. Results The detection of PCR-HRM showed the abnormal result of COL1A1 17 exon in proband with a lower melting temperature (Tm) value than that of normal controls by 0.4℃. There were signifi-cant differences in the standardization melting curve and the different

  2. COL1A1基因新的剪接突变c.3208G>A导致Ⅰ型成骨不全一家系%A novel splicing mutation in COL1A1 gene caused type Ⅰ osteogenesis imperfecta in a Chinese family

    Institute of Scientific and Technical Information of China (English)

    赵鼎; 杨俊梅; 郭振欣; 李瑞

    2014-01-01

    目的 探讨一个成骨不全家系中COL1A 1基因的突变.方法 收集一个成骨不全家系的临床资料,采用聚合酶链反应以及直接测序法对所有成员进行COL1A1基因突变的检测,同时在20名健康亲属以及200名非亲属对照中对发现的突变进行检测.结果 RNA剪接分析发现一个c.3208G>A突变,后者造成了一种新的剪接位点,从而导致移码突变.在患者的健康亲属及正常对照中未发现同样的突变.结论 COL1A1基因突变是导致成骨不全的主要原因之一,本研究结果进一步丰富了Ⅰ型胶原基因的突变谱.%Objective To study a family affected with osteogenesis imperfecta for potential mutations in COL1A1 gene.Methods Clinical data of an affected family was collected.Potential mutation of the COL1A1 gene was screened using polymerase chain reaction and direct sequencing.Suspected mutation was detected in 20 unaffected relatives and 200 unrelated healthy controls.Results Analysis of RNA splicing has revealed a c.3208G/A mutation,which created a new splice sites and led to a frameshift mutation.The same mutation was not detected in the unaffected relatives or the 200 healthy controls.Conclusion Mutations of the COL1A1 gene are one of the major causes of osteogenesis imperfecta in Chinese population.Our finding has enriched the mutation spectrum of type Ⅰ collagen genes.

  3. Genetic Aspects of Dentinogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Elza Ibrahim Auerkari

    2015-10-01

    Full Text Available Dentinogenesis Imperfecta (DI is a hereditary, simple autosomal dominant disorder showing abnormalities in the dentin of the developing teeth and occurring at a rate of about 1 in 8000 births. The expression of DI shows a high penetrance and a low mutation rate. Two main types of DI appear to exist: type I which is the defect associated with osteogenesis imperfecta, and type II which is the classical hereditary opalescent dentin. The formerly proposed DI type III appears to be only a modified expression of the same gene as in the classical DI type II. Any gene therapy type of treatment is unrealistic for adolescent patients who already exhibit the symptoms. However, there is a good prospect for early screening since DI is inherited as a dominant disorder, and known trail from parents or siblings is a strong indication for later exposure to DI. At present there are no practical means to correct the genetic defect or to avoid the symptoms. Nevertheless, screening provides an early warning and helps to guide protective and restorative treatment so early that maximum amount of the natural dentition can be retained.

  4. Amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Aldred Michael

    2007-04-01

    Full Text Available Abstract Amelogenesis imperfecta (AI represents a group of developmental conditions, genomic in origin, which affect the structure and clinical appearance of enamel of all or nearly all the teeth in a more or less equal manner, and which may be associated with morphologic or biochemical changes elsewhere in the body. The prevalence varies from 1:700 to 1:14,000, according to the populations studied. The enamel may be hypoplastic, hypomineralised or both and teeth affected may be discoloured, sensitive or prone to disintegration. AI exists in isolation or associated with other abnormalities in syndromes. It may show autosomal dominant, autosomal recessive, sex-linked and sporadic inheritance patterns. In families with an X-linked form it has been shown that the disorder may result from mutations in the amelogenin gene, AMELX. The enamelin gene, ENAM, is implicated in the pathogenesis of the dominant forms of AI. Autosomal recessive AI has been reported in families with known consanguinity. Diagnosis is based on the family history, pedigree plotting and meticulous clinical observation. Genetic diagnosis is presently only a research tool. The condition presents problems of socialisation, function and discomfort but may be managed by early vigorous intervention, both preventively and restoratively, with treatment continued throughout childhood and into adult life. In infancy, the primary dentition may be protected by the use of preformed metal crowns on posterior teeth. The longer-term care involves either crowns or, more frequently these days, adhesive, plastic restorations.

  5. [Distraction osteogenesis in orthopaedics

    NARCIS (Netherlands)

    Baat, P. de; Baat, C. de; Bessems, J.H.

    2008-01-01

    For several decades, distraction osteogenesis has been applied in orthopaedics for lengthening limbs. Other indications for distraction osteogenesis in orthopaedics are nonunions, open fractures, oncologic defects, and ankle osteoarthritis. The main principle of distraction osteogenesis is that, wit

  6. Identification of a novel splicing mutation in COL1A1 gene in a Chinese family affected with type Ⅰ osteogenesis imperfecta%COL1A1基因中一个导致Ⅰ型成骨不全的新剪接突变c.3208G>A分析

    Institute of Scientific and Technical Information of China (English)

    宋银森; 金湘东; 孔京慧; 赵鼎; 郭振欣

    2014-01-01

    目的 探讨COL1A1基因中一个新突变c.3208G>A导致Ⅰ型成骨不全的致病机理.方法 应用标准的方法提取外周血全基因组DNA,PCR扩增基因的整个编码区域和内含子-外显子边界,应用ABI 3100/3130测序仪对PCR产物进行直接测序.从患者的EB病毒转化永生B细胞系中提取全RNA,用寡(dT) 18引物合成第一链cDNA,对PCR产物直接测序或者用TA克隆质粒DNA测序.结果 在一个Ⅰ型成骨不全大家庭中检测到一种位于COL1A1基因上的新突变c.3208G>A,为剪接突变.结论 发现了COL1A1基因中的新的剪接突变c.3208G>A.%Objective To investigate the genetic cause for a large family affected with type Ⅰ osteogenesis imperfecta.Methods Genomic DNA was extracted from peripheral venous blood samples.The entire coding region and intron-exon boundaries of the COL1A1 gene were subjected to PCR amplification and direct sequencing.Total RNA was also extracted from immortalized B cell lines from the patients,with the first strand of cDNA synthesized with an oligo(dT)18 primer.The PCR products were directly sequenced using the TA cloned plasmid.Results A c.3208G> A mutation has been identified in the COL1A1 gene,which can alter the splicing pattern of mRNA.Conclusion A novel splicing mutation c.3208G>A of the COL1A1 gene probably underlies the disease.

  7. Distraction osteogenesis.

    Science.gov (United States)

    Sidman, James; Tatum, Sherard Austin

    2014-02-01

    James Sidman, MD, and Sherard A. Tatum, MD, address the following questions for discussion and debate. Is neonatal distraction osteogenesis (DO) better than lip-tongue adhesion or tracheotomy for micrognathic airway compromise? What role does DO have in adult orthognathic surgery situations? In monobloc and Le Fort III procedures, are internal or external devices preferable? What role does DO play in craniofacial microsomia? Is endoscopic DO better than open procedures for synostosis management? How has your technique changed or evolved over the past 5 years and what has doing this technique taught you?

  8. Genetic screening of a pedigree with osteogenesis imperfecta type Ⅰand identification of a novel mutation in COL1A2 pathogenic gene%成骨不全Ⅰ型家系的基因检测和COL1A2基因新突变的致病性鉴定

    Institute of Scientific and Technical Information of China (English)

    李荣; 郭源平; 潘敬新; 郭奕斌

    2015-01-01

    To uncover the molecular pathogenic mechanism of congenital osteogenesis imperfecta (OI) type I, all the 103 exons of the COL1A1 (Collagen, type Ⅰ, alpha 1) and COL1A2 (Collagen, type Ⅰ, alpha 2) genes in a child with OI type Ⅰ were screened using PCR-DNA direct sequencing. The results showed no pathological mutation in COL1A1 gene, but a novel mutation c.946G>T/p.G316C in the exon 19 of COL1A2 gene, which was inherited from her father. This mutation was not found in her mother and other six phenotypically normal relatives. By denaturing high perfor-mance liquid chromatography (DHPLC) screening, the abnormal double-peak was visualized in PCR products of exon 19 of COL1A2 gene in the proband and her father, while the normal single-peak was shown in those of her mother and all the healthy controls. Using allele specific amplification (ASA) screening, a specific band of 391 bp in COL1A2 exon 19 was amplified only in the proband and her father, but not in other samples. The amino acid encoded by the mutation site is evolutionarily highly conserved, and this mutation was a“damaging”or“probably damaging”factor to OI type Ⅰ, based on the predicting results using SIFT and Polyphen-2 softwares. In conclusion, the novel c.946G>T/p.G316C mutation in COL1A2 gene is a pathogenic mutation that could result in OI type Ⅰ. If the couple wants to get pregnant again, it is necessary to screen the mutation site in COL1A2 gene through the prenatal genetic diagnosis in the first trimester or through preimplantation genetic diagnosis (PGD) in the progestation.%为了揭示成骨不全(Osteogenesis imperfecta, OI)Ⅰ型家系的分子遗传学发生机制,文章采用PCR-DNA直接测序法,对患儿 COL1A1和 COL1A2基因共103个外显子(E)进行突变检测。结果显示:患儿 COL1A1基因未发现任何病理性突变,而在 COL1A2基因 E19内发现一新的杂合错义突变(p.G316C),该突变来自其父,而其母正常,其他表型正常的6位

  9. Dentinogenesis imperfecta associated with short stature, hearing loss and mental retardation: a new syndrome with autosomal recessive inheritance?

    Science.gov (United States)

    Cauwels, R G E C; De Coster, P J; Mortier, G R; Marks, L A M; Martens, L C

    2005-08-01

    The follow-up history and oral findings in two brothers from consanguineous parents suggest that the association of dentinogenesis imperfecta (DI), delayed tooth eruption, mild mental retardation, proportionate short stature, sensorineural hearing loss and dysmorphic facies may represent a new syndrome with autosomal recessive inheritance. Histological examination of the dentin matrix of a permanent molar from one of the siblings reveals morphological similarities with defective dentinogenesis as presenting in patients affected with Osteogenesis Imperfecta (OI), a condition caused by deficiency of type I collagen. A number of radiographic and histological characteristics, however, are inconsistent with classical features of DI. These findings suggest that DI may imply greater genetical heterogeneity than currently assumed.

  10. Prosthodontic rehabilitation of dentinogenesis imperfecta.

    Science.gov (United States)

    Goud, Anil; Deshpande, Saee

    2011-04-01

    Dentinogenesis imperfecta and its prosthodontic management is a challenging task. Treatment protocol varies according to clinical case. Although various reports in the literature suggest general guidelines for treatment planning, the present case report describes a full mouth rehabilitation of a young patient with dentinogenesis imperfecta treated by maxillary fixed partial dentures and mandibular fiber reinforced overdenture with metal occlusal surfaces.

  11. Prosthodontic rehabilitation of dentinogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Anil Goud

    2011-01-01

    Full Text Available Dentinogenesis imperfecta and its prosthodontic management is a challenging task. Treatment protocol varies according to clinical case. Although various reports in the literature suggest general guidelines for treatment planning, the present case report describes a full mouth rehabilitation of a young patient with dentinogenesis imperfecta treated by maxillary fixed partial dentures and mandibular fiber reinforced overdenture with metal occlusal surfaces.

  12. Fracture Rates and Fracture Sites in Patients With Osteogenesis Imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Ersbøll, Annette Kjaer;

    2016-01-01

    , with a peak during the toddler and adolescent years (incidence rate [IR] 233.9 per 1000 person years), fewer fractures during adulthood (IR 84.5 per 1000 person years), and increased fracture rates in older women (IR 111.9 per 1000 person years). This is the largest register-based nationwide study...... years. In comparison, 709 persons in the reference population experienced a total of 1018 fractures during follow-up. Both male and female patients with OI had an increased fracture rate throughout their life. The fracture rate ratio for participants aged 0 to 19 years was 10.7, for participants aged 20...... to 54 years 17.2, and for participants aged 55 years and over 4.1 when compared to the reference population. The highest fracture rate was seen in males with OI aged 0 to 19 years (257 fractures per 1000 person-years). The fractures appear to follow the same pattern as in the general population...

  13. Forstørret nakkefold kan ses ved osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Schönewolf-Greulich, Bitten; Skibsted, Lillian; Maroun, Lisa Leth;

    2011-01-01

    present case, ultrasound scanning at 13 weeks of gestation showed a NT of 3.2 mm and no other pathological findings. At 20 weeks a severe skeletal dysplasia was diagnosed by ultrasound. The pathology report of the aborted foetus indicated OI, and DNA analysis confirmed a COL1A1 mutation....

  14. Amelogenesis imperfecta: a clinician's challenge.

    Science.gov (United States)

    Chamarthi, V; Varma, B R; Jayanthi, M

    2012-01-01

    Defective enamel formation can be explained as defects occurring at the stages of enamel formation. Quantitative defects in matrix formation leads to hypoplastic form of amelogenesis imperfecta. Inadequate mineralization of matrix leads to hypocalcification and hypomaturation variants. The demarcation of matrix formation and mineralization is not so distinct. This paper describes a case of a 7-year-old boy with amelogenesis imperfecta - Type IA i.e., hypoplastic pitted autosomal dominant.

  15. 成骨不全症患者COL1A1/2致病突变谱和基因诊断研究%Spectrum of COL1A1/2 mutations and gene diagnosis in Chinese patients with osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    赵秀丽; 肖继芳; 汪涵; 任秀智; 高劲松; 吴易阳; 卢超霞; 张学

    2015-01-01

    目的 在成骨不全症(OI)患者中鉴定Ⅰ型胶原基因(COL1A1和COL1A2)致病突变,构建中国人OI致病基因突变谱,并在此基础上完成OI高危胎儿的产前基因诊断.方法 应用酚/氯仿法提取先证者及家系成员外周血基因组DNA,联合应用聚合酶链反应(PCR)-Sanger DNA测序和靶向高通量测序技术对200例OI先证者进行COL1A1/2编码区及外显子/内含子衔接区的DNA序列分析;采用PCR-高分辨熔解曲线(HRM)技术对先证者及其家系成员进行突变验证;通过PCR-测序对散发病例的父母样本进行突变检测,进而确定突变来源;联合应用PCR-测序和微卫星标记等位基因分析的方法进行胎儿产前基因诊断.结果 在158例先证者中,发现COL1A1/2基因致病突变125种,包含COL1A1突变74种(91例),COL1A2突变51种(67例),阳性检出率79% (158/200);发现新突变63种,包括33种COL1A1突变和30种COL1A2突变.在上述125种COL1A1/2基因突变中,13种突变分别在2例以上先证者中重复出现(其中6种突变重复出现4次以上),合计检出46次,检出率为29.11% (46/158);完成产前基因诊断74例,其中包括患儿40例,正常胎儿34例.结论 建立基于Sanger DNA测序、靶向高通量测序和PCR-高分辨熔解曲线分析技术的OI基因诊断平台.在中国人群中,构建了OI相关COL1A1/2基因致病突变谱,并在此基础上完成大样本OI患者和高危胎儿的基因诊断.%Objective To identify mutations of the type Ⅰ collagen genes (COL1A1 and COL1A2) in the affected with osteogenesis imperfecta (OI) , to establish the spectrum of COL1A1/2 mutations in Chinese OI patients, and to provide prenatal gene diagnosis to the fetuses at high risk.Methods Genomic DNA was extracted from peripheral blood by the standard SDS-proteinase K-phenol/chloroform method.All the coding regions and exon/intron boundaries of COL1A1/2 were screened in 200 OI cases by conventional Sanger sequencing and targeted next

  16. The application of high-resolution melting analysis in gene mutation screening of osteogenesis imperfecta%高分辨率熔解曲线分析在成骨不全相关基因突变筛查中的应用

    Institute of Scientific and Technical Information of China (English)

    白雪; 李克秋; 李光; 任秀智; 常小丽; 张天可; 官士珍; 王毅

    2015-01-01

    Objective To explore the application of high-resolution melting analysis (HRMA) in gene mutations screening of osteogenesis imperfecta(OI).Methods Clinical data of five children with OI was collected from March to December 2012 in Tianjin Hospital.Blood samples from five children with OI and their parents with a family history of OI were collected as well as normal controls.All exons and their flanking sequences of COL1 A1 and COL1 A2 gene were screened using PCR-HRMA and validated by the gene sequencing.Results PCR-HRMA showed abnormal results from five children in the COL1Al gene exon l 1,exon 39,exon 8 and the COL1A2 gene exon 19 screening area,respectively.Melting curves of children with OI were differences from normal controls,which showed the mutations of genes.Standard melting curve showed five children with mutations of heterozygous mutation.Sequencing analysis showed that children with COL1A1 gene mutation,c.768dupC,c.2644C > T,c.635G > A and COL1A2 gene mutation c.982G > A,c.948C >T,respectively.COL1A1 gene mutation caused a premature stop codon in children 1,2 and clinical diagnosis with type Ⅰ OI.Genetic mutations in children 3,4 with OI in alpha helix structure domain Gly alternative,and clinical diagnosis with type Ⅳ O1.Children 5 gene mutation was nonsense mutations.This variation is not the cause of OI,Which possible causes need to be researched.Conclusions PCR-HRMA has a low cost,easy operation,fast,high flux,pollution-free advantages.PCR-HRMA is a new effective method for OI mutation screening.The study found a new mutation of COL1 A1 gene,c.768dupC.%目的 探讨高分辨率熔解曲线分析(HRMA)在成骨不全(OI)相关基因突变筛查中的应用价值.方法 收集2012年3月至12月于天津医院住院的5例OI患儿临床资料.采集患儿、有家族史患儿父母及查体健康者(正常对照)血液标本,PCR-HRMA筛查患儿COLlAl/COLlA2基因所有外显子及其侧翼序列,基因测序确定突变位点.有家族

  17. Esthetic reconstruction of teeth in patient with dentinogenesis imperfecta--a case report.

    Science.gov (United States)

    Knezević, Alena; Tarle, Zrinka; Pandurić, Vlatko

    2006-03-01

    Dentinogenesis imperfecta (DI) is the result of a dominant genetic defect and affects both the deciduous and permanent dentitions. It is characterized by opalescent teeth composed of irregularly formed and undemineralized dentin which obliterates pulp chamber and root canal. DI can appear as a separate disorder or with osteogenesis imperfecta (OI). The teeth with DI show a grayish-blue to brown hue with dislodged enamel, dysplastic dentine with irregular dentinal tubules and interglobular dentine, short roots and pulpal obliteration, which all may lead to rapid and extensive attrition which require adequate crown reconstruction. The aim of this study was to show a reconstruction of frontal teeth in upper jaw with direct composite veneers in young adult patient with DI.

  18. Dentinogenesis imperfecta type I: A case report with literature review on nomenclature system.

    Science.gov (United States)

    Devaraju, D; Devi, Bk Yashoda; Vasudevan, Vijeev; Manjunath, V

    2014-09-01

    Dentinogenesis imperfecta (DI) is an inherited disorder affecting dentin. Defective dentin formation results in discolored teeth that are prone to attrition and fracture. Mutation in dentin sialophosphoprotein (DSPP) has been found to cause the dentin disorders DI - I and II (shields II and III). Early diagnosis and treatment of DI is recommended as it may prevent or intercept deterioration of the teeth and occlusion and improve esthetics. Here, we report a case with characteristic clinical, radiological and histological features of DI-I. The etiology and classification followed in literature is confusing since dentinoenamel junction (DEJ) in DI seems to be structurally and functionally normal and DI is clearly a disorder distinct from osteogenesis imperfecta (OI), but we still relate etiology of DI to DEJ and follow Shields classification. Therefore, we have briefly reviewed etiology and nomenclature system of DI.

  19. Dentinogenesis imperfecta type I: A case report with literature review on nomenclature system

    Directory of Open Access Journals (Sweden)

    D Devaraju

    2014-01-01

    Full Text Available Dentinogenesis imperfecta (DI is an inherited disorder affecting dentin. Defective dentin formation results in discolored teeth that are prone to attrition and fracture. Mutation in dentin sialophosphoprotein (DSPP has been found to cause the dentin disorders DI - I and II (shields II and III. Early diagnosis and treatment of DI is recommended as it may prevent or intercept deterioration of the teeth and occlusion and improve esthetics. Here, we report a case with characteristic clinical, radiological and histological features of DI-I. The etiology and classification followed in literature is confusing since dentinoenamel junction (DEJ in DI seems to be structurally and functionally normal and DI is clearly a disorder distinct from osteogenesis imperfecta (OI, but we still relate etiology of DI to DEJ and follow Shields classification. Therefore, we have briefly reviewed etiology and nomenclature system of DI.

  20. [Cytokines and osteogenesis].

    Science.gov (United States)

    Fujiwara, Makoto; Ozono, Keiichi

    2014-06-01

    Many cytokines associate with proliferation, differentiation and activation of osteoblasts which have an important role in osteogenesis. TGF-β, BMP, IGF, FGF, Hedgehog, Notch, IL and WNT signaling pathways and their inhibitors have been revealed to correlate to osteogenesis, and those gene mutations have been shown to cause various bone disorders. It has been suggested that there are common pathways or crosstalk in these cytokine signaling each other, but mechanism of their complicated regulation on osteogenesis has been unclear. It was expected that the knowledge about these cytokines will apply to clinical therapies of bone diseases. PMID:24870835

  1. Dentinogenesis imperfecta: endodontic implications. Case report.

    Science.gov (United States)

    Pettiette, M T; Wright, J T; Trope, M

    1998-12-01

    Dentinogenesis imperfecta is a hereditary disorder resulting in defective dentin in both the primary and secondary dentitions. The complications of dentinogenesis imperfecta are difficult to manage and provide a challenge to the dentist. This case report concerns treating an African American patient with dentinogenesis imperfecta who appeared for treatment with endodontic pathosis. It illustrates the need for appropriate and timely restorative treatment to prevent pulpal pathosis. Also demonstrated is the difficulty of endodontically treating dentinogenesis imperfecta teeth because of pulpal obliteration and abnormal dentin mineralization. Early and correct diagnosis of dentinogenesis imperfecta is imperative to enable appropriate preventive interventions and optimal dental treatment. Although pulpal pathosis is rarely reported with dentinogenesis imperfecta, endodontic treatment is occasionally necessary and has a guarded prognosis if initiated after pulp canal obliteration has occurred.

  2. AMELOGENESIS IMPERFECTA: A CLINICAL REPORT

    Directory of Open Access Journals (Sweden)

    Veena

    2015-01-01

    Full Text Available AIM: This clinical case report describes the oral rehabilitation of a young adult female patient diagnosed with hypoplastic Amelogenesis imperfecta. SUMMARY : Amelogenesis Imperfecta is a hereditary condition that affects the formation of the enamel mineralization process of both the primary and secondary dentition. It is clinically and genetically heterogeneous grou p of condition that affects both the quantity and quality of the enamel structure resulting in extensive loss of tooth tissue , poor esthetics and tooth sensitivity. The main objective for the selected treatment was to enhance the esthetics , and restoring m asticatory function. Treatment was divided into phases which included removal of impacted canine , lengthening of the maxillary and mandibular clinical crowns , and placement of anterior and posterior crowns.

  3. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia

    Directory of Open Access Journals (Sweden)

    MacKie Iain

    2008-11-01

    Full Text Available Abstract The hereditary dentine disorders, dentinogenesis imperfecta (DGI and dentine dysplasia (DD, comprise a group of autosomal dominant genetic conditions characterised by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000, whereas that of DD type 1 is 1 in 100,000. Clinically, the teeth are discoloured and show structural defects such as bulbous crowns and small pulp chambers radiographically. The underlying defect of mineralisation often results in shearing of the overlying enamel leaving exposed weakened dentine which is prone to wear. Currently, three sub-types of DGI and two sub-types of DD are recognised but this categorisation may change when other causative mutations are found. DGI type I is inherited with osteogenesis imperfecta and recent genetic studies have shown that mutations in the genes encoding collagen type 1, COL1A1 and COL1A2, underlie this condition. All other forms of DGI and DD, except DD-1, appear to result from mutations in the gene encoding dentine sialophosphoprotein (DSPP, suggesting that these conditions are allelic. Diagnosis is based on family history, pedigree construction and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Differential diagnoses include hypocalcified forms of amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann's disease, cyclic neutropenia, Chediak-Hegashi syndrome, histiocytosis X, Papillon-Lefevre syndrome, permanent teeth discolouration due to tetracyclines, Vitamin D-dependent and vitamin D-resistant rickets. Treatment involves removal of sources of infection or pain, improvement of aesthetics and protection of the posterior teeth from wear. Beginning in infancy, treatment usually continues into adulthood with a

  4. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia.

    Science.gov (United States)

    Barron, Martin J; McDonnell, Sinead T; Mackie, Iain; Dixon, Michael J

    2008-11-20

    The hereditary dentine disorders, dentinogenesis imperfecta (DGI) and dentine dysplasia (DD), comprise a group of autosomal dominant genetic conditions characterised by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000, whereas that of DD type 1 is 1 in 100,000. Clinically, the teeth are discoloured and show structural defects such as bulbous crowns and small pulp chambers radiographically. The underlying defect of mineralisation often results in shearing of the overlying enamel leaving exposed weakened dentine which is prone to wear. Currently, three sub-types of DGI and two sub-types of DD are recognised but this categorisation may change when other causative mutations are found. DGI type I is inherited with osteogenesis imperfecta and recent genetic studies have shown that mutations in the genes encoding collagen type 1, COL1A1 and COL1A2, underlie this condition. All other forms of DGI and DD, except DD-1, appear to result from mutations in the gene encoding dentine sialophosphoprotein (DSPP), suggesting that these conditions are allelic. Diagnosis is based on family history, pedigree construction and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Differential diagnoses include hypocalcified forms of amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann's disease, cyclic neutropenia, Chediak-Hegashi syndrome, histiocytosis X, Papillon-Lefevre syndrome), permanent teeth discolouration due to tetracyclines, Vitamin D-dependent and vitamin D-resistant rickets. Treatment involves removal of sources of infection or pain, improvement of aesthetics and protection of the posterior teeth from wear. Beginning in infancy, treatment usually continues into adulthood with a number of options including

  5. A study of dentinogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Eui Whan [Dept. of Oral Radiology, College of Dentistry, Chosun University, Kwangju (Korea, Republic of)

    1992-08-15

    The author observed a case of dentinogenesis imperfecta in a 8-year-old and a 9-year old brother with complaints of abnormal morphologic changes of the teeth. 1. Clinically, yellowish brown colored teeth, fractured crown and numerous retained root tips of edciduous teeth with severe attrition were observed in the both deciduous and permanent dentitions. 2. Radiographically, small-sized teeth partial or complete obliteration of the pulp chambers and pulp canals in the anterior teeth, partial obliteration of the pulp chambers and thin enamel in the permanent tooth germs were observed. 3. The familial history was their father has been lose his teeth early.

  6. Craniofacial distraction osteogenesis.

    Science.gov (United States)

    Winters, Ryan; Tatum, Sherard A

    2014-11-01

    Distraction osteogenesis (DO) may be the most versatile tool to become available to the craniofacial surgeon in recent years. It can be used in an ever-expanding register of clinical scenarios and offers major advantages over conventional craniofacial techniques in some circumstances. Craniofacial surgery has significant complications, some of which can be mitigated but not eliminated by choosing DO over conventional approaches. Although some DO applications are in their infancy with limited data, this article provides an overview of current uses of this versatile technology.

  7. Combined Treatment with Laser Sintering and Zirconium: A Case Report of Dentinogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Simel Ayyildiz

    2013-01-01

    Full Text Available Osteogenesis imperfecta (OI is a heterogeneous disorder of connective tissue that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis imperfecta (DI is sometimes an accompanying symptom of OI. The treatment protocol of these patients varies according to the clinical appearance. The case report here describes complete mouth rehabilitation of an 18-year-old male patient with OI and DI using direct metal laser sintering (DMLS technique of metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive metal fabrication technology that is simpler, more precise, and healthier than conventional manufacturing and can be remarkably cost effective. Moreover, the technique affords highly accurate production of fixed partial dentures with ideal marginal fit and excellent mechanical properties. The patient was treated using a multidisciplinary strategy that focused on controlling caries, protecting teeth from further wear, obtaining an appropriate vertical dimension, and providing soft tissue support to return the facial profile to a normal appearance using new technology in the field of prosthetics.

  8. Combined treatment with laser sintering and zirconium: a case report of dentinogenesis imperfecta.

    Science.gov (United States)

    Ayyildiz, Simel; Sahin, Cem; Akgün, Ozlem Marti; Basak, Feridun

    2013-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous disorder of connective tissue that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis imperfecta (DI) is sometimes an accompanying symptom of OI. The treatment protocol of these patients varies according to the clinical appearance. The case report here describes complete mouth rehabilitation of an 18-year-old male patient with OI and DI using direct metal laser sintering (DMLS) technique of metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive metal fabrication technology that is simpler, more precise, and healthier than conventional manufacturing and can be remarkably cost effective. Moreover, the technique affords highly accurate production of fixed partial dentures with ideal marginal fit and excellent mechanical properties. The patient was treated using a multidisciplinary strategy that focused on controlling caries, protecting teeth from further wear, obtaining an appropriate vertical dimension, and providing soft tissue support to return the facial profile to a normal appearance using new technology in the field of prosthetics.

  9. Dentinogenesis imperfecta: the importance of early treatment.

    Science.gov (United States)

    Delgado, Antonio Carlos; Ruiz, Matilde; Alarcón, Jose Antonio; González, Encarnación

    2008-03-01

    Dentinogenesis imperfecta, also known as hereditary opalescent dentin, is a dentin development disorder with autosomal dominant transmission that affects both the primary and permanent dentition. A case is reported of a family in which the mother and her 6- and 20-year-old children were diagnosed with dentinogenesis imperfecta type II. The mouths of these patients illustrate the progressive deterioration of affected teeth if not adequately treated. The treatment of the 6-year-old son is described, and therapeutic approaches to this disorder in primary and permanent dentition are reviewed. This family exemplifies the need for the earliest possible diagnosis and treatment of dentinogenesis imperfecta to prevent extensive deterioration of the dentition and occlusion.

  10. Distraction Osteogenesis Update: Introduction of Multidirectional Cranial Distraction Osteogenesis.

    Science.gov (United States)

    Gomi, Akira; Sunaga, Ataru; Kamochi, Hideaki; Oguma, Hirofumi; Sugawara, Yasushi

    2016-05-01

    In this review, we discuss in detail our current procedure for treating craniosynostosis using multidirectional cranial distraction osteogenesis (MCDO). The MCDO method allows all phenotypes of skull deformity to be reshaped by distraction osteogenesis, except in patients who are 5 months of age or younger and patients with posterior cranial vault problems. We report the results of clinical data of 36 children with craniosynostosis who underwent MCDO between 2005 and 2014 in our institute. This method has the following benefits, such as a high flexibility of reshaping, shorter treatment period and less invasive secondary intervention. We also discuss the other distraction osteogenesis techniques that are used to treat craniosynostosis and compare them with MCDO. The preferred procedure for correction of craniosynostosis may depend on the patient's age, the extent of deformity, and the extent of correction achievable by surgery. We can arrange the combinations of various methods according to the advantage and disadvantage of each technique.

  11. Enamel formation and amelogenesis imperfecta.

    Science.gov (United States)

    Hu, Jan C-C; Chun, Yong-Hee P; Al Hazzazzi, Turki; Simmer, James P

    2007-01-01

    Dental enamel is the epithelial-derived hard tissue covering the crowns of teeth. It is the most highly mineralized and hardest tissue in the body. Dental enamel is acellular and has no physiological means of repair outside of the protective and remineralization potential provided by saliva. Enamel is comprised of highly organized hydroxyapatite crystals that form in a defined extracellular space, the contents of which are supplied and regulated by ameloblasts. The entire process is under genetic instruction. The genetic control of amelogenesis is poorly understood, but requires the activities of multiple components that are uniquely important for dental enamel formation. Amelogenesis imperfecta (AI) is a collective designation for the variety of inherited conditions displaying isolated enamel malformations, but the designation is also used to indicate the presence of an enamel phenotype in syndromes. Recently, genetic studies have demonstrated the importance of genes encoding enamel matrix proteins in the etiology of isolated AI. Here we review the essential elements of dental enamel formation and the results of genetic analyses that have identified disease-causing mutations in genes encoding enamel matrix proteins. In addition, we provide a fresh perspective on the roles matrix proteins play in catalyzing the biomineralization of dental enamel.

  12. Multiple Unerupted Teeth with Amelogenesis Imperfecta in Siblings

    Directory of Open Access Journals (Sweden)

    Shruthi Hegde

    2012-01-01

    Full Text Available Amelogenesis imperfecta encompasses a group of inherited abnormalities that are generally considered to primarily affect the formation and/or calcification of enamel. This case report describes the unusual presentation of amelogenesis imperfecta in siblings as multiple unerupted teeth, multiple pulpal calcifications, and multiple dilacerations of roots along with the defect in the enamel. The intent of our report is to highlight a rare co-occurrence of amelogenesis imperfecta with multiple morphologic alterations in siblings.

  13. Multiple unerupted teeth with amelogenesis imperfecta in siblings.

    Science.gov (United States)

    Hegde, Shruthi

    2012-05-01

    Amelogenesis imperfecta encompasses a group of inherited abnormalities that are generally considered to primarily affect the formation and/or calcification of enamel. This case report describes the unusual presentation of amelogenesis imperfecta in siblings as multiple unerupted teeth, multiple pulpal calcifications, and multiple dilacerations of roots along with the defect in the enamel. The intent of our report is to highlight a rare co-occurrence of amelogenesis imperfecta with multiple morphologic alterations in siblings.

  14. Study on the Pathogenic Gene of Dentinogenesis Imperfecta of Type Ⅱ%Ⅱ型牙本质发育不全的致病基因研究进展

    Institute of Scientific and Technical Information of China (English)

    吴柒柱; 吉日木图; 齐玥; 陈宇杰; 刘海平; 白海花

    2009-01-01

    牙本质发育不全症是一种常染色体显性遗传病,其致病基因定位于4q2l.临床上分为三型:Ⅰ型(Dentinogenesis Imperfecta type Ⅰ, DGI-Ⅰ) 主要见于成骨发育不全(Osteogenesis Imperfecta, OI)患者的口腔,其病因被广泛认为是由Ⅰ型胶原基因突变导致.Ⅲ型(Dentinogenesis Imperfecta type Ⅲ, DGI-Ⅲ)是一种特殊的遗传性牙本质发育不全,在美国马里兰州的3个隔离民族群中独立发生.Ⅱ型(Dentinogenesis Imperfecta typeⅡ, DGI-Ⅱ)在临床上最为常见,成为研究热点.Ⅱ型牙本质发育不全的致病基因主要为牙本质唾液酸焦磷酸蛋白基因(dentin sialophosphoprotein, DSPP)突变引起,独立发生且具有高度的遗传异质性.主要对牙本质发育不全Ⅱ型的候选基因及DSPP的突变进行了综述.

  15. Amelogenesis imperfecta and localised aggressive periodontitis: A rare clinical entity

    Directory of Open Access Journals (Sweden)

    Gayatri Gundannavar

    2013-01-01

    Full Text Available This case report presents two female patients whose chief complaint was discoloration of teeth. On careful clinical examination it was found that the patients had features of amelogenesis imperfecta and localised aggressive periodontitis. This article will give an insight of clinical and radiographic features of amelogenesis imperfecta with localised aggressive periodontitis, which is a rare clinical entity.

  16. [Distraction osteogenesis: principles, history and background

    NARCIS (Netherlands)

    Vissink, A.; Baat, C. de

    2008-01-01

    Distraction osteogenesis is a treatment in which new bone is created in the space which comes to exist between bone fragments that have slowly been driven apart by osteogenesis. This treatment, originally developed in orthopaedic surgery, is also commonly used for correcting deformities in the head

  17. Alveolar distraction osteogenesis – Crestal widening by distraction osteogenesis

    Directory of Open Access Journals (Sweden)

    Zvi Laster

    2010-04-01

    Full Text Available Following tooth extraction, resorption of the residual ridges occurs in both the vertical and the horizontal directions. Most of this resorption occurs within the first 6 months after tooth extraction. To correc tthis vertical/ horizontal/ dual situation, several surgical approaches have been proposed: autogenous bone grafts, guided bone regeneration, and alveolar distraction osteogenesis (ADO. In recent years, ADO has gained an ongoing popularity ,especially in view of its numerous advantages, mostimportant among them being the shortening of treatment periods and earlier dental implant placement. In cases in which there is sufficient vertical height but not enough bucco-ligual width to accommodate an implant, crestal width has to be built. Crestal widening by distraction osteogenesis is the preferred technique in suchcases. In this study a new type of crest widener, the"Laster" Crest Widening Distractor, is presented, reporting two cases where crest widening by distraction was chosen as the preferred treatment plan. Finally the main advantages and disadvantages of the new crest widening distractor are discussed, helping thus the clinician to make up his mind about this new promising device and surgical technique.

  18. Amelogenesis imperfecta: review of diagnostic findings and treatment concepts.

    Science.gov (United States)

    Sabandal, Martin M I; Schäfer, Edgar

    2016-09-01

    Mineralization defects like amelogenesis imperfecta are often of hereditary origin. This article reviews the diagnostic findings and summarizes the suggested treatment approaches. Currently, there are no defined therapy recommendations available for patients suffering from amelogenesis imperfecta. The mentioned therapies are more or less equal but no comprehensive therapy recommendation is evident. When treating patients suffering from amelogenesis imperfecta, a comprehensive therapy of almost every dental discipline has to be considered. The earlier the diagnosis of amelogenesis imperfecta is confirmed, the better the outcome is. Optimal treatment approaches consist of early diagnosis and treatment approach and frequent dental recall appointments to prevent progressive occlusal wear or early destruction by caries. Full-mouth prosthetic treatment seems to be the best treatment option. PMID:27550338

  19. Amelogenesis imperfecta: review of diagnostic findings and treatment concepts.

    Science.gov (United States)

    Sabandal, Martin M I; Schäfer, Edgar

    2016-09-01

    Mineralization defects like amelogenesis imperfecta are often of hereditary origin. This article reviews the diagnostic findings and summarizes the suggested treatment approaches. Currently, there are no defined therapy recommendations available for patients suffering from amelogenesis imperfecta. The mentioned therapies are more or less equal but no comprehensive therapy recommendation is evident. When treating patients suffering from amelogenesis imperfecta, a comprehensive therapy of almost every dental discipline has to be considered. The earlier the diagnosis of amelogenesis imperfecta is confirmed, the better the outcome is. Optimal treatment approaches consist of early diagnosis and treatment approach and frequent dental recall appointments to prevent progressive occlusal wear or early destruction by caries. Full-mouth prosthetic treatment seems to be the best treatment option.

  20. Amelogenesis Imperfecta with Coronal Resorption: Report of Three Cases.

    Science.gov (United States)

    Bhatia, Shannu K; Hunter, M Lindsay; Ashley, Paul F

    2015-12-01

    Intracoronal resorption of the permanent dentition in cases of amelogenesis imperfecta (AI) is a rare finding which poses an added complication to the already complex management of this condition. This paper presents three cases of AI associated with delayed eruption of permanent teeth in which asymptomatic intracoronal resorption occurred. CPD/Clinical Relevance: This paper highlights the fact that teeth affected with amelogenesis imperfecta may undergo asymptomatic intracoronal resorption which is only identifiable radiographically.

  1. Interradicular dentin dysplasia associated with amelogenesis imperfecta with taurodontism or trichodentoosseous syndrome: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Veda Hegde

    2014-01-01

    Full Text Available Amelogenesis imperfecta is a hereditary disorder with diverse clinical presentation, where enamel is the tissue that is primarily affected either quantitatively or qualitatively. Hypomaturation/hypoplastic amelogenesis imperfecta with taurodontism is a rare variant of amelogenesis imperfecta which is often confused with trichodentoosseous syndrome. We report a rare case of hereditary enamel defect with taurodontism associated with interradicular dentin dysplasia.

  2. Interradicular dentin dysplasia associated with amelogenesis imperfecta with taurodontism or trichodentoosseous syndrome: a diagnostic dilemma.

    Science.gov (United States)

    Hegde, Veda; Srikanth, K

    2014-01-01

    Amelogenesis imperfecta is a hereditary disorder with diverse clinical presentation, where enamel is the tissue that is primarily affected either quantitatively or qualitatively. Hypomaturation/hypoplastic amelogenesis imperfecta with taurodontism is a rare variant of amelogenesis imperfecta which is often confused with trichodentoosseous syndrome. We report a rare case of hereditary enamel defect with taurodontism associated with interradicular dentin dysplasia.

  3. Transcriptional repression of the Dspp gene leads to dentinogenesis imperfecta phenotype in Col1a1-Trps1 transgenic mice.

    Science.gov (United States)

    Napierala, Dobrawa; Sun, Yao; Maciejewska, Izabela; Bertin, Terry K; Dawson, Brian; D'Souza, Rena; Qin, Chunlin; Lee, Brendan

    2012-08-01

    Dentinogenesis imperfecta (DGI) is a hereditary defect of dentin, a calcified tissue that is the most abundant component of teeth. Most commonly, DGI is manifested as a part of osteogenesis imperfecta (OI) or the phenotype is restricted to dental findings only. In the latter case, DGI is caused by mutations in the DSPP gene, which codes for dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Although these two proteins together constitute the majority of noncollagenous proteins of the dentin, little is known about their transcriptional regulation. Here we demonstrate that mice overexpressing the Trps1 transcription factor (Col1a1-Trps1 mice) in dentin-producing cells, odontoblasts, present with severe defects of dentin formation that resemble DGI. Combined micro-computed tomography (µCT) and histological analyses revealed tooth fragility due to severe hypomineralization of dentin and a diminished dentin layer with irregular mineralization in Col1a1-Trps1 mice. Biochemical analyses of noncollagenous dentin matrix proteins demonstrated decreased levels of both DSP and DPP proteins in Col1a1-Trps1 mice. On the molecular level, we demonstrated that sustained high levels of Trps1 in odontoblasts lead to dramatic decrease of Dspp expression as a result of direct inhibition of the Dspp promoter by Trps1. During tooth development Trps1 is highly expressed in preodontoblasts, but in mature odontoblasts secreting matrix its expression significantly decreases, which suggests a Trps1 role in odontoblast development. In these studies we identified Trps1 as a potent inhibitor of Dspp expression and the subsequent mineralization of dentin. Thus, we provide novel insights into mechanisms of transcriptional dysregulation that leads to DGI.

  4. El poder en la paz imperfecta y en Foucault

    Directory of Open Access Journals (Sweden)

    Cássia M. Rosato

    2012-04-01

    Full Text Available Este trabajo debate el concepto de poder en la paz imperfecta y en la obra de Foucault. El objetivo principal es demostrar que la perspectiva foucaultiana del poder no está lejos de la noción de poder en la paz imperfecta propuesta por Muñoz. Para tanto, ese artículo empieza con la idea de paz de UNESCO y el contexto sociopolítico que favoreció el surgimiento de esa concepción. Enseguida, presenta características de la paz imperfecta, así como el concepto de poder está inserido en esta proposición y en Foucault. Al final, apunta tres semejanzas y/o aproximaciones existentes entre ambas las orientaciones que confirman su cercanía.

  5. Interdisciplinary approach to oral rehabilitation of patient with amelogenesis imperfecta.

    Science.gov (United States)

    Yilmaz, Burak; Oz, Ulas; Yilmaz, Hasan Guney

    2014-03-01

    Amelogenesis imperfecta is a hereditary condition that affects the development of enamel, causing quantity, structural and compositional anomalies that involve all dentitions. Consequently, the effects can extend to both the primary and secondary dentitions. Patients with amelogenesis imperfecta may present with clinical difficulties, such as insufficient crown length, tooth sensitivity and orthodontic discrepancies, all of which can be resolved successfully with an interdisciplinary approach. This case report describes the interdisciplinary approach to the treatment of a 22-year-old patient with amelogenesis imperfecta. The proper alignment of anterior teeth and gingivo-cervical line was provided with orthodontic and periodontal treatments. All-ceramic crowns were placed on anterior, and metal-ceramic restorations were placed on posterior teeth to reduce sensitivity and improve esthetics with function. Improved esthetic appearance, reduced tooth sensitivity and the resolution of a potentially harmful psychosocial condition were achieved. Patient remained satisfied in the 12-month follow-up examination.

  6. Dentinogenesis imperfecta: long-term rehabilitation in a child.

    Science.gov (United States)

    Bouvier, Dominique; Leheis, Benoît; Duprez, Jean-Pierre; Bittar, Elias; Coudert, Jean-Loup

    2008-01-01

    The treatment of dentinogenesis imperfecta represents a challenge for the dental practitioner. The aim of this case report was to describe the chronology and problems encountered in the long-term rehabilitation of a young girl suffering from dentinogenesis imperfecta with severe attrition. A 2-stage treatment over a period of 9 years is described and discussed. This treatment comprised an initial treatment to restore esthetic appearance and function during primary and mixed dentitions and a complete prosthetic rehabilitation in a second stage to protect permanent teeth with low-fusion ceramicmetal individual crowns. Discovery of a follicular cyst is also reported and its treatment is described.

  7. Amelogenesis imperfecta and the treatment plan - interdisciplinary team approach.

    Science.gov (United States)

    Suchancova, B; Holly, D; Janska, M; Stebel, J; Lysy, J; Thurzo, A; Sasinek, S

    2014-01-01

    Amelogenesis imperfecta is a set of hereditary defects representing mainly the development defects of enamel without the presence of whole-body symptoms. Developmental disorders can manifest a complete absence of enamel, which is caused by improper differentiation of ameloblasts. This article describes the diagnosis and treatment of a patient with amelogenesis imperfecta, as well as the need for interdisciplinary cooperation to achieve the best possible morphological, skeletal, functional and aesthetic rehabilitation of the patients with this diagnosis. Furthermore, the article reviews literature dealing with other anomalies occurring in association with amelogenesis imperfect (Fig. 12, Ref. 20).

  8. Dentinogenesis imperfecta: an early treatment strategy.

    Science.gov (United States)

    Sapir, S; Shapira, J

    2001-01-01

    Dentinogenesis imperfecta (DI) type 2 is a disease inherited in a simple autosomal dominant mode. As soon as the teeth erupt the parents may notice the problem and look for a pediatric dentist's advice and treatment. Early diagnosis and treatment of DI is recommended, as it may prevent or intercept deterioration of the teeth and occlusion and improve esthetics. The purpose of this article is to present the objectives, treatment options, and problems encountered in the treatment of DI in the early primary dentition. A two-stage treatment of a toddler under general anesthesia is described and discussed. This paper recommends for severe cases of DI two treatment stages performed under general anesthesia. Stage 1 is early (around age 18-20 months) and is directed to covering the incisors with composite restorations and the first primary molars with preformed crowns. Stage 2 (around age 28-30 months) seeks to protect the second primary molars with preformed crowns and cover the canines with composite restorations.

  9. Distraction osteogenesis using a longitudinal corticotomy

    OpenAIRE

    AL-SAATI, Ma'ad F.; Magnussen, Robert A; LUSTIG, Sebastien; Testa, Rodolphe; Al-Saati, Gazal; Al-Saati, Faisal

    2011-01-01

    The purpose of this study was to evaluate whether the use of a longitudinal corticotomy (S-Z osteotomy) results in more rapid consolidation following distraction osteogenesis of short tibiae. Sixty-seven lengthening procedures were performed in 51 patients ranging in age from nine to 38 (mean 25) years.

  10. A Case of Dentinogenesis Imperfecta Treated with Submerged Root Technique.

    Science.gov (United States)

    Uday, Ginjupally; Chandar, Bhanu; Srilakshmi, J; Khaitan, Tanya; Babu, B Balaji

    2015-09-01

    Dentinogenesis imperfecta (DGI), an autosomal dominant trait, is one of the most common hereditary disorders affecting both the formation and mineralization of dentin. Either or both primary and permanent dentition is affected by it. Here, we present a case report of a 13-year-old female patient affected with DGI who had undergone prosthetic rehabilitation with submerged root technique.

  11. Amelogenesis imperfecta and anterior open bite: Etiological, classification, clinical and management interrelationships.

    Science.gov (United States)

    Alachioti, Xanthippi Sofia; Dimopoulou, Eleni; Vlasakidou, Anatoli; Athanasiou, Athanasios E

    2014-01-01

    Although amelogenesis imperfecta is not a common dental pathological condition, its etiological, classification, clinical and management aspects have been addressed extensively in the scientific literature. Of special clinical consideration is the frequent co-existence of amelogenesis imperfecta with the anterior open bite. This paper provides an updated review on amelogenesis imperfecta as well as anterior open bite, in general, and documents the association of these two separate entities, in particular. Diagnosis and treatment of amelogenesis imperfecta patients presenting also with anterior open bite require a lengthy, comprehensive and multidisciplinary approach, which should aim to successfully address all dental, occlusal, developmental, skeletal and soft tissue problems associated with these two serious clinical conditions.

  12. Characterization of the nanoscratch, microstructure, and composition in hypoplastic amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Ping Qing

    2015-07-01

    Full Text Available Hypoplastic amelogenesis imperfecta is a widespread hereditary disease that causes the loss of enamel. The purpose of this study was to investigate the nanoscratch resistance of hypoplastic amelogenesis imperfecta for providing a reference for restorative treatment. Four unerupted third molars from a patient diagnosed with hypoplastic amelogenesis imperfecta and seven unerupted third molars from normal individuals were compared. Atomic force microscopy and energy-dispersive X-ray spectroscopy were used to observe the microstructure and composition of the teeth (enamel and dentin. The nanoscratch tests of teeth (enamel and dentin were investigated using a nanoscratch tester, scanning electron microscopy, and a stylus profilometer. The results indicated that hypoplastic amelogenesis imperfecta teeth had different microstructures compared to normal teeth. Hypoplastic amelogenesis imperfecta demonstrated a higher composition of organic substance. Meanwhile, the friction coefficient of hypoplastic amelogenesis imperfecta was higher than that of normal teeth, and inferior frictional resistance of hypoplastic amelogenesis imperfecta teeth was observed. The main damaging mechanisms observed in hypoplastic amelogenesis imperfecta under nanoscratch were the combination of delamination, debris, and cracks in enamel with delamination, debris, and plastic deformation in dentin. Our findings suggested that new dental restorative materials should be selected to match the mechanical properties of hypoplastic amelogenesis imperfecta.

  13. Cytotoxic agents are detrimental to bone formed by distraction osteogenesis

    OpenAIRE

    Monsell, Fergal P.; Barnes, James Ralph; Bellemore, M. C.; Biston, L.; Goodship, Allen

    2013-01-01

    Distraction osteogenesis can be used to replace segmental bone loss when treating malignant bone tumors in children and adolescents. These patients often receive cytotoxic chemotherapy as part of their treatment regimen. The effect of cytotoxic drugs on the cellular processes during distraction osteogenesis and the structural and mechanical properties of regenerate bone is unknown. We therefore used a rabbit model of distraction osteogenesis to determine that cytotoxic agents had a detrimenta...

  14. Distraction osteogenesis in a severe mandibular deficiency

    Directory of Open Access Journals (Sweden)

    Ozyigit Aykut H

    2007-01-01

    Full Text Available Abstract Objective Distraction osteogenesis is an alternative treatment method for the correction of mandibular hypoplasia. In this case report, distraction with a multidirectional extraoral device was performed to gradually lengthen the corpus and ramus of a patient who had a severe hypoplastic mandible. Materials and methods The patient underwent bilateral extraoral ramus and corpus distraction osteogenesis. After seven days of latency period, distraction was performed 0.5 mm twice a day. Subsequent consolidation period was 12 weeks. Results The patient's mandible was elongated successfully. Cephalometric analysis revealed that ANB angle decreased from 13° to 6°, overjet of 15 mm decreased to 4 mm, corpus length increased from 49 mm to 67 mm, and ramus length increased from 41 mm to 43 mm. Posterior airway space (PAS also increased due to advancement of the mandible. In stereolithographic model evaluation it was determined that the distances from condylion to gonion and from gonion to pogonion increased. Conclusion Satisfactory results from both aesthetic and functional standpoints were obtained by distraction osteogenesis of the ramus and corpus.

  15. Isolated dentinogenesis imperfecta and dentin dysplasia: revision of the classification.

    Science.gov (United States)

    de La Dure-Molla, Muriel; Philippe Fournier, Benjamin; Berdal, Ariane

    2015-04-01

    Dentinogenesis imperfecta is an autosomal dominant disease characterized by severe hypomineralization of dentin and altered dentin structure. Dentin extra cellular matrix is composed of 90% of collagen type I and 10% of non-collagenous proteins among which dentin sialoprotein (DSP), dentin glycoprotein (DGP) and dentin phosphoprotein (DPP) are crucial in dentinogenesis. These proteins are encoded by a single gene: dentin sialophosphoprotein (DSPP) and undergo several post-translational modifications such as glycosylation and phosphorylation to contribute and to control mineralization. Human mutations of this DSPP gene are responsible for three isolated dentinal diseases classified by Shield in 1973: type II and III dentinogenesis imperfecta and type II dentin dysplasia. Shield classification was based on clinical phenotypes observed in patient. Genetics results show now that these three diseases are a severity variation of the same pathology. So this review aims to revise and to propose a new classification of the isolated forms of DI to simplify diagnosis for practitioners.

  16. Homozygous and compound heterozygous MMP20 mutations in amelogenesis imperfecta.

    Science.gov (United States)

    Gasse, B; Karayigit, E; Mathieu, E; Jung, S; Garret, A; Huckert, M; Morkmued, S; Schneider, C; Vidal, L; Hemmerlé, J; Sire, J-Y; Bloch-Zupan, A

    2013-07-01

    In this article, we focus on hypomaturation autosomal-recessive-type amelogenesis imperfecta (type IIA2) and describe 2 new causal Matrix metalloproteinase 20 (MMP20) mutations validated in two unrelated families: a missense mutation p.T130I at the expected homozygous state, and a compound heterozygous mutation having the same mutation combined with a nucleotide deletion, leading to a premature stop codon (p.N120fz*2). We characterized the enamel structure of the latter case using scanning electron microscopy analysis and microanalysis (Energy-dispersive X-ray Spectroscopy, EDX) and confirmed the hypomaturation-type amelogenesis imperfecta as identified in the clinical diagnosis. The mineralized content was slightly decreased, with magnesium substituting for calcium in the crystal structure. The anomalies affected enamel with minimal inter-rod enamel present and apatite crystals perpendicular to the enamel prisms, suggesting a possible new role for MMP20 in enamel formation.

  17. Multidisciplinary approach for a patient with dentinogenesis imperfecta and anterior trauma.

    Science.gov (United States)

    Roh, Won-Jong; Kang, Seung-Goo; Kim, Su-Jung

    2010-09-01

    Dentinogenesis imperfecta is an inherited dentinal dysplasia involving several risks for orthodontic treatment. This case report describes the multidisciplinary treatment of a 17-year-old girl whose Class II Division 1 malocclusion was complicated by dentinogenesis imperfecta type II and maxillary anterior trauma.

  18. All-ceramic restorations for complete-mouth rehabilitation in dentinogenesis imperfecta: a case report.

    Science.gov (United States)

    Moundouri-Andritsakis, Heleni; Kourtis, Stephanos G; Andritsakis, Demetrios P

    2002-10-01

    Prosthetic treatment of patients with dentinogenesis imperfecta is a challenge for the dental practitioner because numerous factors have to be considered. The use of all-ceramic restorations to rehabilitate the dentition of a young patient with dentinogenesis imperfecta is reported. Clinical and laboratory procedures are described.

  19. Early restorative rehabilitation of children and adolescents with amelogenesis imperfecta

    OpenAIRE

    Pousette Lundgren, Gunilla

    2015-01-01

    Amelogenesis imperfecta (AI) is a rare, genetically determined defect in enamel mineralization. Patients with (AI) can present with rapid tooth loss or fractures of enamel and dental sensitivity as well as alterations in enamel thickness, color, and shape. These factors may compromise esthetic appearance and masticatory function. Existing treatment recommendations suggest using resin composite restorations until adulthood, although such restorations have a limited longevity. The mai...

  20. Identification of gene mutation in patients with osteogenesis imperfect using high resolution melting analysis.

    Science.gov (United States)

    Wang, Jianhai; Ren, Xiuzhi; Bai, Xue; Zhang, Tianke; Wang, Yi; Li, Keqiu; Li, Guang

    2015-01-01

    Osteogenesis imperfecta (OI), a congenital bone disorder, is caused by mutations in COL1A1 and COL1A2 genes, leading to deficiency of type I collagen. The high resolution melting (HRM) analysis has been used for detecting mutations, polymorphisms and epigenetic alteration in double-stranded DNAs. This study was to evaluate the potential application of HRM analysis for identifying gene mutations in patients with OI. This study included four children with OI and their parents and fifty normal people as controls. Blood samples were collected for HRM analysis of PCR-amplified exons and flanking DNA sequences of COL1A1 and COL1A2 genes. Direct gene sequencing was performed to validate HRM-identified gene mutations. As compared to controls, HRM analysis of samples form children with OI showed abnormal melting curves in exons 11 and 33-34 of the COL1A1 gene and exons 19 and 48 of the COL1A2 gene, which indicates the presence of heterozygous mutations in COL1A1 and COL1A2 genes. In addition to two known mutations in the COL1A2 gene, c.982G > A and c.3197G > T, sequencing analysis identified two novel mutations in the COL1A1 gene, c.2321delC and c.768dupC mutations, which function as premature stop codons. These results support future studies of applying HRM analysis as a diagnostic approach for OI. PMID:26307460

  1. Maxillary Tuberosity Reconstruction with Transport Distraction Osteogenesis

    OpenAIRE

    F. Ugurlu; Basel, B.; B. Cem Sener; A. Sertgöz

    2012-01-01

    Severe bone loss due to pathology in the maxillary tuberosity region is a challenging problem both surgically and prosthetically. Large bone grafts have a poor survival rate due to the delicate bony architecture in this area and presence of the maxillary sinus. Our case presentation describes a new technique for reconstructing severe bony defect in the maxillary tuberosity with horizontal distraction osteogenesis in a 45-year-old man. A 4 × 6 × 3 cm cyst was discovered in the left maxillary m...

  2. Distraction osteogenesis with pivot plate in the treatment of scaphocephaly.

    Science.gov (United States)

    Nam, Seung Min; Kim, Yong Bae; Shin, Ho Seong; Park, Eun Soo; Jung, Sung Gyun

    2011-01-01

    In scaphocephaly, traditional distraction osteogenesis increases only the bitemporal width. We describe distraction osteogenesis with a pivot plate for scaphocephaly, which not only increases the bitemporal width but also decreases the anteroposterior length. Three patients with scaphocephaly were treated using distraction osteogenesis with a pivot plate between January 2005 and June 2006. These children underwent cranial reshaping by gradual distraction using an external distraction device and pivot plate. The distraction rate was 1 mm/d, and the latency period was 5 days. The follow-up period after distraction osteogenesis ranged from 16 to 24 months. No specific complications, such as accidental removal of the distraction devices, infection, or neurologic problems in any patient, occurred. The mean distraction was 45 mm. The mean cranial index was 73.6. Distraction osteogenesis for scaphocephaly is still in the development stage, but it is becoming accepted as a useful method because of its many advantages. Distraction osteogenesis with a pivot plate for scaphocephaly is better than other distraction osteogenesis techniques because it induces increased bitemporal width and decreased anteroposterior length synchronously.

  3. Maxillary Tuberosity Reconstruction with Transport Distraction Osteogenesis

    Directory of Open Access Journals (Sweden)

    F. Ugurlu

    2012-01-01

    Full Text Available Severe bone loss due to pathology in the maxillary tuberosity region is a challenging problem both surgically and prosthetically. Large bone grafts have a poor survival rate due to the delicate bony architecture in this area and presence of the maxillary sinus. Our case presentation describes a new technique for reconstructing severe bony defect in the maxillary tuberosity with horizontal distraction osteogenesis in a 45-year-old man. A 4×6×3cm cyst was discovered in the left maxillary molar region and enucleated. Three months postoperatively, the area had a severe bone defect extending to the zygomatic buttress superiorly and hamular notch posteriorly. Three months later, a bone segment including the right upper second premolar was osteotomised and distracted horizontally. The bone segment was distracted 15 mm distally. After consolidation, implants were placed when the distractor was removed. A fixed denture was loaded over the implants after 3 months. Complete alveolar bone loss extending to the cranial base can be reconstructed with transport distraction osteogenesis. Distalisation of the alveolar bone segment adjacent to the bony defect is an easy method for reconstructing such severe defects.

  4. Spring-mediated mandibular distraction osteogenesis.

    Science.gov (United States)

    Mofid, Mehrdad M; Inoue, Nozomu; Tufaro, Anthony P; Vander Kolk, Craig A; Manson, Paul N

    2003-09-01

    Successful performance of distraction osteogenesis requires rigorous patient compliance with a daily activation regimen of a percutaneous screw. Previous clinical studies have found that failure of patient compliance with this regimen is the most common complication leading to technical failure of the distraction process. The authors have developed an internalized spring-mediated device for mandibular distraction osteogenesis that can potentially abrogate the risks associated with patient compliance by allowing for automated distraction across an osteotomy. Twenty adult New Zealand White rabbits underwent unilateral mandibular osteotomy. A segment of nickel-titanium shape memory alloy reinforced at both ends with a pinball was fashioned into an inferiorly based arc and secured to the mandible with stainless steel wire. On postoperative day 12, spring activation commenced by cutting a wire binding the two pinballs to one another. Animals were observed for 6 weeks before they were killed. Radiographic studies and decalcified histologic analysis were performed on extracted mandibles. Temperature- and displacement-dependent properties of the shape memory alloy were also examined. Five animals were excluded from the study due to infection, nonunion, or device failure. A mean distraction of 1.2 mm in the distracted hemimandible relative to the nonoperated hemimandible was found (P development of devices will incorporate technology that permits fully internalized and automated distraction to occur. PMID:14501343

  5. Management of Mandibular Hypoplasia Using Distraction Osteogenesis Technique

    Institute of Scientific and Technical Information of China (English)

    陶学金; 樊敏; 凌翔; 陈卫民

    2004-01-01

    Summary: By using distraction osteogenesis technique, 3 cases of mandibular hypoplasia were treated by home-made and German-made jaw distractors: including one patient suffered from bilateral ankylosis of temporo-mandibular joint and 2 patients from deficiency of mandible. The duration of distraction osteogenesis was one month. The bone distractor was removed 3 months after operation. Satisfactory results were obtained in all 3 cases. Distraction osteogenesis can successfully be used in mandibular functional reconstruction and has much more advantages than traditional technique.

  6. Crown lengthening procedure in the management of amelogenesis imperfecta.

    Science.gov (United States)

    Kalaivani, S; Manohar, Jenish; Shakunthala, P; Sujatha, S; Rajasekaran, S A; Karthikeyan, B; Kalaiselvan, S

    2015-08-01

    Full mouth rehabilitation includes a promising treatment planning and execution thus fulfilling esthetic, occlusal, and functional parameters maintaining the harmony of the stomatognathic system. Crown lengthening procedures have become an integral component of the esthetic armamentarium and are utilized with increasing frequency to enhance the appearance of restorations placed in the esthetic zone. Crown lengthening plays a role to create healthy relationship of the gingiva and bone levels so as to gain access to more of the tooth which can be restored, if it is badly worn, decayed or fractured, below the gum line. This paper highlights the full mouth crown lengthening procedure performed on a patient with amelogenesis imperfecta.

  7. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia

    OpenAIRE

    MacKie Iain; McDonnell Sinead T; Barron Martin J; Dixon Michael J

    2008-01-01

    Abstract The hereditary dentine disorders, dentinogenesis imperfecta (DGI) and dentine dysplasia (DD), comprise a group of autosomal dominant genetic conditions characterised by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000, whereas that of DD type 1 is 1 in 100,000. Clinically, the teeth are discoloured and show structural defects such as bulbous crowns and small pulp cham...

  8. Management of dentinogenesis imperfecta: a review of two case reports.

    Science.gov (United States)

    Rafeek, Reisha N; Paryag, Amit; Al-Bayaty, Haytham

    2013-01-01

    Dentinogenesis imperfecta (DI) is an inherited disorder that affects dentin and often manifests as tooth discoloration; in addition, the dentition is also extremely susceptible to wear. Treatment of DI focuses primarily on protecting affected dentin, reducing sensitivity, and improving esthetics. Routine restorative materials, such as amalgams and composites, may be used. In more severe cases, the treatment of choice is full coverage crowns, while bonding of veneers may be used to improve the esthetics of the anterior teeth. This study presents two cases of Type II DI in the same family and the management of each case. Restorative management included amalgams, composite veneers, crowns, bridges, and overdentures.

  9. Adhesive Restorations as An Esthetic Solution in Dentinogenesis Imperfecta.

    Science.gov (United States)

    Ubaldini, Adriana Lemos Mori; Giorgi, Maria Cecília Caldas; Carvalho, Ariany Borges; Pascon, Fernanda Miori; Lima, Débora Alves Nunes Leite; Baron, Gisele Maria Marchi; Paulillo, Luís Alexandre Maffei Sartini; Aguiar, Flávio Henrique Baggio

    2015-01-01

    Loss of tooth structure is the main sequela of dentinogenesis imperfecta (DI). Due to severe enamel attrition, patients with DI often present with esthetic, occlusal, endodontic, and speech complications. Therefore, an interdisciplinary approach, divided into separate clinical steps, should be developed to provide comprehensive dental rehabilitation. The purpose of this case report is to discuss the use of composite resin restorations as a transitional treatment step for the anterior teeth of an eight-year-old boy with DI until his bone and dental development permit orthodontic and orthognatic surgery.

  10. Dentinogenesis imperfecta type II: an affected family saga.

    Science.gov (United States)

    Kamboj, Mala; Chandra, Anil

    2007-09-01

    Dentinogenesis imperfecta (DI) type II or hereditary opalescent dentin is inherited in simple autosomal dominant mode with high penetrance and low mutation rate. It generally affects both the deciduous and permanent dentitions. DI type II corresponds to a localized form of mesodermal dysplasia, observed in histodifferentiation. Early diagnosis and treatment are therefore, fundamental, aiming at obtaining a favourable prognosis since late intervention makes treatment more complex. We present two cases of DI type II with the disease affecting three generations of a family in India, and briefly highlight the molecular basis of this disease.

  11. Crown lengthening procedure in the management of amelogenesis imperfecta

    Science.gov (United States)

    Kalaivani, S.; Manohar, Jenish; Shakunthala, P.; Sujatha, S.; Rajasekaran, S. A.; Karthikeyan, B.; Kalaiselvan, S.

    2015-01-01

    Full mouth rehabilitation includes a promising treatment planning and execution thus fulfilling esthetic, occlusal, and functional parameters maintaining the harmony of the stomatognathic system. Crown lengthening procedures have become an integral component of the esthetic armamentarium and are utilized with increasing frequency to enhance the appearance of restorations placed in the esthetic zone. Crown lengthening plays a role to create healthy relationship of the gingiva and bone levels so as to gain access to more of the tooth which can be restored, if it is badly worn, decayed or fractured, below the gum line. This paper highlights the full mouth crown lengthening procedure performed on a patient with amelogenesis imperfecta. PMID:26538965

  12. [Dentinogenesis imperfecta: a developmental anomaly of the dentin in the primary dentition. A literature review].

    Science.gov (United States)

    Bercovich, R

    2010-01-01

    This literature review summarizes the current knowledge about Dentinigenesis Imperfecta, a developmental anomaly of thedentin.The phenomenon's classification is presented in details, as well as its etiology, clinical, rentgenological and histological characteristics. In addition, the treatment modes are described.

  13. [Distraction osteogenesis of deficient alveolar bone prior to dental rehabilitation].

    Science.gov (United States)

    Shilo, D; Emodi, O; Aizenbud, D; Rachmiel, A

    2015-07-01

    Implant supported rehabilitation has become very common in treatment plans nowadays, yet many patients lack the vertical and horizontal bone dimensions required for endosseous implant insertion. Distraction osteogenesis is a technique in which bone is generated by progressive elongation of two bone fragments following an osteotomy or corticotomy. Distraction osteogenesis of the alveolar ridge as a treatment modality in implant dentistry is a very useful technique that allows for adequate bone formation suitable for implant insertion. Alveolar distraction can be unidirectional, bidirectional, multidirectional or horizontal. Alveolar distraction osteogenesis can be performed by using intraosseous distraction devices, intraosseous distraction implants or by extraosseous devices which are the most prevalent today. Distraction osteogenesis has many advantages such as gradual lengthening of the bone with no need for an autogenous bone graft and lack of the associated donor site morbidity as well as distraction of the surrounding soft tissue together with the transported bone. One of the major challenges when using alveolar distraction osteogenesis is controlling the vector of distraction, this problem should be further addressed in future researches. We describe different methods for alveolar distraction osteogenesis, including the surgical procedure, latency period, lengthening and consolidation period. We also discuss the advantages, disadvantages and complications of the method. In this manuscript a case of mandibular alveolar deficiency following mandibular fracture and loss of teeth and the alveolar bone is presented. This patient was treated by alveolar distraction osteogenesis with excellent results. This patient was later rehabilitated . using endosseous implants as demonstrated by radiographs. Alveolar distraction osteogenesis provides a method to regain both hard tissue and soft tissue without additional grafting and is an efficient modality in cases of medium

  14. LAMB3 mutations causing autosomal-dominant amelogenesis imperfecta.

    Science.gov (United States)

    Kim, J W; Seymen, F; Lee, K E; Ko, J; Yildirim, M; Tuna, E B; Gencay, K; Shin, T J; Kyun, H K; Simmer, J P; Hu, J C-C

    2013-10-01

    Amelogenesis imperfecta (AI) can be either isolated or part of a larger syndrome. Junctional epidermolysis bullosa (JEB) is a collection of autosomal-recessive disorders featuring AI associated with skin fragility and other symptoms. JEB is a recessive syndrome usually caused by mutations in both alleles of COL17A1, LAMA3, LAMB3, or LAMC2. In rare cases, heterozygous carriers in JEB kindreds display enamel malformations in the absence of skin fragility (isolated AI). We recruited two kindreds with autosomal-dominant amelogenesis imperfecta (ADAI) characterized by generalized severe enamel hypoplasia with deep linear grooves and pits. Whole-exome sequencing of both probands identified novel heterozygous mutations in the last exon of LAMB3 that likely truncated the protein. The mutations perfectly segregated with the enamel defects in both families. In Family 1, an 8-bp deletion (c.3446_3453del GACTGGAG) shifted the reading frame (p.Gly 1149Glufs*8). In Family 2, a single nucleotide substitution (c.C3431A) generated an in-frame translation termination codon (p.Ser1144*). We conclude that enamel formation is particularly sensitive to defects in hemidesmosome/basement-membrane complexes and that syndromic and non-syndromic forms of AI can be etiologically related. PMID:23958762

  15. Occurrence of epidermolysis bullosa along with Amelogenesis imperfecta in female patient of India

    Directory of Open Access Journals (Sweden)

    A P Javed

    2013-01-01

    Full Text Available Epidermolysis bullosa (EB is an inherited disorder, which is characteristically presented as skin blisters developing in response to minor injury. Junctional variety of EB is also associated with enamel hypoplasia. Amelogenesis imperfecta presents with abnormal formation of the enamel both in deciduous and permanent dentition. This article describes a previously unreported case of Amelogenesis imperfecta with complete loss of enamel in a young female patient with EB.

  16. An isogenic model of murine mandibular distraction osteogenesis.

    Science.gov (United States)

    Deshpande, Sagar S; Weiss, Daniela M; Donneys, Alexis; Gallagher, Katherine K; Tchanque-Fossuo, Catherine N; Sarhaddi, Deniz; Buchman, Steven R

    2013-03-01

    The advent of stem cell-based therapies makes current models of mandibular distraction osteogenesis unwieldy. We thereby designed an isogenic model of distraction osteogenesis whose purpose was to allow for the free transfer of cells and components between rats. As immune response plays a significant role in healing and prevention of infection, an immune-competent mode is desirable rather than an athymic rat/xenograft model. The purposes of this study were as follows: (1) to replicate established models of distraction osteogenesis in a rodent model using an isogenic rat strain, and (2) to characterize the differences between inbred, isogenic rats and outbred rats in mandibular distraction osteogenesis via radiomorphometry and biomechanical response analysis. We demonstrated successful distraction osteogenesis to 5.1 mm in all Lewis (isogenic) rat mandibles as well as all Sprague-Dawley (outbred) rat mandibles, with no significant difference in volume-normalized radiomorphometrics, trending difference in non-volume-normalized radiomorphometrics and significant differences in biomechanical response parameters. We attribute the differences demonstrated to the decreased size of the Lewis rat mandible in comparison to Sprague-Dawley mandibles. We also provide information with caring with the additional needs of the Lewis rat. Given these differences, we find that Lewis rats function as an excellent model for isogenic mandibular distraction osteogenesis, but data procured may not be comparable between isogenic and nonisogenic models.

  17. Overlapping DSPP mutations cause dentin dysplasia and dentinogenesis imperfecta.

    Science.gov (United States)

    McKnight, D A; Simmer, J P; Hart, P S; Hart, T C; Fisher, L W

    2008-12-01

    Dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) are allelic disorders due to mutations in DSPP. Typically, the phenotype breeds true within a family. Recently, two reports showed that 3 different net -1 bp frameshift mutations early in DSPP's repeat domain caused DD, whereas 6 more 3' frameshift mutations were associated with DGI. Here we identify a DD kindred with a novel -1 bp frameshift (c.3141delC) that falls within the portion of the DSPP repeat domain previously associated solely with the DGI phenotype. This new frameshift mutation shows that overlapping DSPP mutations can give rise to either DGI or DD phenotypes. Furthermore, the consistent kindred presentation of the DD or DGI phenotype appears to be dependent on an as-yet-undescribed genetic modifier closely linked to DSPP.

  18. Multiple teeth fractures in dentinogenesis imperfecta: a case report.

    Science.gov (United States)

    Min, Boram; Song, Je Seon; Lee, Jae-Ho; Choi, Byung-Jai; Kim, Kwang-Mahn; Kim, Seong-Oh

    2014-01-01

    Dentinogenesis imperfecta (DGI) is a hereditary defect consisting of opalescent teeth composed of irregularly formed and hypomineralized dentin. This paper presents the multiple fractures of DGI-affected teeth and suggests the reason of low fracture resistance by observing the dentin microstructures directly using scanning electron microscope (SEM) and by measuring its surface hardness using the Vickers hardness test. SEM revealed that while the enamel microstructure was similar in the DGI-affected and normal teeth, the microstructure of the DGI-affected dentin was poorly woven and more loosely packed than that of the normal dentin. The Vickers hardness of the DGI-affected dentin was 4.89 times softer than the normal dentin. The low fracture resistance of DGI-affected teeth can be attributed to the poorly woven microstructure of their dentin, which leads to a reduction in hardness.

  19. Dentinogenesis imperfecta type II: ultrastructure of teeth in sagittal sections.

    Science.gov (United States)

    Wieczorek, Aneta; Loster, Jolanta

    2013-01-01

    The morphological abnormalities of the teeth of patients affected by dentinogenesis imperfecta type 2 (DI-II) may underlie the difficulties with the clinical restoration of such teeth. We therefore performed a scanning electron microscopy (SEM) study of four permanent first mandibular molars of four DI-II patients with periapical pathosis. The teeth were prepared for SEM evaluation by standard methods. In the crown, the enamel presented a highly irregular surface with a number of cracks and crevices. In some places, only granular remains of the enamel were found, while in other parts of the crown, the enamel was absent. SEM examination revealed the structural changes responsible for the lower enamel's hardness and resistance to attrition, and for tooth wear, while the structural changes in the dentin may explain the failure of some adhesive restorative materials. This SEM study thus revealed structural defects which underlie the problems of attrition and restoration loss found in patients with this genetic dental condition.

  20. Dental rehabilitation of amelogenesis imperfecta using thermoformed templates

    Directory of Open Access Journals (Sweden)

    SNMP Sockalingam

    2011-01-01

    Full Text Available Amelogenesis imperfecta represents a group of dental developmental conditions that are genomic in origin. Hypoplastic AI, hypomineralised AI or both in combination were the most common types seen clinically. This paper describes oral rehabilitation of a 9-year-old Malay girl with inherited hypoplastic AI using transparent thermoforming templates. The defective surface areas were reconstructed to their original dimensions on stone cast models of the upper and lower arches using composite, and transparent thermoform templates were fabricated on the models. The templates were used as crown formers to reconstruct the defective teeth clinically using esthetically matching composite. The usage of the templates allowed direct light curing of the composite, accurate reproducibility of the anatomic contours of the defective teeth, reduced chair-side time and easy contouring and placement of homogenous thickness of composite in otherwise inaccessible sites of the affected teeth.

  1. Amelogenesis imperfecta: Report of a case and review of literature

    Directory of Open Access Journals (Sweden)

    Chaudhary Mayur

    2009-01-01

    Full Text Available Amelogenesis imperfecta (AI is a diverse collection of inherited diseases that exhibit quantitative or qualitative tooth enamel defects in the absence of systemic manifestations. Also known by varied names such as Hereditary enamel dysplasia, Hereditary brown enamel, Hereditary brown opalescent teeth, this defect is entirely ectodermal, since mesodermal components of the teeth are basically normal. The AI trait can be transmitted by either autosomal dominant, autosomal recessive, or X-linked modes of inheritance. Genes implicated in autosomal forms are genes encoding enamel matrix proteins, namely: enamelin and ameloblastin, tuftelin, MMP-20 and kallikrein - 4. This article presents a case reported to Dr. D. Y. Patil, Dental College and Hospital, Pune, India, along with a review of this often seen clinical entity.

  2. Bilateral nephrocalcinosis and amelogenesis imperfecta: A case report

    Directory of Open Access Journals (Sweden)

    Alok Patel

    2015-01-01

    Full Text Available Amelogenesis imperfecta (AI is a group of hereditary disorders that affect the quality and/or quantity of dental enamel. This paper describes the clinicopathological features of a patient who was born of nonconsanguineous parents and who presented with oral alterations, including yellow and misshapen teeth, intrapulpal calcifications, delayed tooth eruption, and gum enlargement. Scanning electron microscopy of the teeth revealed hypoplastic enamel, and a renal ultrasound detected bilateral nephrocalcinosis, leading to a diagnosis of AI and nephrocalcinosis syndrome. Since nephrocalcinosis is often asymptomatic and can be associated with impaired renal function, dentists who see children with a generalized and thin hypoplastic AI should consider a renal ultrasound scan and referral to a Nephrologist. Children with nephrocalcinosis should also be considered for a dental check.

  3. Amelogenesis Imperfecta and Screening of Mutation in Amelogenin Gene

    Directory of Open Access Journals (Sweden)

    Fernanda Veronese Oliveira

    2014-01-01

    Full Text Available The aim of this study was to report the clinical findings and the screening of mutations of amelogenin gene of a 7-year-old boy with amelogenesis imperfecta (AI. The genomic DNA was extracted from saliva of patient and his family, followed by PCR and direct DNA sequencing. The c.261C>T mutation was found in samples of mother, father, and brother, but the mutation was not found in the sequence of the patient. This mutation is a silent mutation and a single-nucleotide polymorphism (rs2106416. Thus, it is suggested that the mutation found was not related to the clinical presence of AI. Further research is necessary to examine larger number of patients and genes related to AI.

  4. Amelogenesis imperfecta: A challenge to restoring esthetics and function

    Directory of Open Access Journals (Sweden)

    Ranganath V

    2010-01-01

    Full Text Available Rehabilitation of complicated cases poses difficulty in clinical practice, both with respect to restoring function and with esthetics. One such clinical condition where the dentist has to give importance to proper planning of the treatment and execution of the plan is amelogenesis imperfecta (AI, a condition where both function and esthetics are accommodated. This article discusses both the functional and esthetic rehabilitation of a patient with AI. Both the esthetics and function were hampered in this patient due to the condition. As a result, the treatment was properly planned and executed. A number of treatment options are available for us today to treat such a case. There is no one technique to be followed as such. However, the aim was to properly diagnose the case and provide good function and esthetics to the patient.

  5. Hereditary gingival hyperplasia associated with amelogenesis imperfecta: a case report.

    Science.gov (United States)

    Nibali, Luigi; Brett, Peter M; Donos, Nikos; Griffiths, Gareth S

    2012-06-01

    Hereditary gingival fibromatosis (HGF) and amelogenesis imperfecta (AI) are two rare oral conditions with genetic etiologies. The case of a 17-year-old boy affected by HGF, AI, anterior open bite, and pyramidal impaction of the maxillary molars is reported. Internal bevel gingivectomies were carried out to reduce gingival overgrowth. Clinical examination of the family revealed the presence of HGF and AI in his 12-year-old sister (both in milder forms) and of HGF in his older half brother. Genetic sequencing analyses were performed to detect any of the known mutations leading to HGF and AI. Histologic analysis revealed the presence of fibroepithelial hyperplasia, consistent with a diagnosis of GF. Sequencing genetic analysis failed to identify any of the common mutations leading to HGF (SOS-1) or AI (enamelin and amelogenin genes). This phenotype, similar to what has been described in other families, may represent a new syndrome caused by an as-yet unknown genotype.

  6. The distraction osteogenesis in midfacial hypoplasia.

    Science.gov (United States)

    Lucchese, Alessandra; Gherlone, Enrico F; Asperio, Paolo; Baena, Ruggero Rodriguez y

    2014-05-01

    Distraction osteogenesis (DO) can generate new bone in a gap between 2 vascularized bone surfaces in response to application of graduated tensile stress across the bone gap. The authors present the clinical result in a cleft patient with severe maxillary deficiency treated by a rigid external distraction (RED) device. A boy complained of both masticatory and psychological problems because of cleft with severe midfacial retrusion. The treatment aimed to create a well-balanced facial profile, increase maxillary incisal display, create proper overjet and overbite, and align his dentition. By the RED system, the traction is applied to the maxilla through the dentition by an intraoral splint. A complete Le Fort I osteotomy was performed, including pterygomaxillary and septal disjunction, with mobilization. Once osteotomy was completed, the halo portion of the RED device was adjusted for the width of the neurocranium and was rigidly fixed around the head with 2 scalp screws on each side. A well-balanced facial profile and a good alignment of the dentition were obtained. The patients had considerable improvement in his self-esteem. Clinical reports have suggested that maxillary advancements achieved by distraction are more stable than those achieved with orthognathic surgery with a minimal influence on velopharyngeal competence.

  7. Quantitative assessment of mineralization in distraction osteogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Hazra, Sunit; Biswal, Sandeep; Jang, Ki-Mo; Modi, Hitesh N. [Korea University, Guro Hospital, Department of Orthopedic Surgery, Seoul (Korea); Song, Hae-Ryong [Rare Diseases Institute, Korea University, Guro Hospital, Department of Orthopedic Surgery, Seoul (Korea); Lee, Suk-Ha [Konkuk University Hospital, Department of Orthopedics, Seoul (Korea); Lee, Seok Hyun [Dongguk University International Hospital, Department of Orthopedic Surgery, Ilsan (Korea)

    2008-09-15

    The most important decision in distraction osteogenesis is the timing of fixator removal. Various methods have been tried, such as radiographic appearance of callus and bone mineral density (BMD) assessment, but none has acquired gold standard status. The purpose of this study was to develop another objective method of assessment of callus stiffness to help clinicians in taking the most important decision of when to remove the fixator. We made a retrospective study of 70 patients to compare the BMD ratio and pixel value ratio. These ratios were calculated at the time of fixator removal, and Pearson's coefficient of correlation was used to show the comparability. Inter- and intra-observer variability of the new method was also tested. Good correlation was found between BMD ratio and pixel value ratio, with a Pearson's coefficient of correlation of 0.79. The interobserver variability was also low, with high intra-observer reproducibility, suggesting that this test was simple to perform. Pixel value ratio is a good method for assessing callus stiffness, and it can be used to judge the timing of fixator removal. (orig.)

  8. Trifocal distraction osteogenesis for reconstruction of skull defect

    Institute of Scientific and Technical Information of China (English)

    Ke Ke; Hai-Song Xu; Zhi-Hong Fan

    2013-01-01

    Objective:To apply trifocal distraction osteogenesis in canine model of skull segmental defects and to provide reference for clinical treatment. Methods:Six labrador dogs were selected in this study and divided into observation group and control group randomly. Each group contained 3 dogs. Skull segmental defects models were established by surgery, and dogs in bservation group received trifocal distraction osteogenesis treatment. Bone density was observed and compared between two groups during treatment. Results: There were no significant difference in bone density between two groups on th 1st day (P>0.05). The bone density of observation group on the 30th day, and 60th day were higher than that of control group (P<0.01). Conclusions: Trifocal distraction osteogenesis has significant clinical effect, and it would be widely used in clinical treatment.

  9. Le fort I maxillary advancement using distraction osteogenesis.

    Science.gov (United States)

    Combs, Patrick D; Harshbarger, Raymond J

    2014-11-01

    Treatment of maxillary hypoplasia has traditionally involved conventional Le Fort I osteotomies and advancement. Advancements of greater than 10 mm risk significant relapse. This risk is greater in the cleft lip and palate population, whose anatomy and soft tissue scarring from prior procedures contributes to instability of conventional maxillary advancement. Le Fort I advancement with distraction osteogenesis has emerged as viable, stable treatment modality correction of severe maxillary hypoplasia in cleft, syndromic, and noncleft patients. In this article, the authors provide a review of current data and recommendations concerning Le Fort I advancement with distraction osteogenesis. In addition, they outline their technique for treating severe maxillary hypoplasia with distraction osteogenesis using internal devices.

  10. Stability after Cleft Maxillary Distraction Osteogenesis or Conventional Orthognathic Surgery

    DEFF Research Database (Denmark)

    Andersen, Kristian; Svenstrup, Martin; Pedersen, Thomas Klit;

    2015-01-01

    OBJECTIVES: To compare stability of maxillary advancements in patients with cleft lip and palate following distraction osteogenesis or orthognathic surgery. MATERIAL AND METHODS: INCLUSION CRITERIA: 1) cleft lip and palate, 2) advancement > 8 mm. Eleven patients comprised the distraction...... changed in CONVG. At follow-up (T3), VOB increased in CONVG compared with DOG, (P = 0.01). Vertical position of A point differed between the groups (P = 0.04). No significant intergroup differences between soft tissue parameters occurred. CONCLUSIONS: Distraction osteogenesis resulted in a stable position...... osteogenesis group (DOG). Seven patients comprised the orthognathic treatment group (CONVG). Skeletal and soft tissue points were traced on lateral cephalograms: T1 (preoperatively), T2 (after surgery), T3 (follow-up). Group differences were analyzed using Students t-test. RESULTS: At T1-T2, advancement of 6...

  11. Analysis and Literature Review of Osteogenesis Imperfect in A Family%成骨不全家系分析并文献复习

    Institute of Scientific and Technical Information of China (English)

    郑峰

    2012-01-01

    Osteogenesis Imperfecta ( OI) is a kind of autosomal dominant or recessive hereditary connective tissue disease and its clinical features are bone fragility and bone deformities. It is very rare in clinic. According to the main clinical symptoms and radiographic results, we found a pedigree with OI. The research in genetics and cytology being more and more thorough, the authors took this pedigree as the foundation and discussed its pathogenesis, diagnosis, treatment and rehabilitation problems. In addition, the relevant literature was reviewed as well.%成骨不全症是以骨脆弱和骨畸形为临床特征的常染色体显性或隐性遗传缺陷的结缔组织病,临床罕见,根据主要临床表现和影像学结果来确诊.现发现成骨不全症家系一例,面对基因学和细胞学正在不断深入的研究,笔者以此家系为基础,对其发病机制、诊断、治疗及康复等问题予以阐述并文献复习.

  12. Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali [Dept. of Conservative Dentistry and Endodontics, Manubhai Patel Dental College, Maharaja Krishnakumarsinhji Bhavnagar University, Vadodara (India)

    2015-09-15

    Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

  13. Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report

    International Nuclear Information System (INIS)

    Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management

  14. Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report.

    Science.gov (United States)

    Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali

    2015-09-01

    Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

  15. Amelogenesis Imperfecta with Taurodontism, Microdontia, and Minor Thalassemia: A Case Report

    Directory of Open Access Journals (Sweden)

    Fatemeh Mazhari

    2013-12-01

    Full Text Available Amelogenesis imperfecta is a group of genetic disorders that affects both the morphology and quality of tooth structure. Although the disease entity is primarily associated with abnormalities of dental and oral structures, it has been reported to be associated with a few syndromes. A 9-year-old girl with minor thalassemia referred to the Department of Pediatric Dentistry of the Mashhad Faculty of Dentistry with a complaint of sensitivity of first permanent molars. Dental findings consisted of amelogenesis imperfecta, microdontia, posterior cross bite and taurodontism. This is the first report of thalassemia accompanied with amelogenesis imperfecta. Although the patients often are non-symptomatic, the trait can be passed on to a child and if both parents carry the trait, the child could develop a more severe form of the disease; therefore, early diagnosis is important.

  16. Exonal deletion of SLC24A4 causes hypomaturation amelogenesis imperfecta.

    Science.gov (United States)

    Seymen, F; Lee, K-E; Tran Le, C G; Yildirim, M; Gencay, K; Lee, Z H; Kim, J-W

    2014-04-01

    Amelogenesis imperfecta is a heterogeneous group of genetic conditions affecting enamel formation. Recently, mutations in solute carrier family 24 member 4 (SLC24A4) have been identified to cause autosomal recessive hypomaturation amelogenesis imperfecta. We recruited a consanguineous family with hypomaturation amelogenesis imperfecta with generalized brown discoloration. Sequencing of the candidate genes identified a 10-kb deletion, including exons 15, 16, and most of the last exon of the SLC24A4 gene. Interestingly, this deletion was caused by homologous recombination between two 354-bp-long homologous sequences located in intron 14 and the 3' UTR. This is the first report of exonal deletion in SLC24A4 providing confirmatory evidence that the function of SLC24A4 in calcium transport has a crucial role in the maturation stage of amelogenesis.

  17. Cordycepin prevents oxidative stress-induced inhibition of osteogenesis.

    Science.gov (United States)

    Wang, Feng; Yin, Peipei; Lu, Ye; Zhou, Zubin; Jiang, Chaolai; Liu, Yingjie; Yu, Xiaowei

    2015-11-01

    Oxidative stress is known to be involved in impairment of osteogenesis and age-related osteoporosis. Cordycepin is one of the major bioactive components of Cordyceps militaris that has been shown to exert antioxidant and anti-inflammatory activities. However, there are few reports available regarding the effects of cordycepin on osteogenesis and the underlying mechanism. In this study, we investigated the potential osteoprotective effects of cordycepin and its mechanism systematically using both in vitro model as well as in vivo mouse models. We discovered that hydrogen peroxide (H2O2)-induced inhibition of osteogenesis which was rescued by cordycepin treatment in human bone marrow mesenchymal stem cells (BM-MSCs). Cordycepin exerted its protective effects partially by increasing or decreasing expression of osteogenic and osteoclastogenesis marker genes. Treatment with cordycepin increased Wnt-related genes' expression whereas supplementation of Wnt pathway inhibitor reversed its protective effects. In addition, administration of cordycepin promoted osteogenic differentiation of BM-MSCs by reducing oxidative stress in both ovariectomized and aged animal models. Taken together, these results support the protective effects of cordycepin on oxidative stress induced inhibition of osteogenesis by activation of Wnt pathway. PMID:26462178

  18. Distraction osteogenesis in the irradiated mandible. A case report

    NARCIS (Netherlands)

    Raghoebar, GM; Jansma, J; Vissink, A; Roodenburg, JLN

    2005-01-01

    Background: Distraction osteogenesis has been suggested as a relatively simple method of mandibular reconstruction following ablative head and neck surgery. Some authors report good results in irradiated patients while other authors report limitations with this group of patients. Patient: In a 72-ye

  19. Upper airway outcomes following midface distraction osteogenesis: a systematic review.

    Science.gov (United States)

    Taylor, B A; Brace, M; Hong, P

    2014-07-01

    The objective of this paper is to systematically review the airway outcomes following distraction osteogenesis of midface with the goal of (1) deriving clinically oriented insights and (2) identifying gaps in knowledge to stimulate future research. Medline, EMBASE and Cochrane databases were searched and studies were included if subjects of any age had midface retrusion/hypoplasia and underwent midface distraction osteogenesis. Outcome measures of interest were any respiratory or airway associated measures, and reports of adverse events. A total of 368 abstracts were generated from the literature searches; 16 studies met the criteria for data extraction and analysis. All 16 studies were observational. Generally, midface distraction osteogenesis was reported to improve respiratory status and was well tolerated. Specifically, favorable outcomes in cephalometry (9 studies), polysomnography (9 studies), and decannulation rates (8 studies) were reported. In conclusion, upper airway status was improved in most patients who underwent midface distraction osteogenesis, yet long-term results and consistent objective measures are lacking. Studies reviewed were retrospective case series and details regarding patients who did not improve were deficient. A standardized prospective multicenter cohort trial with long-term patient follow up is required.

  20. Backward distraction osteogenesis in a patient with severe mandibular micrognathia.

    Science.gov (United States)

    Mitsukawa, Nobuyuki; Morishita, Tadashi; Saiga, Atsuomi; Akita, Shinsuke; Kubota, Yoshitaka; Satoh, Kaneshige

    2013-09-01

    Maxillary skeletal prognathism can involve severe mandibular micrognathia with marked mandibular retrognathism or hypoplasia. For patients with such a condition, a conventional treatment is mandibular advancement by sagittal split ramus osteotomy (SSRO). This procedure has problems such as insufficient advancement, instability of jaw position, and postoperative relapse. Thus, in recent years, mandibular distraction osteogenesis has been used in some patients. Mandibular distraction has many advantages, but an ideal occlusion is difficult to achieve using this procedure. That is, 3-dimensional control cannot be attained using an internal device that is unidirectional. This report describes a case of severe mandibular micrognathia in a 14-year-old girl treated using backward distraction osteogenesis. This procedure was first reported by Ishii et al (Jpn J Jaw Deform 2004; 14:49) and involves a combination of SSRO and ramus distraction osteogenesis. In the present study, intermaxillary fixation in centric occlusion was performed after osteotomy, and proximal bone segments were distracted in a posterosuperior direction. This procedure is a superior surgical technique that avoids the drawbacks of SSRO and conventional mandibular distraction. However, it applies a large load to the temporomandibular joints and requires thorough management. Thus, careful evaluation needs to be made of the indication for backward distraction osteogenesis.

  1. Dentinogenesis imperfecta - hardness and Young's modulus of teeth.

    Science.gov (United States)

    Wieczorek, Aneta; Loster, Jolanta; Ryniewicz, Wojciech; Ryniewicz, Anna M

    2013-01-01

    Dentinogenesis imperfecta type II (DI-II) is the most common dental genetic disease with reported incidence 1 in 8000. Elasticity and hardness of the enamel of teeth are important values which are connected with their resistance to attrition. It is hypothesized that values of physical properties for healthy teeth and teeth with DI-II are different. The aim of the study was to investigate some physical properties of teeth extracted from patients with DI-II in comparison with normal teeth. The material of the study was six teeth: three lower molars, with clinical signs of DI-II, which were extracted due to complications of pulp inflammation and three other lower molars which were extracted for orthodontic reasons - well formed, without any signs of pathology. The surfaces of DI-II and normal teeth were tested on the CSM Instruments Scratch Tester machine (producer CSEM Switzerland) by Oliver and Pharr method. The indenter used was Vicker's VG-73 diamond indenter. Additionally, the Scanning Electron Microscopy (SEM) analysis of the surface of the teeth with DI-II was made. Vickers hardness of the teeth with dental pathology (DI-II) was seven times smaller, and Young's modulus six times smaller than those of healthy teeth. The parameters of hardness and elasticity of enamel of teeth with clinical diagnosis of DI-II were very much smaller than in normal teeth and because of that can be responsible for attrition.

  2. Genetic mapping of the dentinogenesis imperfecta type II locus

    Energy Technology Data Exchange (ETDEWEB)

    Crosby, A.H.; Dixon, M.J. [Univ. of Manchester (United Kingdom); Scherpbier-Heddema, T. [Fox Chase Cancer Center, Philadelphia, PA (United States)] [and others

    1995-10-01

    Dentinogenesis imperfecta type II (DGI-II) is an autosomal dominant disorder of dentin formation, which has previously been mapped to chromosome 4q12-21. In the current study, six novel short tandem-repeat polymorphisms (STRPs) have been isolated, five of which show significant evidence of linkage to DGI-II. To determine the order of the STRPs and define the genetic distance between them, nine loci (including polymorphisms for two known genes) were mapped through the CEPH reference pedigrees. The resulting genetic map encompasses 16.3 cM on the sex-averaged map. To combine this map with a physical map of the region, all of the STRPs were mapped through a somatic cell hybrid panel. The most likely location for the DGI-II locus within the fixed marker map is in the D4S2691-D4S2692 interval of 6.6 cM. The presence of a marker that shows no recombination with the DGI-II phenotype between the flanking markers provides an important anchor point for the creation of physical continuity across the DGI-II candidate region. 38 refs., 4 figs., 2 tabs.

  3. Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II.

    Science.gov (United States)

    Lee, K-E; Kang, H-Y; Lee, S-K; Yoo, S-H; Lee, J-C; Hwang, Y-H; Nam, K H; Kim, J-S; Park, J-C; Kim, J-W

    2011-04-01

    The dentin sialophosphoprotein (DSPP) gene encodes the most abundant non-collagenous protein in tooth dentin and DSPP protein is cleaved into several segments including the highly phosphorylated dentin phosphoprotein (DPP). Mutations in the DSPP gene have been solely related to non-syndromic form of hereditary dentin defects. We recruited three Korean families with dentinogenesis imperfecta (DGI) type II and sequenced the exons and exon-intron boundaries of the DSPP gene based on the candidate gene approach. Direct sequencing of PCR products and allele-specific cloning of the highly repetitive exon 5 revealed novel single base pair (bp) deletional mutations (c.2688delT and c.3560delG) introducing hydrophobic amino acids in the hydrophilic repeat domain of the DPP coding region. All affected members of the three families showed exceptionally rapid pulp chambers obliteration, even before tooth eruption. Individuals with the c.3560delG mutation showed only mild, yellowish tooth discoloration, in contrast to the affected individuals from two families with c.2688delT mutation. We believe that these results will help us to understand the molecular pathogenesis of DGI type II as well as the normal process of dentin biomineralization.

  4. Prosthetic treatment in dentinogenesis imperfecta type II: a case report

    Directory of Open Access Journals (Sweden)

    Sedat Güven

    2016-05-01

    Full Text Available INTRODUCTION: Dentinogenesis imperfecta (DI or hereditary opalescent dentin is an autosomal dominant disorder affecting both primary and permanent dentition. Early diagnosis and treatment of DI is important for normal facial growth and esthetic continuity by preserving occlusion and tooth structure. It also provides psychological motivation by increasing the patient’s quality of life. Providing functional dentition in DI patients prevents loss of the vertical dimension, while enabling normal growth of the facial bones and jaw joint. CASE REPORT: A 20-year-old male with DI was referred to our clinic with chewing difficulty and esthetic and speech problems. His brother also had this disease. Oral examination showed the loss of many teeth and the absence of enamel on most of the remaining teeth, causing discoloration and exposing soft dentinal tissue with calcification disorder. Despite widespread attrition of the teeth, pulp chambers were not exposed. The tip of the lower jaw was prominent in the patient’s profile. Placing metal-ceramic fixed dentures in the lower jaw and an overdenture prosthesis in the upper jaw improved the patient’s psychological state as well as his function, phonation, and esthetics. CONCLUSION: This case report presents the intraoral findings in a patient with DI, including the histopathological findings, and the prosthetic treatment approach and the treatment outcome.

  5. Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta.

    Science.gov (United States)

    Poulter, James A; Murillo, Gina; Brookes, Steven J; Smith, Claire E L; Parry, David A; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-10-15

    Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is the second most abundant enamel matrix protein expressed during amelogenesis. The pivotal role of AMBN in amelogenesis has been confirmed experimentally using mouse models. However, no AMBN mutations have been associated with human AI. Using autozygosity mapping and exome sequencing, we identified genomic deletion of AMBN exon 6 in a second cousin consanguineous family with three of the six children having hypoplastic AI. The genomic deletion corresponds to an in-frame deletion of 79 amino acids, shortening the protein from 447 to 368 residues. Exfoliated primary teeth (unmatched to genotype) were available from family members. The most severely affected had thin, aprismatic enamel (similar to that reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth exhibited thicker but largely aprismatic enamel. One tooth had apparently normal enamel. It has been suggested that AMBN may function in bone development. No clinically obvious bone or other co-segregating health problems were identified in the family investigated. This study confirms for the first time that AMBN mutations cause non-syndromic human AI and that mouse models with disrupted Ambn function are valid.

  6. No Evidence for Association between Amelogenesis Imperfecta and Candidate Genes

    Directory of Open Access Journals (Sweden)

    M Ghandehari Motlagh

    2009-03-01

    Full Text Available "nBackground: Amelogenesis imperfecta (AI is an inherited tooth disorder. Despite the fact that up to now, several gene muta­tions in MMP20, ENAM, AMELX and KLK4 genes have been reported to be associated with AI, many other genes sug­gested to be involved. The main objective of this study was to find the mutations in three major candidate genes including MMP20, ENAM and KLK4 responsible for AI from three Iranian families with generalized hypoplastic phenotype in all teeth. "nMethods: All exon/intron boundaries of subjected genes were amplified by polymerase chain reaction and subjected to direct sequencing."nResults: One polymorphisms was identified in KLK4 exon 2, in one family a homozygous mutation was found in the third base of codon 22 for serine (TCG>TCT, but not in other families. Although these base substitutions have been occurred in the signaling domain, they do not seem to influence the activity of KLK4 protein."nConclusion: Our results might support the further evidence for genetic heterogeneity; at least, in some AI cases are not caused by a gene in these reported candidate genes.

  7. Adenovirus gene transfer to amelogenesis imperfecta ameloblast-like cells.

    Directory of Open Access Journals (Sweden)

    Anton V Borovjagin

    Full Text Available To explore gene therapy strategies for amelogenesis imperfecta (AI, a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5 vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR on those cells relative to CAR-positive A549 cells. To overcome CAR -deficiency, we evaluated capsid-modified Ad5 vectors with various genetic capsid modifications including "pK7" and/or "RGD" motif-containing short peptides incorporated in the capsid protein fiber as well as fiber chimera with the Ad serotype 3 (Ad3 fiber "knob" domain. All fiber modifications provided an augmented transduction of AI-ameloblasts, revealed following vector dose normalization in A549 cells with a superior effect (up to 404-fold of pK7/RGD double modification. This robust infectivity enhancement occurred through vector binding to both α(vβ3/α(vβ5 integrins and heparan sulfate proteoglycans (HSPGs highly expressed by AI-ameloblasts as revealed by gene transfer blocking experiments. This work thus not only pioneers establishment of human AI ameloblast-like cell population as a model for in vitro studies but also reveals an optimal infectivity-enhancement strategy for a potential Ad5 vector-mediated gene therapy for AI.

  8. OI Issues: Dental Care for Persons with OI

    Science.gov (United States)

    ... oral problems in an osteogenesis imperfecta population, Oral Surgery Oral Med Oral Pathol Oral Radiol Endod ; 87: 189- ... Oral Findings in Patients with Osteogenesis Imperfecta, Oral Surgery. Oral Med. & Oral Path; 57:161-7. (1984). Resource: ...

  9. Prosthetic and Surgical Approach for Oral Rehabilitation in a Patient with Amelogenesis Imperfecta: A Clinical Report

    Directory of Open Access Journals (Sweden)

    H. Sazegara

    2007-06-01

    Full Text Available Amelogenesis imperfecta is a heterogeneous group of hereditary disorders. Its treatment continues throughout the patients’ childhood and adolescence and consists of advanced restorative care in severe cases.A thorough prosthodontic treatment plan including orthognatic surgery, full veneer crowns and all ceramic anterior crowns is presented in this clinical report.

  10. Hypomaturation Amelogenesis Imperfecta Caused By A Novel SLC24A4 Mutation

    Science.gov (United States)

    Herzog, Curtis R.; Reid, Bryan M.; Seymen, Figen; Koruyucu, Mine; Tuna, Elif Bahar; Simmer, James P.; Hu, Jan C-C.

    2014-01-01

    In this case report of autosomal recessive pigmented hypomaturation amelogenesis imperfecta (AI), we identify a novel homozygous missense mutation (g.165151T>G; c.1317T>G; p.Leu436Arg) in SLC24A4, a gene encoding a potassium-dependent sodium-calcium exchanger that is critical for hardening dental enamel during tooth development. PMID:25442250

  11. A potential role for tetranectin in mineralization during osteogenesis

    DEFF Research Database (Denmark)

    Wewer, U M; Ibaraki, K; Schjørring, P;

    1994-01-01

    cartilage or in the surrounding skeletal muscle. Using an in vitro mineralizing system, we examined osteoblastic cells at different times during their growth and differentiation. Tetranectin mRNA appeared in the cultured osteoblastic cells in parallel with mineralization, in a pattern similar...... osteogenesis. In conclusion, we have established a potential role for tetranectin as a bone matrix protein expressed in time and space coincident with mineralization in vivo and in vitro....

  12. Are Endogenous BMPs Necessary for Bone Healing during Distraction Osteogenesis?

    OpenAIRE

    Alam, Norine; St-Arnaud, René; Lauzier, Dominique; Rosen, Vicki; Hamdy, Reggie C.

    2009-01-01

    Previous reports suggest the application of exogenous BMPs can accelerate bone formation during distraction osteogenesis (DO). However, there are drawbacks associated with the use of exogenous BMPs. A possible alternative to the use of exogenous BMPs is to upregulate the expression of endogenous BMPs. Since DO results in spontaneously generated de novo bone formation in a uniform radiographic, histological, and biomechanical temporal sequence, a genetically engineered model lacking endogenous...

  13. Clinical and experimental studies of osteogenesis in dogs

    OpenAIRE

    Theyse, L.F.H.

    2006-01-01

    Growth hormone stimulates bone healing Bone is one of the few tissues capable of complete regeneration. The mechanisms behind this phenomenon are of great interest not only in understanding the process of bone formation, but also in gaining insight into the regeneration of non-skeletal tissues. Distraction osteogenesis, in which bone formation is induced under gradual distraction of two bone surfaces, can be used both as an orthopaedic treatment option and as an experimental model to investig...

  14. Experimental model of distraction osteogenesis in edentulous rats

    OpenAIRE

    Maria Montserrat Pujadas Bigi; Marianela Lewicki; Angela Matilde Ubios; Patricia Monica Mandalunis

    2011-01-01

    Distraction osteogenesis (DO) is a surgical technique producing bone lengthening by distraction of the fracture callus. Although a large number of experimental studies on the events associated with DO of craniofacial skeleton have been reported, the few employing rat mandibular bone DO used complicated designs and produced a small volume of newly formed bone. Thus, this study aims to present an original experimental model of mandibular DO in edentulous rats that produces a sufficient quantity...

  15. Osteogenesis process of tricalcium phosphate ceramics in vivo

    Institute of Scientific and Technical Information of China (English)

    戴红莲; 李世普; 闫玉华; 李小溪; 贾莉

    2003-01-01

    To investigate the osteogenesis of calcium phosphate ceramics, β-TCP ceramics were implanted into thecondyle femur of rabbits, and tetracycline was injected termly. Specimens were host at 1, 2, 3, 4, 5, 6 months af-ter implanted. The new bone formation and osteogenesis process were observed by the histomorphology, fluorescentmicroscope, SEM and EPMA. The results demonstrate that, osteogenesis is active, there are abundant osteoblastson the surface of osteoid, mesenchymal cell hyperplasia and incursion is found in materials after 1 month. After 2months, there is blood vessel formation and macrophage soakage within materials. Bone-island appears and connectsby bone-bridge after 3 months. β-TCP ceramics degrade and are dispersed by new formation bone. Woven boneturns into bone lamella by rebuilding and calcification. The materials entirely change their original shape and com-bines with bone tissue as a whole after 6 months. The typical structure of spongy bone forms. It is confirmed thatβ-TCP is a degradable biocompatible artificial bone material which can incorporating in life.

  16. Distraction osteogenesis after irradiation in a rabbit model

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Kenji [Kanazawa Univ. (Japan). Graduate School of Medical Science

    2002-06-01

    Little is known about how preoperative irradiation delays distraction osteogenesis. The purpose of this study is to investigate the effect of preoperative irradiation on distraction osteogenesis. A single dose of 15 Gy irradiation was applied in a medial-to-lateral direction to the right rear legs of Japanese white rabbits. This was followed immediately by application of a unilateral external fixator and diaphyseal osteotomy of the tibia. Seven days later, lengthening of the tibia was initiated at a rate of 0.5 mm/day and continued for 4 weeks, with a total elongation of 14 mm. Radiographic and histological findings and microangiography were examined. Radiographs of the legs were obtained once a week. The animals were sacrificed at 0 and 4 weeks after completion of lengthening, and the tibia were subjected to histological examination and microangiography. Routine staining was performed with hematoxyline and eosin, and immunostaining with a vascular endothelial growth factor (VEGF) antibody. The radiographs showed little regeneration during the elongation phase. Although the callus appeared very slowly during the maturation phase, it did not show the usual three distinct zones, but only spotty callus formation. Furthermore, regeneration was not completed until the 4th week of the maturation period. The histological examination at the end of distraction showed a gap in the distraction, consisting of loose connective tissue with part of the fibrous tissue oriented longitudinally. There was no evidence of new mineralization. Four weeks after completion of distraction, the major part of the radiolucent region consisted of cartilage. There was no evidence of the normal regeneration pattern described in many previous reports. The spotty osteogenesis was identified as endochondral ossification. Immunochemical examination of the regeneration area revealed that the blood vessels were extremely localized, and that expression of VEGF in the osteoblasts was very high

  17. Skeletal phenotypes in adult patients with osteogenesis imperfecta-correlations with COL1A1/COL1A2 genotype and collagen structure

    DEFF Research Database (Denmark)

    Hald, J D; Folkestad, L; Harsløf, T;

    2016-01-01

    with the underlying biochemical and molecular abnormalities. INTRODUCTION: OI is a hereditary disease characterized by compromised connective tissue predominantly caused by mutations in collagen type 1 (COL-1) encoding genes. Widespread symptoms reflect the ubiquity of COL-1 throughout the body. The purpose...... of this study was to improve our understanding of clinical manifestations by investigating anthropometry and skeletal phenotypes (DXA, HRpQCT) in an adult OI population and compare the findings to underlying COL-1 genotype and structure. METHODS: The study comprised 85 OI patients aged 45 (19-78) years......, Sillence type I (n = 58), III (n = 12), and IV (n = 15). All patients underwent DXA, HRpQCT, spine X-ray, biochemical testing, and anthropometry. COL1A1 and COL1A2 were sequenced and 68 OI causing mutations identified (46 in COL1A1, 22 in COL1A2). Analysis of COL-1 structure (quantitative...

  18. Determinantes da marcha independente na osteogênese imperfeita Independent walk in osteogenesis imperfect

    Directory of Open Access Journals (Sweden)

    Carmem Lia Martins Moreira

    2011-01-01

    Full Text Available OBJETIVOS: Investigar o processo de locomoção em pacientes com osteogênese imperfeita (OI e os fatores que o influenciam, sublinhando pontos clínicos relevantes à reabilitação motora. MÉTODOS: Estudo transversal, retrospectivo, realizado no ambulatório de fisioterapia motora do Instituto Fernandes Figueira. Foram incluídos todos os pacientes com diagnóstico clínico de OI. Foram excluídos os que apresentavam comorbidades e idade inferior a dois anos. Utilizou-se o Epi-Info versão 3.4 para construção do banco de dados e o SPSS versão 15 para análise estatística. Foi calculado risco relativo para mensurar associação de características clínicas com a marcha independente, adotando-se nível de significância de 5% para as análises. RESULTADOS: Foram incluídos 69 pacientes. Dentre eles, 43,5% tinham OI tipo I; 37,7% tipo III e 18,8% tipo IV. 76,8% apresentavam deformidades em ossos longos. Observou-se associação negativa entre hipotonia, número de fraturas e marcha independente e positiva entre marcha independente e OI tipo I. CONCLUSÕES: A clínica fisioterápica, como complementar à ortopédica e à administração de fármacos da família dos bifosfonatos, é de fundamental importância para a reabilitação da capacidade motora dos indivíduos com OI. Nivel de Evidência, estudos transversais.OBJECTIVES: Investigation of the locomotion process in patients with osteogenesis imperfecta (OI, and the factors that influence it, with special attention to clinical aspects relating to motor rehabilitation. METHODS: a retrospective, cross-sectional study was carried out at the physical therapy outpatient clinic of the Instituto Fernandes Figueira. All patients with a clinical diagnosis of OI were included. Patients with other diseases, and those aged under two years, old were excluded. Epi-Info version 3.4 was used to construct the database, and SPSS version 15 for the statistical analysis. RESULTS: The odds-ratio was used to

  19. Complications of mandibular distraction osteogenesis for acquired deformities: a systematic review of the literature

    NARCIS (Netherlands)

    C.R.A. Verlinden; S.E.C.M. van de Vijfeijken; D.B. Tuinzing; A.G. Becking; G.R.J. Swennen

    2015-01-01

    A systematic review on complications in all forms of mandibular distraction osteogenesis (MDO) for acquired deformities was performed. Search terms expressing distraction osteogenesis were used in ‘AND’ combination with search terms comprising ‘mandible’ and terms for complication, failure, and morb

  20. Complications of mandibular distraction osteogenesis for developmental deformities: a systematic review of the literature

    NARCIS (Netherlands)

    C.R.A. Verlinden; S.E.C.M. van de Vijfeijken; D.B. Tuinzing; E.P. Jansma; A.G. Becking; G.R.J. Swennen

    2015-01-01

    A systematic review of English and non-English articles on the complications of mandibular distraction osteogenesis (MDO) for patients with developmental deformities was performed, in accordance with the PRISMA statement. Search terms expressing distraction osteogenesis were used in ‘AND’ combinatio

  1. A novel mutation in the DSPP gene associated with dentinogenesis imperfecta type II.

    Science.gov (United States)

    Lee, S-K; Lee, K-E; Jeon, D; Lee, G; Lee, H; Shin, C-U; Jung, Y-J; Lee, S-H; Hahn, S-H; Kim, J-W

    2009-01-01

    Hereditary dentin defects are divided into dentinogenesis imperfecta and dentin dysplasia. We identified a family segregating severe dentinogenesis imperfecta. The kindred spanned four generations and showed an autosomal-dominant pattern of inheritance. The proband was a child presenting with a severely affected primary dentition, with wide-open pulp chambers and multiple pulp exposures, resembling a DGI type III (DGI-III) pattern. We hypothesized that a mutation in the DSPP gene is responsible for this severe phenotype. Mutational analyses revealed a novel mutation (c.53T>A, p.V18D) near the intron-exon boundary in the third exon of the DSPP gene. We analyzed the effect of the mutation by means of an in vitro splicing assay, which revealed that the mutation did not affect pre-mRNA splicing. Further studies are needed for a better understanding of the nature of the disease and the development of an appropriate treatment strategy.

  2. Defining a new candidate gene for amelogenesis imperfecta: from molecular genetics to biochemistry.

    Science.gov (United States)

    Urzúa, Blanca; Ortega-Pinto, Ana; Morales-Bozo, Irene; Rojas-Alcayaga, Gonzalo; Cifuentes, Víctor

    2011-02-01

    Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypocalcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis imperfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene.

  3. Dental management of amelogenesis imperfecta patients: a primer on genotype-phenotype correlations.

    Science.gov (United States)

    Ng, F K; Messer, L B

    2009-01-01

    Amelogenesis imperfecta (AI) represents a group of hereditary conditions which affects enamel formation in the primary and permanent dentitions. Mutations in genes critical for amelogenesis result in diverse phenotypes characterized by variably thin and/or defective enamel. To date, mutations in 5 genes are known to cause AI in humans. Understanding the molecular etiologies and associated inheritance patterns can assist in the early diagnosis of this condition. Recognition of genotype-phenotype correlations will allow clinicians to guide genetic testing and select appropriate management strategies for patients who express different phenotypes. The purpose of this paper was to provide a narrative review of the current literature on amelogenesis imperfecta, particularly regarding recent advances in the identification of candidate genes and the patterns of inheritance.

  4. Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation

    DEFF Research Database (Denmark)

    Haubek, Dorte; Gjørup, Hans; Jensen, Lillian Gryesten;

    2011-01-01

    Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation......Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation...

  5. Sympathetic Denervation-Induced MSC Mobilization in Distraction Osteogenesis Associates with Inhibition of MSC Migration and Osteogenesis by Norepinephrine/adrb3

    OpenAIRE

    Du, Zhaojie; Wang, Lei; Zhao, Yinghua; Cao, Jian; Tao WANG; Liu, Peng; Zhang, Yabo; Yang, Xinjie; Cheng, Xiaobing; Liu, Baolin; Lei, Delin

    2014-01-01

    The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympath...

  6. Diagnostic features and pedodontic-orthodontic management in dentinogenesis imperfecta type II: a case report.

    Science.gov (United States)

    Huth, K Ch; Paschos, E; Sagner, T; Hickel, R

    2002-09-01

    Dentinogenesis imperfecta type II, also known as hereditary opalescent dentin, is an isolated inherited condition transmitted as an autosomal dominant trait affecting the primary and permanent dentition. The combined pedodontic-orthodontic management of a 4-year-old child is described. Following orthodontic analysis to encourage a favourable growth outcome, treatment comprised restoration of the primary teeth with stainless steel crowns and composite crowns. Differential diagnosis and alternative therapies, including orthodontic considerations, are discussed.

  7. Dentinogenesis imperfecta: a case report of comprehensive treatment for a teenager.

    Science.gov (United States)

    Biethman, Rick; Capati, Laura Richards; Eldger, Nicole

    2014-01-01

    Improving a smile can change a person's self-image. This case report describes treatment for an adolescent boy with dentinogenesis imperfecta. Soon to begin high school, the 14-year-old patient was severely obese and disliked his stained teeth. A combination of surgical periodontal treatment, endodontic treatment, and veneers improved both his smile and self-perception-which may have played a role in achieving his weight loss goal of 125 lb at 12 months post-treatment.

  8. Dentinogenesis imperfecta: A review and case report of a family over four generations

    Directory of Open Access Journals (Sweden)

    Bhandari Sudhir

    2008-01-01

    Full Text Available Dentinogenesis imperfecta (DGI is one of the most common hereditary disorders of dentin formation. It follows an autosomal dominant pattern of transmission, affecting both the formation and mineralization of dentin. Either or both primary and permanent dentition is affected by it. This paper briefly reviews the manifestations of DGI Type II (DGI1 and presents a case report of a family affected with DGI1 over four generations.

  9. Dentinogenesis imperfecta: a review and case report of a family over four generations.

    Science.gov (United States)

    Bhandari, Sudhir; Pannu, Karneev

    2008-01-01

    Dentinogenesis imperfecta (DGI) is one of the most common hereditary disorders of dentin formation. It follows an autosomal dominant pattern of transmission, affecting both the formation and mineralization of dentin. Either or both primary and permanent dentition is affected by it. This paper briefly reviews the manifestations of DGI Type II (DGI1) and presents a case report of a family affected with DGI1 over four generations.

  10. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    OpenAIRE

    Maria Carolina Salomé Marquezin; Bruna Raquel Zancopé; Larissa Ferreira Pacheco; Maria Beatriz Duarte Gavião; Fernanda Miori Pascon

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars wit...

  11. Missense Mutation in Fam83H Gene in Iranian Patients with Amelogenesis Imperfecta.

    Directory of Open Access Journals (Sweden)

    S Jalal Pourhashemi

    2014-12-01

    Full Text Available Amelogenesis Imperfecta (AI is a disorder of tooth development where there is an abnormal formation of enamel or the external layer of teeth. The aim of this study was to screen mutations in the four most important candidate genes, ENAM, KLK4, MMP20 and FAM83H responsible for amelogenesis imperfect.Geneomic DNA was isolated from five Iranian families with 22 members affected with enamel malformations. The PCR amplifications were typically carried out for amplification the coding regions for AI patients and unaffected family members. The PCR products were subjected to direct sequencing. The pedigree analysis was performed using Cyrillic software.One family had four affected members with autosomal dominant hypocalcified amelogenesis imperfecta (ADHPCAI; pedigree analysis revealed four consanguineous families with 18 patients with autosomal recessive hypoplastic amelogenesis imperfecta (ARHPAI. One non-synonymous single-nucleotide substitution, c.1150T>A, p. Ser 342Thr was identified in the FAM83H, which resulted in ADHCAI. Furthermore, different polymorphisms or unclassified variants were detected in MMP20, ENAM and KLK4.Our results are consistent with other studies and provide further evidence for pathogenic mutations of FAM83H gene. These findings suggest different loci and genes could be implicated in the pathogenesis of AI.

  12. The epitheliogenesis imperfecta locus maps to equine chromosome 8 in American Saddlebred horses.

    Science.gov (United States)

    Lieto, L D; Cothran, E G

    2003-01-01

    Epitheliogenesis imperfecta (EI) is a hereditary junctional mechanobullous disease that occurs in newborn American Saddlebred foals. The pathological signs of epitheliogenesis imperfecta closely match a similar disease in humans known as Herlitz junctional epidermolysis bullosa, which is caused by a mutation in one of the genes (LAMA3, LAMB3 and LAMC2) coding for the subunits of the laminin 5 protein (laminin alpha3, laminin beta3 and laminin gamma2). The LAMA3 gene has been assigned to equine chromosome 8 and LAMB3 and LAMC2 have been mapped to equine chromosome 5. Linkage disequilibrium between microsatellite markers that mapped to equine chromosome 5 and equine chromosome 8 and the EI disease locus was tested in American Saddlebred horses. The allele frequencies of microsatellite alleles at 11 loci were determined for both epitheliogenesis imperfecta affected and unaffected populations of American Saddlebred horses by genotyping and direct counting of alleles. These were used to determine fit to Hardy-Weinberg equilibrium for control and EI populations using Chi square analysis. Two microsatellite loci located on equine chromosome 8q, ASB14 and AHT3, were not in Hardy-Weinberg equilibrium in affected American Saddlebred horses. In comparison, all of the microsatellite markers located on equine chromosome 5 were in Hardy-Weinberg equilibrium in affected American Saddlebred horses. This suggested that the EI disease locus was located on equine chromosome 8q, where LAMA3 is also located. PMID:14970704

  13. Adiponectin Promotes Human Jaw Bone Marrow Stem Cell Osteogenesis.

    Science.gov (United States)

    Pu, Y; Wu, H; Lu, S; Hu, H; Li, D; Wu, Y; Tang, Z

    2016-07-01

    Human jaw bone marrow mesenchymal stem cells (h-JBMMSCs) are multipotent progenitor cells with osteogenic differentiation potential. The relationship between adiponectin (APN) and the metabolism of h-JBMMSCs has not been fully elucidated, and the underlying mechanism remains unclear. The aim of the study was to investigate the effect and mechanism of APN on h-JBMMSC metabolism. h-JBMMSCs were obtained from the primary culture of human jaw bones and treated with or without APN (1 µg/mL). Osteogenesis-related gene expression was evaluated by real-time polymerase chain reaction (PCR), alkaline phosphatase (ALP) activity assay, and enzyme-linked immunosorbent assay (ELISA). To further investigate the signaling pathway, mechanistic studies were performed using Western blotting, immunofluorescence, lentiviral transduction, and SB202190 (a specific p38 inhibitor). Alizarin Red staining showed that APN promoted h-JBMMSC osteogenesis. Real-time PCR, ALP assay, and ELISA showed that ALP, osteocalcin (OCN), osteopontin, and integrin-binding sialoprotein were up-regulated in APN-treated cells compared to untreated controls. Immunofluorescence revealed that adaptor protein containing a pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif (APPL1) translocated from the nucleus to the cytoplasm with APN treatment. Additionally, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) increased over time with APN treatment. Moreover, knockdown of APPL1 or p38 MAPK inhibition blocked the expression of APN-induced calcification-related genes including ALP, Runt-related transcription factor 2 (RUNX2), and OCN. Furthermore, Alizarin Red staining of calcium nodes was not increased by the knockdown of APPL1 or p38 inhibition. Our data suggest that this regulation is mediated through the APPL1-p38 MAPK signaling pathway. These findings collectively provide evidence that APN induces the osteogenesis of h-JBMMSCs through APPL1-mediated p38 MAPK activation

  14. Stability after Cleft Maxillary Distraction Osteogenesis or Conventional Orthognathic Surgery

    Directory of Open Access Journals (Sweden)

    Kristian Andersen

    2015-06-01

    Full Text Available Objectives: To compare stability of maxillary advancements in patients with cleft lip and palate following distraction osteogenesis or orthognathic surgery. Material and Methods: Inclusion criteria: 1 cleft lip and palate, 2 advancement > 8 mm. Eleven patients comprised the distraction osteogenesis group (DOG. Seven patients comprised the orthognathic treatment group (CONVG. Skeletal and soft tissue points were traced on lateral cephalograms: T1 (preoperatively, T2 (after surgery, T3 (follow-up. Group differences were analyzed using Students t-test. Results: At T1-T2, advancement of 6.98 mm (P = 0.002 was observed in DOG. Horizontal overjet increased 11.62 mm (P = 0.001. A point-nasion-B point (ANB angle increased 8.82° (P = 0.001. Aesthetic plane to upper lip was reduced 5.44 mm (P = 0.017 and the naso-labial angle increased 16.6° (P = 0.001. Vertical overbite (VOB increased 2.27 mm (P = 0.021. In T2-T3, no significant changes were observed in DOG. In T1-T2, horizontal overjet increased 8.45 mm (P = 0.02. The ANB angle, 9.33° (P = 0.009 in CONVG. At T2-T3, VOB increased, 2.35 mm (P = 0.046, and the ANB angle reduced, 3.83° (P = 0.003. In T2-T3, no parameters changed in CONVG. At follow-up (T3, VOB increased in CONVG compared with DOG, (P = 0.01. Vertical position of A point differed between the groups (P = 0.04. No significant intergroup differences between soft tissue parameters occurred. Conclusions: Distraction osteogenesis resulted in a stable position of the maxilla and movement upwards in vertical plane, however in case of orthognathic treatment sagittal relapse and a continued postoperatively downward movement was registered.

  15. Osteogenic Matrix Cell Sheets Facilitate Osteogenesis in Irradiated Rat Bone

    Directory of Open Access Journals (Sweden)

    Yoshinobu Uchihara

    2015-01-01

    Full Text Available Reconstruction of large bone defects after resection of malignant musculoskeletal tumors is a significant challenge in orthopedic surgery. Extracorporeal autogenous irradiated bone grafting is a treatment option for bone reconstruction. However, nonunion often occurs because the osteogenic capacity is lost by irradiation. In the present study, we established an autogenous irradiated bone graft model in the rat femur to assess whether osteogenic matrix cell sheets improve osteogenesis of the irradiated bone. Osteogenic matrix cell sheets were prepared from bone marrow-derived stromal cells and co-transplanted with irradiated bone. X-ray images at 4 weeks after transplantation showed bridging callus formation around the irradiated bone. Micro-computed tomography images at 12 weeks postoperatively showed abundant callus formation in the whole circumference of the irradiated bone. Histology showed bone union between the irradiated bone and host femur. Mechanical testing showed that the failure force at the irradiated bone site was significantly higher than in the control group. Our study indicates that osteogenic matrix cell sheet transplantation might be a powerful method to facilitate osteogenesis in irradiated bones, which may become a treatment option for reconstruction of bone defects after resection of malignant musculoskeletal tumors.

  16. Miniature osmotic actuators for controlled maxillofacial distraction osteogenesis

    Science.gov (United States)

    Li, Yu-Hsien; Su, Yu-Chuan

    2010-06-01

    We have successfully demonstrated miniature actuators that are capable of converting chemical potential directly into steady mechanical movements for maxillofacial distraction osteogenesis. Pistons and diaphragms powered by osmosis are employed to provide the desired linear and volumetric displacements for bone distraction and potentially the release of bone morphogenetic proteins, respectively. The cylindrical-shaped miniature actuators are composed of polymeric materials and fabricated by molding and assembly processes. In the prototype demonstration, vapor-permeable thermoplastic polyurethane was employed as the semi-permeable material. 3 cm long actuators with piston and diaphragm radii of 1 mm and 500 µm, respectively, were fabricated and characterized. The maximum distraction force from the piston-type actuator is found to be 6 N while the piston travels at a constant velocity of 32 µm h-1 (or 0.77 mm/day) for about 1 week. Meanwhile, the release rate from the diaphragm-type actuator is measured to be constant, 0.15 µl h-1 (or 3.6 µl/day), throughout the experiment. Moreover, the sizes and output characteristics of the self-regulating actuators could readily be tailored to realize optimal distraction rate, rhythm and osteogenic activity. As such, the demonstrated miniature osmotic actuators could potentially serve as versatile apparatuses for maxillofacial distraction osteogenesis and fulfill the needs of a variety of implantable and biomedical applications.

  17. Glycosylation of Dentin Matrix Protein 1 is critical for osteogenesis.

    Science.gov (United States)

    Sun, Yao; Weng, Yuteng; Zhang, Chenyang; Liu, Yi; Kang, Chen; Liu, Zhongshuang; Jing, Bo; Zhang, Qi; Wang, Zuolin

    2015-12-04

    Proteoglycans play important roles in regulating osteogenesis. Dentin matrix protein 1 (DMP1) is a highly expressed bone extracellular matrix protein that regulates both bone development and phosphate metabolism. After glycosylation, an N-terminal fragment of DMP1 protein was identified as a new proteoglycan (DMP1-PG) in bone matrix. In vitro investigations showed that Ser(89) is the key glycosylation site in mouse DMP1. However, the specific role of DMP1 glycosylation is still not understood. In this study, a mutant DMP1 mouse model was developed in which the glycosylation site S(89) was substituted with G(89) (S89G-DMP1). The glycosylation level of DMP1 was down-regulated in the bone matrix of S89G-DMP1 mice. Compared with wild type mice, the long bones of S89G-DMP1 mice showed developmental changes, including the speed of bone remodeling and mineralization, the morphology and activities of osteocytes, and activities of both osteoblasts and osteoclasts. These findings indicate that glycosylation of DMP1 is a key posttranslational modification process during development and that DMP1-PG functions as an indispensable proteoglycan in osteogenesis.

  18. Osteogenesis and mineralization in a rabbit mandibular distraction osteogenesis model is promoted by the human LMP-1 gene.

    Science.gov (United States)

    Jiang, Xiaowen; Chen, Yanzhe; Fan, Xiaosheng; Zhang, Hao; Kun, Lu

    2015-04-01

    To observe the effects of LIM mineralization protein-1 (LMP-1) on bone regeneration in the distraction zone based on gene transduction, 36 New Zealand white rabbits underwent mandibular lengthening with a distraction rate of 2 mm/day. The animals were then randomly divided into group A and group B (n = 18, each). At the end of the distraction, Ad5-EGFP viruses and Ad5-LMP-1/EGFP viruses were injected into the distraction gaps in groups A and B, respectively. Seven days later, five randomly selected animals from each group were sacrificed to evaluate the survival of the virus. Four and 8 weeks after distraction osteogenesis (DO), six samples randomly selected from each group underwent CT scanning and dual energy X-ray absorptiometry detection. Eight weeks after DO, the rabbits were sacrificed, and the distracted mandibles were harvested. Six animals from each group processed for radiography, micro-CT, histology, and the rest samples were taken three-point bend testing. Using this model, better bone formation and mineralization in the distracted callus were observed in group B when compared with those in group A. The results suggest local transduction with LMP-1 gene promotes osteogenesis and mineralization in DO.

  19. Alveolar distraction osteogenesis applications in cleft lip and palate patients: a literature review

    Directory of Open Access Journals (Sweden)

    Öznur Mülayim

    2016-05-01

    Full Text Available Distraction osteogenesis technique has been successfully applied in the craniofacial area for long time, and it is being applied increasingly more in cleft lip and palate patients also. Especially in large cleft palate cases, bone grafting or surgical procedures such as distraction osteogenesis can be applied in order to ensure a smooth alveolar arc. In this literature review, alveolar (segmental distraction osteogenesis applications in patients with cleft lip and palate, indications of the technique, advantages and disadvantages, application methods and types of appliances used for this purpose have been evaluated. As conclusion, especially with the application of alveolar (segmental distraction osteogenesis, successful outcome can be achieved in cleft lip and palate patients with velopharyngeal insufficiency, maxillary hypoplasia and maxillary crowding, and this technique may be an alternative to conventional osteotomies and extraoral distractions.

  20. Vascular Development during Distraction Osteogenesis Proceeds by Sequential Intramuscular Arteriogenesis Followed by Intraosteal Angiogenesis

    OpenAIRE

    Morgan, Elise F.; Hussein, Amira I.; Al-Awadhi, Bader A.; Hogan, Daniel E.; Matsubara, Hidenori; Al-Alq, Zainab; Fitch, Jennifer; Andre, Billy; Hosur, Krutika; Gerstenfeld, Louis C.

    2012-01-01

    Vascular formation is intimately associated with bone formation during distraction osteogenesis (DO). While prior studies on this association have focused on vascular formation locally within the regenerate, we hypothesized that this vascular formation, as well as the resulting osteogenesis, rely heavily on the response of the vascular network in surrounding muscular compartments. To test this hypothesis, the spatiotemporal sequence of vascular formation was assessed in both muscular and osse...

  1. The potential roles of nanobiomaterials in distraction osteogenesis.

    Science.gov (United States)

    Makhdom, Asim M; Nayef, Lamees; Tabrizian, Maryam; Hamdy, Reggie C

    2015-01-01

    Distraction osteogenesis (DO) technique is used worldwide to treat many orthopedic conditions. Although successful, one limitation of this technique is the extended period of fixators until the bone is consolidated. The application of growth factors (GFs) is one promising approach to accelerate bone regeneration during DO. Despite promising in vivo results, its use is still limited in the clinic. This is secondary to inherent limitations of these GFs. Therefore, a development of delivery systems that allow sustained sequential release is necessary. Nanoparticles and nanocomposites have prevailing properties that can overcome the limitations of the current delivery systems. In addition, their use can overcome the current challenges associated with the insufficient mechanical properties of scaffolds and suboptimal osteogenic differentiation of transplanted cells in the distraction gap. We discuss the clinical implications, and potential early applications of the nanoparticles and nanocomposites for developing new treatments to accelerate bone regeneration in DO.

  2. An investigation on distraction osteogenesis in maxillofacial surgery

    Directory of Open Access Journals (Sweden)

    Fariaby J

    2003-08-01

    Full Text Available Distraction osteogenesis (DO, firstly introduced to the medical world by Russian scientist Ilizarov"nfor long bone lenghtening in orthopedics can be considered as an appropriate substitute in the treatment of"nmaxillofacial deformities. Natural events occuring during the repair of a fractured bone segment not only lead"nto the desired bone length but also prevent from the undesired disadvantages of osteotomies and bone"ngrafting. Recently a lot of investigations have been conducted to evaluate the efficacy of DO in the treatment"nof maxillofacial deformities, which in some cases have lead to successful results. In the present article a lot of"nissues in maxillofacial surgery and different treatment goals associated with DO are discussed.

  3. EXPRESSION OF ACTIVIN DURING THE MANDIBULAR DISTRACTION OSTEOGENESIS IN RABBIT

    Institute of Scientific and Technical Information of China (English)

    李昕; 祁佐良; 王炜; 董佳生; 林晓曦; 戴传昌

    2002-01-01

    Objective To investigate the role of activin on osteogenesis during mandibular distraction.Methods Rabbit mandibular distraction model was used and the new regenerating tissue in the distraction zone were harvested at different time points. lmmunohistochemical technique for activin A was performed in the harvested tissues. Results Positive stain was noted in early phases of distraction. At the end of distraction phase osteoblasts and osteoid in primary mineralization front were strongly stained and osteoblasts and osteocytes in peripheral new bone zone were moderately stained. There were also broad activin A stains in osteoblasts and active osteocytes in early consolidation phase. Conclusion The expression of activin is increased during mandibular distraction. It could play an important role in the process of osteoblastic cells secretion, differentiation to osteocytes and bone formation during mandibular distraction.

  4. The Regulation of Osteogenesis Using Electroactive Polypyrrole Films

    Directory of Open Access Journals (Sweden)

    Chuan Li

    2016-07-01

    Full Text Available To evaluate the effect of electrical conductivity of biomaterials on osteogenesis, polypyrrole (PPy was fabricated by oxidative chemical polymerization as substrates for cell culture. Through adjusting the concentrations of monomer and initiator, polypyrrole films with different electrical conductivities were fabricated. These fabricated polypyrrole films are transparent enough for easy optical microscopy. Fourier transform infrared spectroscopy, X-ray spectroscopy and four-point probe were used to assess the microstructures, surface chemical compositions and electrical sheet resistance of films, respectively. Results indicate that higher monomer and initiator concentration leads to highly-branched PPy chains and thus promotes the electron mobility and electrical conductivity. Selected polypyrrole films then were applied for culturing rat bone marrow stromal cells. Cell viability and mineralization assays reveal that not only these films are biocompatible, but also capable of enhancing the calcium deposition into the extra cellular matrix by the differentiated cells.

  5. The Molecular and Cellular Events That Take Place during Craniofacial Distraction Osteogenesis

    Directory of Open Access Journals (Sweden)

    Adi Rachmiel, DMD, PhD

    2014-01-01

    Full Text Available Summary: Gradual bone lengthening using distraction osteogenesis principles is the gold standard for the treatment of hypoplastic facial bones. However, the long treatment time is a major disadvantage of the lengthening procedures. The aim of this study is to review the current literature and summarize the cellular and molecular events occurring during membranous craniofacial distraction osteogenesis. Mechanical stimulation by distraction induces biological responses of skeletal regeneration that is accomplished by a cascade of biological processes that may include differentiation of pluripotential tissue, angiogenesis, osteogenesis, mineralization, and remodeling. There are complex interactions between bone-forming osteoblasts and other cells present within the bone microenvironment, particularly vascular endothelial cells that may be pivotal members of a complex interactive communication network in bone. Studies have implicated number of cytokines that are intimately involved in the regulation of bone synthesis and turnover. The gene regulation of numerous cytokines (transforming growth factor-β, bone morphogenetic proteins, insulin-like growth factor-1, and fibroblast growth factor-2 and extracellular matrix proteins (osteonectin, osteopontin during distraction osteogenesis has been best characterized and discussed. Understanding the biomolecular mechanisms that mediate membranous distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone regeneration that may lead to shorten the treatment duration.

  6. La unión craneocervical en el paciente con osteogénesis imperfecta

    OpenAIRE

    Ríos Ródenas, Mercedes

    2015-01-01

    La Osteogénesis Imperfecta (OI) es una enfermedad genética que se caracteriza por una reducción de la masa ósea con fragilidad ósea asociada. Los pacientes tienen tendencia a la fractura, por lo que también se la conoce como enfermedad de “huesos de cristal”. Por su baja incidencia, de 1:15.000 a 1:20.000 recién nacidos, está catalogada dentro del grupo de enfermedades raras. Estos pacientes, suelen presentar anomalías dentales y problemas oclusales severos que determinan que el odontólogo de...

  7. Dentinogenesis Imperfecta : A Family which was Affected for Over Three Generations.

    Science.gov (United States)

    Surendra, Poornima; Shah, Rohan; N M, Roshan; Reddy, V V Subba

    2013-08-01

    Dentinogenesis Imperfecta (DI) or hereditary opalescent dentin is inherited in a simple autosomal dominant mode with high penetrance and low mutation rates. It generally affects both the deciduous and the permanent dentitions. DI corresponds to a localized form of mesodermal dysplasia which is observed in the histo-differentiation. An early diagnosis and treatment are therefore fundamental, which aim at obtaining a favourable prognosis, since at late intervention makes the treatment more complex. We are presenting here a case of DI in which the disease affected the three generations of a family in India.

  8. Comparative study of dentinogenesis imperfecta in different families of the same topographical region.

    Science.gov (United States)

    Jindal, Mk; Maheshwari, Sandhya; Verma, Radhika; Khan, Mohd Toseef

    2009-09-01

    Dental hard tissue is subject to variety of disorders. Dentinogenesis Imperfecta is one such disorder attributed to heredity. It is known to be an autosomal dominant trait. Teeth with such 'imperfect' dentin are liable to be weak and discolored. The disease has variable penetration and therefore can be expressed as a range of phenotypic manifestations from mild discoloration and chipping to frank attrition and multiple pulp canal exposures. Here we present a comparative study of a series of cases from different families of one topographical region with widely different presentation and histories that are characteristic of this disease.

  9. An integrated treatment approach: a case report for dentinogenesis imperfecta type II.

    Science.gov (United States)

    Shetty, N; Joseph, M; Basnet, P; Dixit, S

    2007-01-01

    Dentinogenesis imperfecta type II or hereditary opalscent dentin is one of the most common autosomal dominant anomaly of dentin that occurs in both sex affecting approximately 1:8000 persons. Clinically this disorder is characterized by variable blue gray to yellow brown teeth, with fracture of enamel and excessive wear. The treatment strategy is focused towards protecting teeth from further wear and tear and total oral rehabilitation of patient with paramount importance to aesthetics, obtaining an appropriate vertical dimension and providing soft tissue support which will help to return the facial profile to a more normal appearance. A multidisciplinary treatment planning is required for treatment of these individuals.

  10. An Interdisciplinary Approach for Rehabilitating a Patient with Amelogenesis Imperfecta: A Case Report

    Directory of Open Access Journals (Sweden)

    Niloufar Khodaeian

    2012-01-01

    Full Text Available Amelogenesis imperfecta (AI has been defined as a group of hereditary enamel defects. It can be characterized by enamel hypoplasia, hypomaturation, or hypocalcification of the teeth. AI may be associated with some other dental and skeletal developmental defects. Restoration for patients with this condition should be oriented toward the functional and esthetic rehabilitation. This clinical report describes the oral rehabilitation of a young patient diagnosed with the hypoplastic type of AI in posterior teeth and hypomatured type of AI in anterior teeth.

  11. Amelogenesis Imperfecta and Generalized Gingival Overgrowth Resembling Hereditary Gingival Fibromatosis in Siblings: A Case Report

    Directory of Open Access Journals (Sweden)

    Emre Yaprak

    2012-01-01

    Full Text Available Amelogenesis imperfecta (AI is a group of hereditary disorders primarily characterized by developmental abnormalities in the quantity and/or quality of enamel. There are some reports suggesting an association between AI and generalized gingival enlargement. This paper describes the clinical findings and oral management of two siblings presenting both AI and hereditary gingival fibromatosis (HGF like generalized gingival enlargements. The treatment of gingival enlargements by periodontal flap surgery was successful in the management of the physiologic gingival form for both patients in the 3-year follow-up period. Prosthetic treatment was also satisfactory for the older patient both aesthetically and functionally.

  12. Noninvasive and Multidisciplinary Approach to the Functional and Esthetic Rehabilitation of Amelogenesis Imperfecta: A Pediatric Case Report

    OpenAIRE

    Juliana Feltrin de Souza; Camila Maria Bullio Fragelli; Marco Aurélio Benini Paschoal; Edson Alves de Campos; Leonardo Fernandes Cunha; Estela Maris Losso; Rita de Cássia Loiola Cordeiro

    2014-01-01

    Case Report. An 8-year-old girl with amelogenesis imperfecta (AI) reported unsatisfactory aesthetics, difficulty in mastication, and dental hypersensitivity. The intraoral examination observed mixed dentition, malocclusion in anteroposterior relationships, anterior open bite, and dental asymmetry. A hypoplastic form of AI was diagnosed in the permanent dentition. A multidisciplinary planning was performed and divided into preventive, orthopedic, and rehabilitation stages. Initially, preventiv...

  13. Scanning Еlectron Мicroscopy of Еnamel and Dentin of Тeeth with Hypocalcified Аmelogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Belcheva Ani B.

    2016-03-01

    Full Text Available The histological features of teeth with hypocalcified amelogenesis imperfecta (AI have been poorly studied, which calls into question the effectiveness of modern adhesive techniques used in the treatment of these noncarious defects.

  14. The absence of correlations between a clinical classification and ultrastructural findings in amelogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Baeckman, B.; Lundgren, T.; Engstroem, E.U.; Falk, L.K.L.; Chabala, J.M.; Levi-Setti, R.; Noren, J.G. (Dept. of Pedodontics, Univ. of Goeteborg (Sweden))

    1993-01-01

    This study was performed to examine whether a clinical classification of different phenotypes of amelogenesis imperfecta could be discernible at the ultrastructural level. 17 primary teeth from 16 children with hypomineralization, hypomaturation, or hypoplastic variants of the disease were collected for histologic studies of the enamel by means of polarized light microscopy, scanning electron microscopy (SEM), and secondary ion mass spectrometry (SIMS). Polarization microscopy showed that the enamel was hypomineralized; in 6 teeth a wavy configuration of the enamel prisms also appeared. Three histomorphologic main types could be discerned. In 10 of the teeth extensive hypermineralization of the bulk of the enamel was found. 1 tooth had an unusually tick enamel with only a thin normally mineralized surface layer. SIMS images showed less pronounced signals from Ca[sup 2+] and Na[sup +], but with stronger signals from Cl[sup -] and CN[sup -], representing the organic component of enamel. The SEM images showed an irregular prism pattern with marked interprismatic areas. Irrespective of the clinical appearance or the herediatary pattern the main findings were hypomineralized enamel with or without wavy bands. Neither of the analytical methods used in this paper distinguishes between the clinical phenotypes of amelogenesis imperfecta. 35 refs., 9 figs., 1 tab.

  15. Localization of a gene for autosomal dominant amelogenesis imperfecta (ADAI) to chromosome 4q

    Energy Technology Data Exchange (ETDEWEB)

    Forsman, K.; Lind. L.; Westermark, E. [Univ. of Umea (Sweden)] [and others

    1994-09-01

    Amelogenesis imperfecta (AI), a disorder affecting the formation of enamel, is significantly more common in Northern Sweden than in other parts of the world. The disease is genetically and clinically heterogenous, and autosomal dominant, autosomal recessive and X-linked inheritance patterns have been recognized. Linkage analysis has identified two different loci for X-linked AI, one of which is identical to the gene encoding the enamel protein amelogenin. However, in families with an autosomal inheritance pattern for AI, the genetic basis of the disease still remains unknown. We report a linkage analysis study performed on three Swedish families where the affected members had an autosomal dominant variant of AI (ADAI) clinically characterized as local hypoplastic. Significant linkage to microsatellite markers on chromosome 4q were obtained, with a maximum lod score of 5.55 for the marker D4S428. Recombinations in the family localized the ADAI locus to the interval between D4S392 and D4S395. This chromosome region contains both a locus for the dental disorder dentinogenesis imperfecta and the albumin gene. Serum albumin has been suggested to play a role in enamel formation, and the albumin gene is therefore a candidate gene for this genetic disease.

  16. Osteogenesis Capacity of a Novel BMP/α-TCP Bioactive Composite Bone Cement

    Institute of Scientific and Technical Information of China (English)

    YANG Wei-zhong; ZHOU Da-li; YIN Shao-ya; YIN Guang-fu; GAO Li-da; ZHANG Yun

    2004-01-01

    To improve the osteogenesis ability of α-tricalcium phosphate (α-TCP) bone cement,a novel BMP/α-TCP composite bone cement was prepared.By measuring the setting time and compressive strength,the hydration characteristic of bone cement was evaluated.Animal experiments including histological observation,radiographic investigation as well as digital image analyses reveal the difference of osteogenesis ability among BMP,α-TCP bone cement and BMP/α-TCP composite bone cement.Results show that α-TCP bone cement possesses excellent hydration and setting properties as well as high mechanical property.Comparison experiments show that BMP/α-TCP composite bone cement has a stronger osteogenesis ability.The gross observation of the implant site does not exhibit any inflammation or necrosis.Histological analyses reveal that the material has good osteointegration with host bone,and new bone formation is detected within the materials,which are degrading.Strong osteogenesis ability of the composite is due to not only the excellent osteoconductive potential but also the osteoinductive potential contributed by active BMP releasing and the material degradation.Large skull defect could be well-healed by filling BMP/α-TCP composite bone cement.This novel material proves itself to be an absorbable and bioactive bone cement with an osteogenesis ability.

  17. Visualization of vascular ultrastructure during osteogenesis by tissue engineering technique

    Institute of Scientific and Technical Information of China (English)

    ZHANG Kaigang; ZENG Bingfang; ZHANG Changqing

    2007-01-01

    The aim of this Paper was to observe and visualize the changes in osteoblasts by electron microscopy during osteogenesis using tissue engineering technique.We also studied the feasibility of improving tissue vascularization of the engineered bone by using small intestine submucosa (SIS)as the scaffold.Bone mesenchyrnal stem cells (BMSCs)were isolated by gradient centrifugation method.Bone mesenchymal stem cells were seeded in the SIS,and the scaffold-cell constructs were cultured in vitro for 2 weeks.Small intestine submucosa without BMSCs served as control.Both SIS scaffolds were then implanted subcutaneously in the dorsa of athymic mice.The implants were harvested after in vivo incubation for 4,8 and 12 weeks.The changes in osteoblasts and vascularization were observed under a transmission electron microscope and a scanning electron microscope.The BMSCs grew quite well,differentiating on the surface of the SIS and secreting a great deal of extracellular matrices.The scaffold-cell constructs formed a lot of bone and blood vessels in vivo.The scaffold degraded after 12 weeks.No osteoblasts,but vascularization and fibroblasts were observed,in the control.The SIS can be used as a scaffold for constructing tissue-engineered bone as it can improve the formation of bone and vessels in vivo.

  18. Potential Role of Activating Transcription Factor 5 during Osteogenesis

    Directory of Open Access Journals (Sweden)

    Luisa Vicari

    2016-01-01

    Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  19. Experimental model of distraction osteogenesis in edentulous rats

    Directory of Open Access Journals (Sweden)

    Maria Montserrat Pujadas Bigi

    2011-06-01

    Full Text Available Distraction osteogenesis (DO is a surgical technique producing bone lengthening by distraction of the fracture callus. Although a large number of experimental studies on the events associated with DO of craniofacial skeleton have been reported, the few employing rat mandibular bone DO used complicated designs and produced a small volume of newly formed bone. Thus, this study aims to present an original experimental model of mandibular DO in edentulous rats that produces a sufficient quantity and quality of intramembranous bone. Eight male Wistar rats, weighing 75 g, underwent extraction of lower molars. With rats weighing 350 g, right mandibular osteotomy was performed and the distraction device was placed. The distraction device was custom made using micro-implants, expansion screws, and acrylic resin. Study protocol: latency: 6 days, distraction: ¼ turn (0.175 mm once a day during 6 d, consolidation: 28 d after distraction phase, sacrifice. DO-treated and contralateral hemimandibles were dissected and compared macroscopically and using radiographic studies. Histological sections were obtained and stained with H&E. A distraction gap filled with newly formed and mature bone tissue was obtained. This model of mandibular DO proved useful to obtain adequate quantity and quality of bone to study bone regeneration.

  20. Hepcidin inhibition on the effect of osteogenesis in zebrafish.

    Science.gov (United States)

    Jiang, Yu; Yan, Yilin; Wang, Xiao; Zhu, Guoxing; Xu, You-Jia

    2016-07-15

    Iron overload, as a risk factor for osteoporosis, can result in the up-regulation of Hepcidin, and Hepcidin knockout mice display defects in their bone microarchitecture. However, the molecular and genetic mechanisms underlying Hepcidin deficiency-derived bone loss remain unclear. Here, we show that hepcidin knockdown in zebrafish using morpholinos leads to iron overload. Furthermore, a mineralization delay is observed in osteoblast cells in hepcidin morphants, and these defects could be partially restored with microinjection of hepcidin mRNA. Quantitative real-time PCR analyses revealed the osteoblast-specific genes alp, runx2a, runx2b, and sp7 in morphants are down-regulated. Furthermore, we confirmed qRT-PCR results by in situ hybridization and found down-regulated genes related to osteoblast function in hepcidin morphants. Most importantly, we revealed that hepcidin was capable of removing whole-body iron which facilitated larval recovery from the reductions in bone formation and osteogenesis induced by iron overload. PMID:27233600

  1. Early gene regulation of osteogenesis in embryonic stem cells

    KAUST Repository

    Kirkham, Glen R.

    2012-01-01

    The early gene regulatory networks (GRNs) that mediate stem cell differentiation are complex, and the underlying regulatory associations can be difficult to map accurately. In this study, the expression profiles of the genes Dlx5, Msx2 and Runx2 in mouse embryonic stem cells were monitored over a 48 hour period after exposure to the growth factors BMP2 and TGFβ1. Candidate GRNs of early osteogenesis were constructed based on published experimental findings and simulation results of Boolean and ordinary differential equation models were compared with our experimental data in order to test the validity of these models. Three gene regulatory networks were found to be consistent with the data, one of these networks exhibited sustained oscillation, a behaviour which is consistent with the general view of embryonic stem cell plasticity. The work cycle presented in this paper illustrates how mathematical modelling can be used to elucidate from gene expression profiles GRNs that are consistent with experimental data. © 2012 The Royal Society of Chemistry.

  2. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone

    Science.gov (United States)

    Adams, Ralf H.

    2016-01-01

    Summary The mammalian skeletal system harbours a hierarchical system of mesenchymal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in ageing organisms leading to loss of bone mass and increased fracture incidence. There is evidence indicating that the growth of blood vessels in bone and osteogenesis are coupled, but relatively little is known about the underlying cellular and molecular mechanisms. Here we identify a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties. These vessels are found in specific locations, mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors, and couple angiogenesis to osteogenesis. The abundance of these vessels and associated osteoprogenitors was strongly reduced in bone from aged animals, which was pharmacologically reversible to restore bone mass. PMID:24646994

  3. Distraction Osteogenesis of Multiple Ribs for the Treatment of Acquired Thoracic Dystrophy.

    Science.gov (United States)

    Piper, Merisa L; Delrosario, Lawrence; Hoffman, William Y

    2016-03-01

    Acquired thoracic dystrophy is a complication associated with early open repair of pectus excavatum resulting from extensive cartilage resection. The condition can cause serious functional and physiologic impairments, including cardiac compression and restrictive pulmonary function. We describe a 17-year-old boy with acquired thoracic dystrophy after Ravitch repair of pectus excavatum during infancy, whom we treated with distraction osteogenesis. The patient had a marked deformity of the chest wall and general hypoplasia of the central portion of the ribcage, with resultant symptomatic dyspnea on exertion and reduced pulmonary function. After osteotomies and distraction osteogenesis of bilateral ribs 4-8 using customized distraction devices, he had improved thoracic contour, resolution of dyspnea, and decreased restrictive pulmonary symptoms. This case suggests that distraction osteogenesis, already used extensively in craniomaxillofacial and orthopedic surgery, may be a novel method for management of this condition.

  4. Splicing site mutations in dentin sialophosphoprotein causing dentinogenesis imperfecta type II.

    Science.gov (United States)

    Holappa, Heidi; Nieminen, Pekka; Tolva, Liisa; Lukinmaa, Pirjo-Liisa; Alaluusua, Satu

    2006-10-01

    Dentinogenesis imperfecta (DGI) type II (OMIM # 125490) is an inherited disorder affecting dentin. Defective dentin formation results in discolored teeth that are prone to attrition and fracture. To date, several mutations have been described in the dentin sialophosphoprotein (DSPP) gene, causing DGI types II and III and dentin dysplasia type II. DSPP encodes two proteins: dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Here, we describe a mutational analysis of DSPP in seven Finnish families with DGI type II. We report two mutations and five single nucleotide polymorphisms. In one family we found a mutation that has been described earlier in families with different ethnicity, while in six families we found a novel g.1194C>A (IVS2-3) transversion. Bioinformatic analysis of known DSPP mutations suggests that DGI type II is usually caused by aberration of normal splicing.

  5. Phenotype characterization and DSPP mutational analysis of three Brazilian dentinogenesis imperfecta type II families.

    Science.gov (United States)

    Acevedo, A C; Santos, L J S; Paula, L M; Dong, J; MacDougall, M

    2009-01-01

    The aim of this study was to perform phenotype analysis and dentin sialophosphoprotein (DSPP) mutational analysis on 3 Brazilian families diagnosed with dentinogenesis imperfecta type II (DGI-II) attending the Dental Anomalies Clinic in Brasilia, Brazil. Physical and oral examinations, as well as radiographic and histopathological analyses, were performed on 28 affected and unaffected individuals. Clinical, radiographic and histopathological analyses confirmed the diagnosis of DGI-II in 19 individuals. Pulp stones were observed in ground sections of several teeth in 2 families, suggesting that obliteration of pulp chambers and root canals results from the growth of these nodular structures. Mutational DSPP gene analysis of representative affected family members revealed 7 various non-disease-causing alterations in exons 1-4 within the dentin sialoprotein domain. Further longitudinal studies are necessary to elucidate the progression of pulpal obliteration in the DGI-II patients studied as well as the molecular basis of their disease.

  6. Exclusion of known gene for enamel development in two Brazilian families with amelogenesis imperfecta.

    Science.gov (United States)

    Santos, Maria C L G; Hart, P Suzanne; Ramaswami, Mukundhan; Kanno, Cláudia M; Hart, Thomas C; Line, Sergio R P

    2007-01-31

    Amelogenesis imperfecta (AI) is a genetically heterogeneous group of diseases that result in defective development of tooth enamel. Mutations in several enamel proteins and proteinases have been associated with AI. The object of this study was to evaluate evidence of etiology for the six major candidate gene loci in two Brazilian families with AI. Genomic DNA was obtained from family members and all exons and exon-intron boundaries of the ENAM, AMBN, AMELX, MMP20, KLK4 and Amelotin gene were amplified and sequenced. Each family was also evaluated for linkage to chromosome regions known to contain genes important in enamel development. The present study indicates that the AI in these two families is not caused by any of the known loci for AI or any of the major candidate genes proposed in the literature. These findings indicate extensive genetic heterogeneity for non-syndromic AI.

  7. Exclusion of known gene for enamel development in two Brazilian families with amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Hart Thomas C

    2007-01-01

    Full Text Available Abstract Amelogenesis imperfecta (AI is a genetically heterogeneous group of diseases that result in defective development of tooth enamel. Mutations in several enamel proteins and proteinases have been associated with AI. The object of this study was to evaluate evidence of etiology for the six major candidate gene loci in two Brazilian families with AI. Genomic DNA was obtained from family members and all exons and exon-intron boundaries of the ENAM, AMBN, AMELX, MMP20, KLK4 and Amelotin gene were amplified and sequenced. Each family was also evaluated for linkage to chromosome regions known to contain genes important in enamel development. The present study indicates that the AI in these two families is not caused by any of the known loci for AI or any of the major candidate genes proposed in the literature. These findings indicate extensive genetic heterogeneity for non-syndromic AI.

  8. Satisfaction After Restoring Aesthetics and Function in a Child with Amelogenesis Imperfecta: A Case Report

    Directory of Open Access Journals (Sweden)

    Nihal Özcan

    2016-08-01

    Full Text Available Amelogenesis imperfecta (AI is a hereditary disorder that disrupts the formation of enamel in both primary and permanent dentition. Management of AI is a challenge for the patient and the clinician. This case report presents the management of AI in a six-year-old female patient. Considering the patient’s age, we decided to make removable dentures in order to avoid growth and development problems. Conventional complete dentures were made, vertical dimension was increased, and the desired aesthetics and function were gained. Additionally, satisfaction with prosthodontic rehabilitation was evaluated using a questionnaire. A high level of patient and parent satisfaction was obtained. Treatment planning for patients with AI is related to many factors including the age and socioeconomic status of the patient, the type and severity of the disorder, the intraoral situation at the time the treatment is planned and most importantly, cooperation of the patient plays a major role.

  9. Distraction Osteogenesis Enhances Remodeling of Remote Bones of the Skeleton: A Pilot Study

    OpenAIRE

    Funk, Julia F.; Krummrey, Gert; Perka, Carsten; Raschke, Michael J.; Bail, Hermann J.

    2009-01-01

    Bone injuries have a systemic influence on the remodeling of bone. This effect has not been examined concerning its extent and duration. We measured the systemic effect of distraction osteogenesis on the remodeling of bones of the axial skeleton by means of the mineral apposition rate and bone formation rate in an animal experiment. Distraction osteogenesis was performed on the tibiae of 24 mature Yucatan minipigs. After a 4-day latency period, the tibiae were distracted 2 mm/day for 10 days....

  10. Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Wang, Xin; Zhao, Yuming; Yang, Yuan; Qin, Man

    2015-01-01

    Amelogenesis imperfecta is a group of inherited diseases affecting the quality and quantity of dental enamel. To date, mutations in more than ten genes have been associated with non-syndromic amelogenesis imperfecta (AI). Among these, ENAM and LAMB3 mutations are known to be parts of the etiology of hypoplastic AI in human cases. When both alleles of LAMB3 are defective, it could cause junctional epidermolysis bullosa (JEB), while with only one mutant allele in the C-terminus of LAMB3, it could result in severe hypoplastic AI without skin fragility. We enrolled three Chinese families with hypoplastic autosomal-dominant AI. Despite the diagnosis falling into the same type, the characteristics of their enamel hypoplasia were different. Screening of ENAM and LAMB3 genes was performed by direct sequencing of genomic DNA from blood samples. Disease-causing mutations were identified and perfectly segregated with the enamel defects in three families: a 19-bp insertion mutation in the exon 7 of ENAM (c.406_407insTCAAAAAAGCCGACCACAA, p.K136Ifs*16) in Family 1, a single-base deletion mutation in the exon 5 of ENAM (c. 139delA, p. M47Cfs*11) in Family 2, and a LAMB3 nonsense mutation in the last exon (c.3466C>T, p.Q1156X) in Family 3. Our results suggest that heterozygous mutations in ENAM and LAMB3 genes can cause hypoplastic AI with markedly different phenotypes in Chinese patients. And these findings extend the mutation spectrum of both genes and can be used for mutation screening of AI in the Chinese population.

  11. Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Amelogenesis imperfecta is a group of inherited diseases affecting the quality and quantity of dental enamel. To date, mutations in more than ten genes have been associated with non-syndromic amelogenesis imperfecta (AI. Among these, ENAM and LAMB3 mutations are known to be parts of the etiology of hypoplastic AI in human cases. When both alleles of LAMB3 are defective, it could cause junctional epidermolysis bullosa (JEB, while with only one mutant allele in the C-terminus of LAMB3, it could result in severe hypoplastic AI without skin fragility. We enrolled three Chinese families with hypoplastic autosomal-dominant AI. Despite the diagnosis falling into the same type, the characteristics of their enamel hypoplasia were different. Screening of ENAM and LAMB3 genes was performed by direct sequencing of genomic DNA from blood samples. Disease-causing mutations were identified and perfectly segregated with the enamel defects in three families: a 19-bp insertion mutation in the exon 7 of ENAM (c.406_407insTCAAAAAAGCCGACCACAA, p.K136Ifs*16 in Family 1, a single-base deletion mutation in the exon 5 of ENAM (c. 139delA, p. M47Cfs*11 in Family 2, and a LAMB3 nonsense mutation in the last exon (c.3466C>T, p.Q1156X in Family 3. Our results suggest that heterozygous mutations in ENAM and LAMB3 genes can cause hypoplastic AI with markedly different phenotypes in Chinese patients. And these findings extend the mutation spectrum of both genes and can be used for mutation screening of AI in the Chinese population.

  12. Rehabilitation of a patient with amelogenesis imperfecta using porcelain veneers and CAD/CAM polymer restorations: A clinical report.

    Science.gov (United States)

    Saeidi Pour, Reza; Edelhoff, Daniel; Prandtner, Otto; Liebermann, Anja

    2015-01-01

    The complete dental rehabilitation of patients with a vertical dimension loss (VDL) caused by structural enamel deficits associated with amelogenesis imperfecta (AI) represents a difficult challenge for restorative teams. Accurate analysis and treatment planning that includes esthetic and functional evaluations and adequate material selection are important prerequisites for successful results. Long-term provisional restorations play an important role in exploring and elucidating the patients' esthetic demands and functional needs. Restorative treatment options can vary from requiring only oral hygiene instructions to extensive dental restorations that include composite fillings, ceramic veneers, metal-ceramic, or all-ceramic crowns. This case report describes a full-mouth rehabilitation of a patient with amelogenesis imperfecta including the case planning, bite replacement, preparation, and restoration setting steps with an experimental CAD/CAM polymer and porcelain veneers. PMID:26345104

  13. Treatment plan in amelogenesis imperfecta: A structured literature review on treatment protocols and dedicating the best possible options

    Directory of Open Access Journals (Sweden)

    Azari A.

    2008-12-01

    Full Text Available "nAmelogenesis imperfecta is an inherited disease that disturbs the formation of the enamel. It occurs as two main categories, hypomineralized and hypoplastic. Both deciduous and permanent teeth are affected, and the disorder may create unaesthetic appearance, dental sensitivity, and severe attrition. In this article through performing a structured literature review, numerous treatment modalities which so far advocated in rehabilitation of amelogenesis imperfecta in adults and children is discussed. The progressive changes on open bite, the problem of bonding during restorative phase of treatment , the rehabilitation difficulties of deciduous as well as permanent teeth is also discussed in detail and finally the interdisciplinary approach for treatment of this disability is demonstrated and some points for decision making in treatment protocols are suggested.

  14. Current practice of distraction osteogenesis for craniofacial anomalies in Europe: a web based survey.

    NARCIS (Netherlands)

    Nada, R.; Sugar, A.W.; Wijdeveld, M.G.M.M.; Borstlap, W.A.; Clauser, L.; Hoffmeister, B.; Kuijpers-Jagtman, A.M.

    2010-01-01

    Aim of the study was to get more insight into the opinion of European surgeons and orthodontists on the use of distraction osteogenesis (DO) for patients with different diagnoses and treatment protocols. A web based survey was set up, showing records of four patients with different conditions: hemif

  15. Craniofacial stability in patients with Crouzon or Apert syndrome after Le Fort III distraction osteogenesis

    NARCIS (Netherlands)

    J.H. Reitsma; E.M. Ongkosuwito; P.H. Buschang; L.N.A. van Adrichem; B. Prahl-Andersen

    2013-01-01

    Objective: Le Fort III osteotomy with distraction osteogenesis (DO) is used to improve the retruded midface in patients with Crouzon or Apert syndrome. This study aimed to evaluate sagittal and vertical preoperative and postoperative cephalometric changes of DO of the midface in patients with Crouzo

  16. Biodegradable Mg-Cu alloys with enhanced osteogenesis, angiogenesis, and long-lasting antibacterial effects.

    Science.gov (United States)

    Liu, Chen; Fu, Xuekun; Pan, Haobo; Wan, Peng; Wang, Lei; Tan, Lili; Wang, Kehong; Zhao, Ying; Yang, Ke; Chu, Paul K

    2016-06-07

    A series of biodegradable Mg-Cu alloys is designed to induce osteogenesis, stimulate angiogenesis, and provide long-lasting antibacterial performance at the same time. The Mg-Cu alloys with precipitated Mg2Cu intermetallic phases exhibit accelerated degradation in the physiological environment due to galvanic corrosion and the alkaline environment combined with Cu release endows the Mg-Cu alloys with prolonged antibacterial effects. In addition to no cytotoxicity towards HUVECs and MC3T3-E1 cells, the Mg-Cu alloys, particularly Mg-0.03Cu, enhance the cell viability, alkaline phosphatase activity, matrix mineralization, collagen secretion, osteogenesis-related gene and protein expressions of MC3T3-E1 cells, cell proliferation, migration, endothelial tubule forming, angiogenesis-related gene, and protein expressions of HUVECs compared to pure Mg. The favorable osteogenesis and angiogenesis are believed to arise from the release of bioactive Mg and Cu ions into the biological environment and the biodegradable Mg-Cu alloys with osteogenesis, angiogenesis, and long-term antibacterial ability are very promising in orthopedic applications.

  17. Rheological, biocompatibility and osteogenesis assessment of fish collagen scaffold for bone tissue engineering.

    Science.gov (United States)

    Elango, Jeevithan; Zhang, Jingyi; Bao, Bin; Palaniyandi, Krishnamoorthy; Wang, Shujun; Wenhui, Wu; Robinson, Jeya Shakila

    2016-10-01

    In the present investigation, an attempt was made to find an alternative to mammalian collagen with better osteogenesis ability. Three types of collagen scaffolds - collagen, collagen-chitosan (CCH), and collagen-hydroxyapatite (CHA) - were prepared from the cartilage of Blue shark and investigated for their physico-functional and mechanical properties in relation to biocompatibility and osteogenesis. CCH scaffold was superior with pH 4.5-4.9 and viscosity 9.7-10.9cP. Notably, addition of chitosan and HA (hydroxyapatite) improved the stiffness (11-23MPa) and degradation rate but lowered the water binding capacity and porosity of the scaffold. Interestingly, CCH scaffolds remained for 3days before complete in-vitro biodegradation. The decreased amount of viable T-cells and higher level of FAS/APO-1 were substantiated the biocompatibility properties of prepared collagen scaffolds. Osteogenesis study revealed that the addition of CH and HA in both fish and mammalian collagen scaffolds could efficiently promote osteoblast cell formation. The ALP activity was significantly high in CHA scaffold-treated osteoblast cells, which suggests an enhanced bone-healing process. Therefore, the present study concludes that the composite scaffolds prepared from fish collagen with higher stiffness, lower biodegradation rate, better biocompatible, and osteogenesis properties were suitable biomaterial for a bone tissue engineering application as an alternative to mammalian collagen scaffolds. PMID:27211297

  18. Intraoral distraction osteogenesis to lengthen the ascending ramus - Experience with seven patients

    NARCIS (Netherlands)

    Jansma, J; Bierman, MWJ; Becking, AG

    2004-01-01

    Seven children with facial asymmetry, mean age 12 years (range 11-14.5) were treated by intraoral distraction osteogenesis to lengthen the hypoplastic ramus. We achieved a mean increase in length of the ramus of 13 mm (range 10-16). In only one patient did we achieve a posterior open bite on the dis

  19. Craniofacial stability in patients with crouzon or apert syndrome after le fort III distraction osteogenesis

    NARCIS (Netherlands)

    J.H. Reitsma (Jacobus Harmen); E.M. Ongkosuwito (Edwin); P.H. Buschang (Peter); L.N.A. V Adrichem (Léon); B. Prahl-Andersen (Birte)

    2013-01-01

    textabstractObjective: Le Fort III osteotomy with distraction osteogenesis (DO) is used to improve the retruded midface in patients with Crouzon or Apert syndrome. This study aimed to evaluate sagittal and vertical preoperative and postoperative cephalometric changes of DO of the midface in patients

  20. Long term stability of mandibular advancement procedures : bilateral sagittal split osteotomy versus distraction osteogenesis

    NARCIS (Netherlands)

    Baas, E. M.; Pijpe, J.; de Lange, J.

    2012-01-01

    The aim of this study was to compare the postoperative stability of the mandible after a bilateral lengthening procedure, either by bilateral sagittal split osteotomy (BSSO) or distraction osteogenesis (DO). All patients who underwent mandibular advancement surgery between March 2001 and June 2004 w

  1. Oral and dental restoration of wide alveolar cleft using distraction osteogenesis and temporary anchorage devices.

    Science.gov (United States)

    Rachmiel, Adi; Emodi, Omri; Gutmacher, Zvi; Blumenfeld, Israel; Aizenbud, Dror

    2013-12-01

    Closure of large alveolar clefts and restoration by a fixed bridge supported by implants is a challenge in cleft alveolus treatment. A major aesthetic concern with distraction osteogenesis is obtaining a predictable position of the implant in relation to the newly generated bony alveolar ridge. We describe the treatment of a large cleft alveolus and palate reconstruction by distraction osteogenesis utilizing temporary anchorage devices (TADs) followed by a fixed implant-supported bridge. The method consists of segmental bone transport by distraction osteogenesis using a bone-borne distractor to minimize the alveolar cleft, followed by closure of the residual small defect by bone grafting three months later. During the active transport distraction, TADs were used exerting multidirectional forces to control the distraction vector forward and laterally for better interarch relation. A vertical alveolar distraction of the newly reconstructed bone of 15 mm facilitated optimal implant placement. The endosseous implants were osteointegrated and supported a fixed dental prosthesis. In conclusion, the large cleft alveolus defect was repaired in three dimensions by distraction osteogenesis assisted by TADs, and the soft tissues expanded simultaneously. Endosseous implants were introduced in the newly reconstructed bone for a fixed dental prosthesis enabling, rehabilitation of aesthetics, eating and speaking.

  2. The biology of distraction osteogenesis for correction of mandibular and craniomaxillofacial defects: A review

    Directory of Open Access Journals (Sweden)

    Subodh Shankar Natu

    2014-01-01

    The aim of this paper is to review the principle, technical considerations, applications and limitations of distraction osteogenesis. The application of osteodistraction offers novel solutions for surgical-orthodontic management of developmental anomalies of the craniofacial skeleton as bone may be molded into different shapes along with the soft tissue component gradually thereby resulting in less relapse.

  3. Craniofacial Distraction Osteogenesis: Effects of rhythm of distraction on bone regeneration

    NARCIS (Netherlands)

    U.M. Djasim (Urville)

    2008-01-01

    textabstractDistraction osteogenesis is defined as the formation of new bone tissue between bone segments that are divided by an osteotomy and then gradually separated by exerting an external force to the mobile bone segment(s). The resulting callus tissue in the distraction gap will eventually mine

  4. Stability of mandibular advancement procedures : Bilateral sagittal split osteotomy versus distraction osteogenesis

    NARCIS (Netherlands)

    Vos, M. D.; Baas, E. M.; de lange, J.; Bierenbroodspot, F.

    2009-01-01

    The aim of this study was to compare the postoperative stability of the mandible after a bilateral lengthening procedure, either by bilateral sagittal split osteotomy (BSSO) or distraction osteogenesis (DOG). All patients who underwent mandibular advancement surgery between March 2001 and June 2004

  5. Biodegradable Mg-Cu alloys with enhanced osteogenesis, angiogenesis, and long-lasting antibacterial effects

    Science.gov (United States)

    Liu, Chen; Fu, Xuekun; Pan, Haobo; Wan, Peng; Wang, Lei; Tan, Lili; Wang, Kehong; Zhao, Ying; Yang, Ke; Chu, Paul K.

    2016-01-01

    A series of biodegradable Mg-Cu alloys is designed to induce osteogenesis, stimulate angiogenesis, and provide long-lasting antibacterial performance at the same time. The Mg-Cu alloys with precipitated Mg2Cu intermetallic phases exhibit accelerated degradation in the physiological environment due to galvanic corrosion and the alkaline environment combined with Cu release endows the Mg-Cu alloys with prolonged antibacterial effects. In addition to no cytotoxicity towards HUVECs and MC3T3-E1 cells, the Mg-Cu alloys, particularly Mg-0.03Cu, enhance the cell viability, alkaline phosphatase activity, matrix mineralization, collagen secretion, osteogenesis-related gene and protein expressions of MC3T3-E1 cells, cell proliferation, migration, endothelial tubule forming, angiogenesis-related gene, and protein expressions of HUVECs compared to pure Mg. The favorable osteogenesis and angiogenesis are believed to arise from the release of bioactive Mg and Cu ions into the biological environment and the biodegradable Mg-Cu alloys with osteogenesis, angiogenesis, and long-term antibacterial ability are very promising in orthopedic applications. PMID:27271057

  6. Distraction osteogenesis as a treatment of obstructive sleep apnea syndrome

    Science.gov (United States)

    Tsui, Wai Kin; Yang, Yanqi; Cheung, Lim Kwong; Leung, Yiu Yan

    2016-01-01

    Abstract Background: To conduct a systematic review to answer the clinical question “What are the effectiveness of mandibular distraction osteogenesis (MDO) and its complications to treat patients with obstructive sleep apnea syndrome (OSAS)?”. Methods: A systematic search including a computer search with specific keywords, reference list search, and manual search were done. Relevant articles on MDO were assessed and selected in 3 rounds for final review based on 5 predefined inclusion criteria and followed by a round of critical appraisal. Different types of distraction and their treatment outcomes of OSAS were recorded with standardized form and analyzed. Results: Twelve articles were included in the final review. A total of 256 patients aged 7 days to 60 years were treated with either external or internal MDO, with a mean follow-up period of 6 to 37 months. The average distraction distance of 12 to 29 mm was achieved with various distraction protocols. The success rate for adult patients was 100%, and cure rates were ranged from 82% to 100%. The definition of success or cure for OSAS in children or infants was not defined. Therefore, there were no clearly reported success or cure rates for children/infants in the included studies. However, all studies reported that these patients showed significant improvement in OSAS, with many of them who avoided tracheostomy or had the tracheostomy decannulated. The complication rates were ranged from 0% to 21.4%, with most being from local wound infections or neurosensory disturbances. Conclusion: This systematic review showed that MDO was effective in resolving OSAS in adults with retrognathic mandible. MDO also showed promising results in infants or children with OSAS. From the results of this systematic review, we recommend to define the criteria of success or cure for OSAS surgery in children and infants. We also recommend setting up randomized controlled trials to compare MDO with traditional maxillomandibular

  7. The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible

    International Nuclear Information System (INIS)

    The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague–Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction

  8. The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible.

    Science.gov (United States)

    Monson, Laura A; Cavaliere, Christi M; Deshpande, Sagar S; Ayzengart, Alexander L; Buchman, Steven R

    2012-09-07

    The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague-Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction.

  9. The temporal expression of estrogen receptor alpha-36 and runx2 in human bone marrow derived stromal cells during osteogenesis

    International Nuclear Information System (INIS)

    Highlights: • ERα36 is the predominant ERα isoform involved in bone regulation in human BMSC. • ERα36 mRNA is significantly upregulated during the process of osteogenesis. • The pattern of ERα36 and runx2 mRNA expression is similar during osteogenesis. • ERα36 appears to be co-localised with runx2 during osteogenesis. - Abstract: During bone maintenance in vivo, estrogen signals through estrogen receptor (ER)-α. The objectives of this study were to investigate the temporal expression of ERα36 and ascertain its functional relevance during osteogenesis in human bone marrow derived stromal cells (BMSC). This was assessed in relation to runt-related transcription factor-2 (runx2), a main modulatory protein involved in bone formation. ERα36 and runx2 subcellular localisation was assessed using immunocytochemistry, and their mRNA expression levels by real time PCR throughout the process of osteogenesis. The osteogenically induced BMSCs demonstrated a rise in ERα36 mRNA during proliferation followed by a decline in expression at day 10, which represents a change in dynamics within the culture between the proliferative stage and the differentiative stage. The mRNA expression profile of runx2 mirrored that of ERα36 and showed a degree subcellular co-localisation with ERα36. This study suggests that ERα36 is involved in the process of osteogenesis in BMSCs, which has implications in estrogen deficient environments

  10. The temporal expression of estrogen receptor alpha-36 and runx2 in human bone marrow derived stromal cells during osteogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Francis, W.R., E-mail: w.francis@swansea.ac.uk [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Owens, S.E.; Wilde, C. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Pallister, I. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Trauma and Orthopaedics, Morriston Hospital, Swansea (United Kingdom); Kanamarlapudi, V. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Zou, W., E-mail: weizou60@hotmail.com [College of Life Sciences, Liaoning Normal University, Dalian 116081 (China); Liaoning Key Laboratories of Biotechnology and Molecular Drug Research and Development, Dalian 116081 (China); Xia, Z. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom)

    2014-10-24

    Highlights: • ERα36 is the predominant ERα isoform involved in bone regulation in human BMSC. • ERα36 mRNA is significantly upregulated during the process of osteogenesis. • The pattern of ERα36 and runx2 mRNA expression is similar during osteogenesis. • ERα36 appears to be co-localised with runx2 during osteogenesis. - Abstract: During bone maintenance in vivo, estrogen signals through estrogen receptor (ER)-α. The objectives of this study were to investigate the temporal expression of ERα36 and ascertain its functional relevance during osteogenesis in human bone marrow derived stromal cells (BMSC). This was assessed in relation to runt-related transcription factor-2 (runx2), a main modulatory protein involved in bone formation. ERα36 and runx2 subcellular localisation was assessed using immunocytochemistry, and their mRNA expression levels by real time PCR throughout the process of osteogenesis. The osteogenically induced BMSCs demonstrated a rise in ERα36 mRNA during proliferation followed by a decline in expression at day 10, which represents a change in dynamics within the culture between the proliferative stage and the differentiative stage. The mRNA expression profile of runx2 mirrored that of ERα36 and showed a degree subcellular co-localisation with ERα36. This study suggests that ERα36 is involved in the process of osteogenesis in BMSCs, which has implications in estrogen deficient environments.

  11. Disease: H00506 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available impairment also manifest in indivisuals with osteogenesis imperfecta. Mutations in the CRTAP, LEPRE1, and P...ption, gene) Michou L, Brown JP Genetics of bone diseases: Paget's disease, fibrous dysplasia, osteopetrosis, and osteogenesis

  12. Amelogenesis Imperfecta: Rehabilitation and Brainstorming on the Treatment Outcome after the First Year.

    Science.gov (United States)

    İzgi, Ayça Deniz; Kale, Ediz; Niğiz, Remzi

    2015-01-01

    Amelogenesis imperfecta (AI) affects enamel on primary and permanent dentition. This hereditary disorder is characterized by loss of enamel, poor esthetics, and hypersensitivity. Functional and cosmetic rehabilitation is challenging with variety of treatment options. This report presents the treatment of an AI patient using conventional fixed dentures and discusses issues related to posttreatment complications and prosthetic treatment outcome after 1 year of follow-up. A 19-year-old male AI patient with impaired self-esteem presented with hypersensitive, discolored, and mutilated teeth. Clinical examination revealed compromised occlusion and anterior open-bite. After hygiene maintenance full-coverage porcelain-fused-to-metal fixed restorations were indicated and applied. At the end of the treatment acceptable functional and esthetic results could be achieved. However, nearly a year after treatment a gingival inflammation in the esthetic zone complicated the outcome. Insufficient oral hygiene was to be blamed. Tooth sensitivity present from early childhood in these patients may prevent oral hygiene from becoming a habit. The relaxation due to relieve of hypersensitivity after treatment makes oral hygiene learning difficult. Continuous oral hygiene maintenance motivation may be crucial for the success of the treatment of AI patients. Treatment of AI patients should be carefully planned and an acceptable risk-benefit balance should be established.

  13. A novel DSPP mutation causes dentinogenesis imperfecta type II in a large Mongolian family

    Directory of Open Access Journals (Sweden)

    Chen Yujie

    2010-02-01

    Full Text Available Abstract Background Several studies have shown that the clinical phenotypes of dentinogenesis imperfecta type II (DGI-II may be caused by mutations in dentin sialophosphoprotein (DSPP. However, no previous studies have documented the clinical phenotype and genetic basis of DGI-II in a Mongolian family from China. Methods We identified a large five-generation Mongolian family from China with DGI-II, comprising 64 living family members of whom 22 were affected. Linkage analysis of five polymorphic markers flanking DSPP gene was used to genotype the families and to construct the haplotypes of these families. All five DSPP exons including the intron-exon boundaries were PCR-amplified and sequenced in 48 members of this large family. Results All affected individuals showed discoloration and severe attrition of their teeth, with obliterated pulp chambers and without progressive high frequency hearing loss or skeletal abnormalities. No recombination was found at five polymorphic markers flanking DSPP in the family. Direct DNA sequencing identified a novel A→G transition mutation adjacent to the donor splicing site within intron 3 in all affected individuals but not in the unaffected family members and 50 unrelated Mongolian individuals. Conclusion This study identified a novel mutation (IVS3+3A→G in DSPP, which caused DGI-II in a large Mongolian family. This expands the spectrum of mutations leading to DGI-II.

  14. A novel splicing mutation alters DSPP transcription and leads to dentinogenesis imperfecta type II.

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    Full Text Available Dentinogenesis imperfecta (DGI type II is an autosomal dominant disease characterized by a serious disorders in teeth. Mutations of dentin sialophosphoprotein (DSPP gene were revealed to be the causation of DGI type II (DGI-II. In this study, we identified a novel mutation (NG_011595.1:g.8662T>C, c.135+2T>C lying in the splice donor site of intron 3 of DSPP gene in a Chinese Han DGI-II pedigree. It was found in all affected subjects but not in unaffected ones or other unrelated healthy controls. The function of the mutant DSPP gene, which was predicted online and subsequently confirmed by in vitro splicing analysis, was the loss of splicing of intron 3, leading to the extended length of DSPP mRNA. For the first time, the functional non-splicing of intron was revealed in a novel DSPP mutation and was considered as the causation of DGI-II. It was also indicated that splicing was of key importance to the function of DSPP and this splice donor site might be a sensitive mutation hot spot. Our findings combined with other reports would facilitate the genetic diagnosis of DGI-II, shed light on its gene therapy and help to finally conquer human diseases.

  15. Phenotypic variation in dentinogenesis imperfecta/dentin dysplasia linked to 4q21.

    Science.gov (United States)

    Beattie, M L; Kim, J-W; Gong, S-G; Murdoch-Kinch, C A; Simmer, J P; Hu, J C-C

    2006-04-01

    Dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) are allelic disorders that primarily affect the formation of tooth dentin. Both conditions are autosomal-dominant and can be caused by mutations in the dentin sialophosphoprotein gene (DSPP, 4q21.3). We recruited 23 members of a four-generation kindred, including ten persons with dentin defects, and tested the hypothesis that these defects are linked to DSPP. The primary dentition showed amber discoloration, pulp obliteration, and severe attrition. The secondary dentition showed either pulp obliteration with bulbous crowns and gray discoloration or thistle-tube pulp configurations, normal crowns, and mild gray discoloration. Haplotype analyses showed no recombination between three 4q21-q24 markers and the disease locus. Mutational analyses identified no coding or intron junction sequence variations associated with affection status in DMP1, MEPE, or the DSP portion of DSPP. The defects in the permanent dentition were typically mild and consistent with a diagnosis of DD-II, but some dental features associated with DGI-II were also present. We conclude that DD-II and DGI-II are milder and more severe forms, respectively, of the same disease.

  16. Clinical, histopathologic, and genetic investigation in two large families with dentinogenesis imperfecta type II.

    Science.gov (United States)

    Malmgren, B; Lindskog, S; Elgadi, A; Norgren, S

    2004-04-01

    Dentinogenesis imperfecta (DI) type II, an inherited disorder affecting dentin, has been linked to mutations in the dentin sialophosphoprotein ( DSPP) gene on chromosome 4q21. The gene product is cleaved into two dentin-specific matrix proteins, dentin sialoprotein (DSP) and dentin phosphoprotein. The aim of this investigation was to study genotypes and phenotypes in two affected families with special reference to clinical, radiographic, and histopathologic manifestations. Seven affected members of Family A and five of Family B were documented clinically and radiographically; 14 and 10 teeth, respectively, were available for histopathologic investigation and prepared for ground sections, which were assessed semiquantitatively for dysplastic manifestations in the dentin according to the scoring system, dysplastic dentin score (DDS). Venous blood samples were collected from six affected and ten unaffected members of Family A, and from eight affected and six unaffected members of Family B. Genomic DNA was extracted and used for sequence analyses. The two families presented with different missense mutations. An Arg68Trp missense mutation in the DSP part of the gene was revealed in all six analyzed affected individuals in Family A. This mutation was not present in any of the ten healthy members. In Family B, an Ala15Val missense mutation involving the last residue of the signal peptide was found in all eight affected but in none of the six healthy members. The clinical and radiographic disturbances and DDS were more severe in Family B. The data indicate the presence of a genotype-phenotype correlation in DI type II.

  17. A novel DSPP mutation is associated with type II dentinogenesis Imperfecta in a chinese family

    Directory of Open Access Journals (Sweden)

    Xu Chengqi

    2007-08-01

    Full Text Available Abstract Background Hereditary defects of tooth dentin are classified into two main groups: dentin dysplasia (DD (types I and II and dentinogenesis imperfecta (DGI (types I, II, and III. Type II DGI is one of the most common tooth defects with an autosomal dominant mode of inheritance. One disease-causing gene, the dentin sialophosphoprotein (DSPP gene, has been reported for type II DGI. Methods In this study, we characterized a four-generation Chinese family with type II DGI that consists of 18 living family members, including 8 affected individuals. Linkage analysis with polymorphic markers D4S1534 and D4S414 that span the DSPP gene showed that the family is linked to DSPP. All five exons and exon-intron boundaries of DSPP were sequenced in members of type II DGI family. Results Direct DNA sequence analysis identified a novel mutation (c.49C→T, p.Pro17Ser in exon 1 of the DSPP gene. The mutation spot, the Pro17 residue, is the second amino acid of the mature DSP protein, and highly conserved during evolution. The mutation was identified in all affected individuals, but not in normal family members and 100 controls. Conclusion These results suggest that mutation p.Pro17Ser causes type II DGI in the Chinese family. This study identifies a novel mutation in the DSPP gene, and expands the spectrum of mutations that cause DGI.

  18. A DSPP mutation causing dentinogenesis imperfecta and characterization of the mutational effect.

    Science.gov (United States)

    Lee, Sook-Kyung; Lee, Kyung-Eun; Song, Su Jeong; Hyun, Hong-Keun; Lee, Sang-Hoon; Kim, Jung-Wook

    2013-01-01

    Mutations in the DSPP gene have been identified in nonsyndromic hereditary dentin defects, but the genotype-phenotype correlations are not fully understood. Recently, it has been demonstrated that the mutations of DSPP affecting the IPV leader sequence result in mutant DSPP retention in rough endoplasmic reticulum (ER). In this study, we identified a Korean family with dentinogenesis imperfecta type III. To identify the disease causing mutation in this family, we performed mutational analysis based on candidate gene sequencing. Exons and exon-intron boundaries of DSPP gene were sequenced, and the effects of the identified mutation on the pre-mRNA splicing and protein secretion were investigated. Candidate gene sequencing revealed a mutation (c.50C > T, p.P17L) in exon 2 of the DSPP gene. The splicing assay showed that the mutation did not influence pre-mRNA splicing. However, the mutation interfered with protein secretion and resulted in the mutant protein remaining largely in the ER. These results suggest that the mutation affects ER-to-Golgi apparatus export and results in the reduction of secreted DSPP and ER overload. This may induce cell stress and damage processing and/or transport of dentin matrix proteins or other critical proteins.

  19. A novel splicing mutation alters DSPP transcription and leads to dentinogenesis imperfecta type II.

    Science.gov (United States)

    Zhang, Jun; Wang, Jiucun; Ma, Yanyun; Du, Wenqi; Zhao, Siyang; Zhang, Zuowei; Zhang, Xiaojiao; Liu, Yue; Xiao, Huasheng; Wang, Hongyan; Jin, Li; Liu, Jie

    2011-01-01

    Dentinogenesis imperfecta (DGI) type II is an autosomal dominant disease characterized by a serious disorders in teeth. Mutations of dentin sialophosphoprotein (DSPP) gene were revealed to be the causation of DGI type II (DGI-II). In this study, we identified a novel mutation (NG_011595.1:g.8662T>C, c.135+2T>C) lying in the splice donor site of intron 3 of DSPP gene in a Chinese Han DGI-II pedigree. It was found in all affected subjects but not in unaffected ones or other unrelated healthy controls. The function of the mutant DSPP gene, which was predicted online and subsequently confirmed by in vitro splicing analysis, was the loss of splicing of intron 3, leading to the extended length of DSPP mRNA. For the first time, the functional non-splicing of intron was revealed in a novel DSPP mutation and was considered as the causation of DGI-II. It was also indicated that splicing was of key importance to the function of DSPP and this splice donor site might be a sensitive mutation hot spot. Our findings combined with other reports would facilitate the genetic diagnosis of DGI-II, shed light on its gene therapy and help to finally conquer human diseases.

  20. Dentin phosphoprotein gene locus is not associated with dentinogenesis imperfecta types II and III

    Energy Technology Data Exchange (ETDEWEB)

    MacDougall, M.; Zeichner-David, M.; Davis, A.; Slavkin, H. (Univ. of Southern California, Los Angeles (United States)); Murray, J. (Univ. of Iowa, Iowa City (United States)); Crall, M. (Ohio State Univ., Columbus (United States))

    1992-01-01

    Dentinogenesis imperfecta (DGI) is an autosomal dominant inherited dental disease which affects dentin production and mineralization. Genetic linkage studies have been performed on several multigeneration informative kindreds. These studies determined linkage between DGI types II and III and group-specific component (vitamin D-binding protein). This gene locus has been localized to the long arm of human chromosome 4 in the region 4q11-q21. Although this disease has been mapped to chromosome 4, the defective gene product is yet to be determined. Biochemical studies have suggested abnormal levels of dentin phosphoprotein (DPP) associated with DGI type II. This highly acidic protein is the major noncollagenous component of dentin, being solely expressed by the ectomesenchymal derived odontoblast cells of the tooth. The purpose of the present study was to establish whether DPP is associated with DGI types II and III, by using molecular biology techniques. The results indicated that DPP is not localized to any region of human chromosome 4, thus suggesting that the DPP gene is not directly associated with DGI type II or DGI type III. The data do not exclude the possibility that other proteins associated with DPP posttranslational modifications might be responsible for this genetic disease.

  1. Dentin phosphoprotein compound mutation in dentin sialophosphoprotein causes dentinogenesis imperfecta type III.

    Science.gov (United States)

    Dong, Juan; Gu, TingTing; Jeffords, Leticia; MacDougall, Mary

    2005-01-30

    A rare compound mutation involving a 36 bp deletion and 18 bp insertion within exon 5 of the dentin sialophosphoprotein (DSPP) gene has been identified in a family with dentinogenesis imperfecta type III (DGI-III). The DSPP gene encodes two major tooth matrix proteins dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). DSPP mutations associated with DGI-III results in an in frame truncation of the serine aspartic acid triplet repeat found in DPP near the highly conserved carboxyl terminal region shortening the protein by six amino acids. Clinically this family presents with discolored amber opalescent teeth and severe attrition of the tooth structure. This study is the first report of a mutation within DPP associated with a genetic dentin disease. Our study indicates that DGI-III is allelic with some forms of DGI-II with and without progressive hearing loss and dentin dysplasia type II that have been shown to be caused by mutations within the DSP coding or signal peptide regions.

  2. Full-mouth rehabilitation for a patient with dentinogenesis imperfecta: a clinical report.

    Science.gov (United States)

    Bencharit, Sompop; Border, Michael B; Mack, C Russell; Byrd, Warren C; Wright, John T

    2014-10-01

    Dentinogenesis imperfecta (DI) is a genetic disorder affecting the structural integrity of the dentin that can result in weakened dentin. The affected teeth, especially posterior teeth, often need to be extracted due to severe wear or fracture. This frequently yields a loss of posterior occlusion and occlusal vertical dimension. Besides wear and fracture, anterior teeth often have an unesthetic appearance because of discoloration. Current treatments of choice, including composite bonding restorations and, more recently, all-ceramic restorations, are typically suggested to preserve the remaining teeth and tooth structure. However, there are a limited number of studies on dental implants in patients with DI. The effectiveness of dentin bonding and dental implants in patients with DI is not known. This clinical report describes a 32-year-old Asian woman with DI who underwent full-mouth rehabilitation. The posterior occlusion, mostly in the molar areas, was restored with dental implants and ceramometal restorations. The anterior teeth and premolars were restored with bonded lithium disilicate glass-ceramic pressed veneers and crowns made with computer-aided design/computer-aided manufacturing. This case demonstrates that restoring functional occlusion and esthetics for a patient with DI can be completed successfully using contemporary implant therapy and adhesive dentistry.

  3. Amelogenesis Imperfecta: Rehabilitation and Brainstorming on the Treatment Outcome after the First Year

    Science.gov (United States)

    İzgi, Ayça Deniz; Kale, Ediz; Niğiz, Remzi

    2015-01-01

    Amelogenesis imperfecta (AI) affects enamel on primary and permanent dentition. This hereditary disorder is characterized by loss of enamel, poor esthetics, and hypersensitivity. Functional and cosmetic rehabilitation is challenging with variety of treatment options. This report presents the treatment of an AI patient using conventional fixed dentures and discusses issues related to posttreatment complications and prosthetic treatment outcome after 1 year of follow-up. A 19-year-old male AI patient with impaired self-esteem presented with hypersensitive, discolored, and mutilated teeth. Clinical examination revealed compromised occlusion and anterior open-bite. After hygiene maintenance full-coverage porcelain-fused-to-metal fixed restorations were indicated and applied. At the end of the treatment acceptable functional and esthetic results could be achieved. However, nearly a year after treatment a gingival inflammation in the esthetic zone complicated the outcome. Insufficient oral hygiene was to be blamed. Tooth sensitivity present from early childhood in these patients may prevent oral hygiene from becoming a habit. The relaxation due to relieve of hypersensitivity after treatment makes oral hygiene learning difficult. Continuous oral hygiene maintenance motivation may be crucial for the success of the treatment of AI patients. Treatment of AI patients should be carefully planned and an acceptable risk-benefit balance should be established. PMID:26783475

  4. Typical Features of Amelogenesis Imperfecta in Two Patients with Bartter’s Syndrome

    Directory of Open Access Journals (Sweden)

    Hercílio Martelli-Júnior

    2012-12-01

    Full Text Available Background/Aims: Amelogenesis imperfecta (AI is due to many inherited defects of enamel formation that affect the quantity and quality of enamel, leading to delay in tooth eruption and cosmetic consequences. AI has been described in association with nephrocalcinosis, which is called the enamel-renal syndrome. The aim of this case report is to describe typical features of AI in 2 patients with Bartter’s syndrome (BS for the first time. Methods: -Eight patients with confirmed BS were systematically screened for dental abnormalities as part of protocol. Those with suggestive clinical features of AI were submitted to panoramic X-ray and decayed teeth were analyzed by scanning electron microscopy. Results: Typical features of AI were detected in 2 girls with BS. These 2 patients showed nephrocalcinosis, and diagnosis and adequate clinical control were delayed. Genetic analysis detected the mutation responsible for BS in 1 of these patients. In this case, BS was due to a homozygous mutation of exon 5 of the KCNJ1 gene resulting in a substitution of valine for alanine at the codon 214 (A214V. Conclusions: The finding of typical features of AI in BS might constitute preliminary evidence that abnormalities of the biomineralization process found in patients with renal tubular disorders might also affect calcium deposition in dental tissues.

  5. A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis imperfecta.

    Science.gov (United States)

    Poulter, James A; Brookes, Steven J; Shore, Roger C; Smith, Claire E L; Abi Farraj, Layal; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-04-15

    We identified a family in which pitted hypomineralized amelogenesis imperfecta (AI) with premature enamel failure segregated in an autosomal recessive fashion. Whole-exome sequencing revealed a missense mutation (c.586C>A, p.P196T) in the I-domain of integrin-β6 (ITGB6), which is consistently predicted to be pathogenic by all available programmes and is the only variant that segregates with the disease phenotype. Furthermore, a recent study revealed that mice lacking a functional allele of Itgb6 display a hypomaturation AI phenotype. Phenotypic characterization of affected human teeth in this study showed areas of abnormal prismatic organization, areas of low mineral density and severe abnormal surface pitting in the tooth's coronal portion. We suggest that the pathogenesis of this form of AI may be due to ineffective ligand binding of ITGB6 resulting in either compromised cell-matrix interaction or compromised ITGB6 activation of transforming growth factor-β (TGF-β) impacting indirectly on ameloblast-ameloblast interactions and proteolytic processing of extracellular matrix proteins via MMP20. This study adds to the list of genes mutated in AI and further highlights the importance of cell-matrix interactions during enamel formation.

  6. Amelogenesis Imperfecta: Rehabilitation and Brainstorming on the Treatment Outcome after the First Year

    Directory of Open Access Journals (Sweden)

    Ayça Deniz İzgi

    2015-01-01

    Full Text Available Amelogenesis imperfecta (AI affects enamel on primary and permanent dentition. This hereditary disorder is characterized by loss of enamel, poor esthetics, and hypersensitivity. Functional and cosmetic rehabilitation is challenging with variety of treatment options. This report presents the treatment of an AI patient using conventional fixed dentures and discusses issues related to posttreatment complications and prosthetic treatment outcome after 1 year of follow-up. A 19-year-old male AI patient with impaired self-esteem presented with hypersensitive, discolored, and mutilated teeth. Clinical examination revealed compromised occlusion and anterior open-bite. After hygiene maintenance full-coverage porcelain-fused-to-metal fixed restorations were indicated and applied. At the end of the treatment acceptable functional and esthetic results could be achieved. However, nearly a year after treatment a gingival inflammation in the esthetic zone complicated the outcome. Insufficient oral hygiene was to be blamed. Tooth sensitivity present from early childhood in these patients may prevent oral hygiene from becoming a habit. The relaxation due to relieve of hypersensitivity after treatment makes oral hygiene learning difficult. Continuous oral hygiene maintenance motivation may be crucial for the success of the treatment of AI patients. Treatment of AI patients should be carefully planned and an acceptable risk-benefit balance should be established.

  7. Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate.

    Science.gov (United States)

    Brookes, Steven J; Barron, Martin J; Boot-Handford, Ray; Kirkham, Jennifer; Dixon, Michael J

    2014-05-01

    Inherited diseases caused by genetic mutations can arise due to loss of protein function. Alternatively, mutated proteins may mis-fold, impairing endoplasmic reticulum (ER) trafficking, causing ER stress and triggering the unfolded protein response (UPR). The UPR attempts to restore proteostasis but if unsuccessful drives affected cells towards apoptosis. Previously, we reported that in mice, the p.Tyr64His mutation in the enamel extracellular matrix (EEM) protein amelogenin disrupts the secretory pathway in the enamel-forming ameloblasts, resulting in eruption of malformed tooth enamel that phenocopies human amelogenesis imperfecta (AI). Defective amelogenin post-secretory self-assembly and processing within the developing EEM has been suggested to underlie the pathogenesis of X chromosome-linked AI. Here, we challenge this concept by showing that AI pathogenesis associated with the p.Tyr64His amelogenin mutation involves ameloblast apoptosis induced by ER stress. Furthermore, we show that 4-phenylbutyrate can rescue the enamel phenotype in affected female mice by promoting cell survival over apoptosis such that they are able to complete enamel formation despite the presence of the mutation, offering a potential therapeutic option for patients with this form of AI and emphasizing the importance of ER stress in the pathogenesis of this inherited conformational disease.

  8. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Maria Carolina Salomé Marquezin

    2015-01-01

    Full Text Available The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child’s psychosocial development.

  9. Simple recessive mutation in ENAM is associated with amelogenesis imperfecta in Italian Greyhounds.

    Science.gov (United States)

    Gandolfi, Barbara; Liu, Hongwei; Griffioen, Layle; Pedersen, Niels C

    2013-08-01

    We report a familial enamel hypoplasia in Italian Greyhounds resembling non-syndromic autosomal recessive amelogenesis imperfecta (AI) of humans. The condition uniformly affects deciduous and permanent teeth and is manifested by enamel roughening/thinning and brownish mottling. Affected teeth are often small and pointed with increased gaps. However, basic tooth structure is usually maintained throughout life, and fractures and dental cavities are not a serious problem as in humans. No tissues or organs other than teeth were affected by this mutation, and there was no relationship between enamel hypoplasia and either autoimmunity or periodontal disease, which also are prevalent in the breed. The enamel hypoplasia was associated with a 5-bp deletion in exon 10 of the enamelin (ENAM) gene. The prevalence of the enamel defect in Italian Greyhounds was 14%, and 30% of dogs with normal teeth were carriers. Genome analyses suggest that the trait is under inadvertent positive selection. Based on the deletion detected in the ENAM gene, a genetic test was developed for identifying mutation carriers, which would enable breeders to manage the trait. PMID:23638899

  10. A DSPP Mutation Causing Dentinogenesis Imperfecta and Characterization of the Mutational Effect

    Directory of Open Access Journals (Sweden)

    Sook-Kyung Lee

    2013-01-01

    Full Text Available Mutations in the DSPP gene have been identified in nonsyndromic hereditary dentin defects, but the genotype-phenotype correlations are not fully understood. Recently, it has been demonstrated that the mutations of DSPP affecting the IPV leader sequence result in mutant DSPP retention in rough endoplasmic reticulum (ER. In this study, we identified a Korean family with dentinogenesis imperfecta type III. To identify the disease causing mutation in this family, we performed mutational analysis based on candidate gene sequencing. Exons and exon-intron boundaries of DSPP gene were sequenced, and the effects of the identified mutation on the pre-mRNA splicing and protein secretion were investigated. Candidate gene sequencing revealed a mutation (c.50C > T, p.P17L in exon 2 of the DSPP gene. The splicing assay showed that the mutation did not influence pre-mRNA splicing. However, the mutation interfered with protein secretion and resulted in the mutant protein remaining largely in the ER. These results suggest that the mutation affects ER-to-Golgi apparatus export and results in the reduction of secreted DSPP and ER overload. This may induce cell stress and damage processing and/or transport of dentin matrix proteins or other critical proteins.

  11. Amelogénesis imperfecta. Informe de tres casos en una familia en Cali, Colombia.

    Directory of Open Access Journals (Sweden)

    Jesús Alberto Calero

    2009-11-01

    Full Text Available La frecuencia de la amelogénesis imperfecta (AI varía en las diferentes poblaciones mundiales. En Colombia se desconoce la frecuencia de la afección. Este informe muestra la consanguinidad de tres pacientes con AI la madre de 36 años y dos hijos de 8 y 15 años de edad. Esta condición se halló presente en cuatro familiares más próximos a la madre, lo que corrobora la condición hereditaria que se transmite como un rasgo dominante. El tratamiento para estos pacientes al principio es preventivo, con controles periódicos en los que se tiene en cuenta el manejo adecuado de hábitos de higiene oral. Una dieta balanceada pobre en azucares y agentes cariogénicos y una periódica fluorización se constituyen en el mejor procedimiento con la intención de fortalecer el esmalte remanente. Luego, a estos enfermos se les debe rehabilitar para la estética y la función de sus dientes.

  12. Aesthetic and functional rehabilitation of the primary dentition affected by amelogenesis imperfecta.

    Science.gov (United States)

    Marquezin, Maria Carolina Salomé; Zancopé, Bruna Raquel; Pacheco, Larissa Ferreira; Gavião, Maria Beatriz Duarte; Pascon, Fernanda Miori

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child's psychosocial development. PMID:25705526

  13. Sympathetic denervation-induced MSC mobilization in distraction osteogenesis associates with inhibition of MSC migration and osteogenesis by norepinephrine/adrb3.

    Directory of Open Access Journals (Sweden)

    Zhaojie Du

    Full Text Available The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympathetic denervation can deplete norepinephrine (NE in distraction-induced bone callus, down-regulate β3-adrenergic receptor (adrb3 in bone marrow mesenchymal stem cells (MSCs, and promote MSC migration from perivascular regions to bone-forming units. An in vitro Transwell assay was here used to demonstrate that NE can inhibit stroma-derived factor-1 (SDF-1-induced MSC migration and expression of the migration-related gene matrix metalloproteinase-2 (MMP-2 and downregulate that of the anti-migration gene tissue inhibitor of metalloproteinase-3 (TIMP-3. Knockdown of adrb3 using siRNA abolishes inhibition of MSC migration. An in vitro osteogenic assay was used to show that NE can inhibit the formation of MSC bone nodules and expression of the osteogenic marker genes alkaline phosphatase (ALP, osteocalcin (OCN, and runt-related transcription factor-2 (RUNX2, but knockdown of adrb3 by siRNA can abolish such inhibition of the osteogenic differentiation of MSCs. It is here concluded that sympathetic denervation-induced MSC mobilization in rat mandibular distraction osteogenesis is associated with inhibition of MSC migration and osteogenic differentiation by NE/adrb3 in vitro. These findings may facilitate understanding of the relationship of MSC mobilization and sympathetic nervous system across a wide spectrum of tissue regeneration processes.

  14. Sympathetic denervation-induced MSC mobilization in distraction osteogenesis associates with inhibition of MSC migration and osteogenesis by norepinephrine/adrb3.

    Science.gov (United States)

    Du, Zhaojie; Wang, Lei; Zhao, Yinghua; Cao, Jian; Wang, Tao; Liu, Peng; Zhang, Yabo; Yang, Xinjie; Cheng, Xiaobing; Liu, Baolin; Lei, Delin

    2014-01-01

    The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympathetic denervation can deplete norepinephrine (NE) in distraction-induced bone callus, down-regulate β3-adrenergic receptor (adrb3) in bone marrow mesenchymal stem cells (MSCs), and promote MSC migration from perivascular regions to bone-forming units. An in vitro Transwell assay was here used to demonstrate that NE can inhibit stroma-derived factor-1 (SDF-1)-induced MSC migration and expression of the migration-related gene matrix metalloproteinase-2 (MMP-2) and downregulate that of the anti-migration gene tissue inhibitor of metalloproteinase-3 (TIMP-3). Knockdown of adrb3 using siRNA abolishes inhibition of MSC migration. An in vitro osteogenic assay was used to show that NE can inhibit the formation of MSC bone nodules and expression of the osteogenic marker genes alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor-2 (RUNX2), but knockdown of adrb3 by siRNA can abolish such inhibition of the osteogenic differentiation of MSCs. It is here concluded that sympathetic denervation-induced MSC mobilization in rat mandibular distraction osteogenesis is associated with inhibition of MSC migration and osteogenic differentiation by NE/adrb3 in vitro. These findings may facilitate understanding of the relationship of MSC mobilization and sympathetic nervous system across a wide spectrum of tissue regeneration processes. PMID:25144690

  15. La Justicia Procedimental Imperfecta de John Rawls, en la Conciencia Jurídica Material de Alf Ross

    OpenAIRE

    Gabriela González Gómez; María de Lourdes González Chávez

    2005-01-01

    La inacabada justicia procedimental imperfecta planteada por John Rawls sobre los jueces, puede proyectarse hacia la conciencia jurídica material de Alf Ross si tomamos en consideración al juez como institución y ciudadano cuando aplica la ley en la población que juzga. La teoría de la justicia de John Rawls sólo considera al juzgador como representante de una institución social como lo es el Poder Judicial, pero nosotros sostenemos que debe aplicársele también como ciudadano los principios d...

  16. Distraction Osteogenesis Correction of Mandibular Ramis Fracture Malunion in a Juvenile Mute Swan ( Cygnus olor ).

    Science.gov (United States)

    Calvo Carrasco, Daniel; Dutton, Thomas A G; Shimizu, Naomi; Sabater, Mikel; Forbes, Neil A

    2016-03-01

    A juvenile mute swan (Cygnus olor) was presented with right lateral deviation of the mandible. Radiographs demonstrated a healed fracture of the right mandibular ramis, which had compromised osteogenesis. A corrective osteotomy was performed and an osteogenic distractor was inserted over the lateral aspect of the right mandible. Dental acrylic implants were fixed to the rhinotheca to correct rotational alignment. A pharyngostomy tube was placed to facilitate administration of nutrition and medication. Postoperative images confirmed correct alignment of the mandible in relation to the maxilla. Implants were removed and postoperative complications were not reported. This is the first report of an osteogenic distractor used to correct mandibular deviation in an avian species. Distraction osteogenesis should be considered as a valid surgical option in juvenile or adult avian patients with pathologic bone shortening.

  17. Study on osteogenesis promoted by low sound pressure level infrasound in vivo and some underlying mechanisms.

    Science.gov (United States)

    Long, Hua; Zheng, Liheng; Gomes, Fernando Cardoso; Zhang, Jinhui; Mou, Xiang; Yuan, Hua

    2013-09-01

    To clarify the effects of low sound pressure level (LSPL) infrasound on local bone turnover and explore its underlying mechanisms, femoral defected rats were stabilized with a single-side external fixator. After exposure to LSPL infrasound for 30min twice everyday for 6 weeks, the pertinent features of bone healing were assessed by radiography, peripheral quantitative computerized tomography (pQCT), histology and immunofluorescence assay. Infrasound group showed a more consecutive and smoother process of fracture healing and modeling in radiographs and histomorphology. It also showed significantly higher average bone mineral content (BMC) and bone mineral density (BMD). Immunofluorescence showed increased expression of calcitonin gene related peptide (CGRP) and decreased Neuropeptide Y (NPY) innervation in microenvironment. The results suggested the osteogenesis promotion effects of LSPL infrasound in vivo. Neuro-osteogenic network in local microenvironment was probably one target mediating infrasonic osteogenesis, which might provide new strategy to accelerate bone healing and remodeling. PMID:23770453

  18. The relationship between revascularisation and osteogenesis in fresh or demineralised bone grafts

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Talsnes, O;

    2001-01-01

    .50, p = 0.001), no correlation could be demonstrated in demineralised grafts (r = 0.09, p = 0.6). The results may indicate differences in the mechanisms of vascularisation and osteogenesis in the grafts used fresh or after demineralization but are, at present, difficult to fully explain.......Bone formation generally depends on adequate blood flow. Failure of bone grafts has been attributed to delayed revascularisation of the graft. We compared the relationship between revascularisation and osteogenesis, evaluated as entrapment of (141)Ce-labelled microspheres and uptake of (85)Sr......, respectively, in fresh or demineralised syngeneic bone grafts 3 weeks after heterotopic implantation in rats. Whereas a moderately high linear correlation between (85)Sr and (141)Ce radioactivity was found both in the (intact) host iliac bone (r = 0.75, p = 0.0001) and implanted fresh syngeneic grafts (r = 0...

  19. Mineralized collagen scaffolds induce hMSC osteogenesis and matrix remodeling

    OpenAIRE

    Weisgerber, D.W.; Caliari, S.R.; Harley, B.A.C.

    2015-01-01

    Biomaterials for bone tissue engineering must be able to instruct cell behavior in the presence of the complex biophysical and biomolecular environments encountered in vivo. While soluble supplementation strategies have been identified to enhance osteogenesis, they are subject to significant diffusive loss in vivo or the need for frequent re-addition in vitro. This investigation therefore explored whether biophysical and biochemical properties of a mineralized collagen-GAG scaffold were suffi...

  20. Spatiotemporal Analyses of Osteogenesis and Angiogenesis via Intravital Imaging in Cranial Bone Defect Repair.

    Science.gov (United States)

    Huang, Chunlan; Ness, Vincent P; Yang, Xiaochuan; Chen, Hongli; Luo, Jiebo; Brown, Edward B; Zhang, Xinping

    2015-07-01

    Osteogenesis and angiogenesis are two integrated components in bone repair and regeneration. A deeper understanding of osteogenesis and angiogenesis has been hampered by technical difficulties of analyzing bone and neovasculature simultaneously in spatiotemporal scales and in 3D formats. To overcome these barriers, a cranial defect window chamber model was established that enabled high-resolution, longitudinal, and real-time tracking of angiogenesis and bone defect healing via multiphoton laser scanning microscopy (MPLSM). By simultaneously probing new bone matrix via second harmonic generation (SHG), neovascular networks via intravenous perfusion of fluorophore, and osteoblast differentiation via 2.3-kb collagen type I promoter-driven GFP (Col2.3GFP), we examined the morphogenetic sequence of cranial bone defect healing and further established the spatiotemporal analyses of osteogenesis and angiogenesis coupling in repair and regeneration. We showed that bone defect closure was initiated in the residual bone around the edge of the defect. The expansion and migration of osteoprogenitors into the bone defect occurred during the first 3 weeks of healing, coupled with vigorous microvessel angiogenesis at the leading edge of the defect. Subsequent bone repair was marked by matrix deposition and active vascular network remodeling within new bone. Implantation of bone marrow stromal cells (BMSCs) isolated from Col2.3GFP mice further showed that donor-dependent bone formation occurred rapidly within the first 3 weeks of implantation, in concert with early angiogenesis. The subsequent bone wound closure was largely host-dependent, associated with localized modest induction of angiogenesis. The establishment of a live imaging platform via cranial window provides a unique tool to understand osteogenesis and angiogenesis in repair and regeneration, enabling further elucidation of the spatiotemporal regulatory mechanisms of osteoprogenitor cell interactions with host bone

  1. An Update on Midface Advancement Using Le Fort II and III Distraction Osteogenesis.

    Science.gov (United States)

    Tahiri, Youssef; Taylor, Jesse

    2014-11-01

    Le Fort II and III distraction osteogenesis (DO) is a powerful tool in the craniofacial armamentarium that is most often employed to treat patients with craniofacial syndromes such as Crouzon, Apert, or Pfeiffer syndrome who present with midfacial retrusion, shallow orbits, exorbitism, malocclusion, obstructive sleep apnea and facial imbalance. In this article, the authors will provide the reader with an update on techniques for the treatment of various forms of midfacial retrusion. PMID:25383053

  2. Spatial and Temporal Localization of WNT Signaling Proteins in a Mouse Model of Distraction Osteogenesis

    OpenAIRE

    Kasaai, Bahar; Moffatt, Pierre; Al-Salmi, Loai; Lauzier, Dominique; Lessard, Lucie; Hamdy, Reggie C.

    2012-01-01

    While the surgical procedure of distraction osteogenesis (DO) is very successful in the treatment of orthopedic conditions, its major limitation of slow bone formation in the distracted gap has prompted numerous attempts to understand and accelerate this slow bone formation. Interestingly, WNT/FZD signaling has been identified as a critical pathway in mediating bone formation and regeneration but has not yet been studied in the context of DO. The objective of this study was to determine the s...

  3. Three-Dimensional Evaluation of Mandibular Bone Regenerated By Bone Transport Distraction Osteogenesis

    OpenAIRE

    Kontogiorgos, Elias; Elsalanty, Mohammed E.; Zapata, Uriel; Zakhary, Ibrahim; Nagy, William W; Dechow, Paul C.; Opperman, Lynne A.

    2011-01-01

    The purpose of this study was to evaluate the structure and material properties of native mandibular bone and those of early regenerate bone, produced by bone transport distraction osteogenesis. Ten adult foxhounds were divided into two groups of five animals each. In all animals, a 3- to 4-cm defect was created on one side of the mandible. A bone transport reconstruction plate, consisting of a reconstruction plate with an attached intraoral transport unit, was utilized to stabilize the mandi...

  4. Influence of gravitational therapy on reparative osteogenesis in patients with osteomyelitis of lower extremities

    OpenAIRE

    Kotelnikov G.P.; Sonis A.G.

    2010-01-01

    The article provides a comparative analysis of reparative osteogenesis in 105 patients with diffuse osteomyelitis of lower extremities, covering bone in diameter totally or subtotally. In complex treatment 51 patients have experienced gravitational therapy (study group), 54 patients have been treated by standard methods (control group). The study was conducted in clinics of Samara State Medical University. Gravitational therapy is a new noninvasive method of physiotherapy, first used in the t...

  5. Phage nanofibers induce vascularized osteogenesis in 3D printed bone scaffolds.

    Science.gov (United States)

    Wang, Jianglin; Yang, Mingying; Zhu, Ye; Wang, Lin; Tomsia, Antoni P; Mao, Chuanbin

    2014-08-01

    A virus-activated matrix is developed to overcome the challenge of forming vascularized bone tissue. It is generated by filling a 3D printed bioceramic scaffold with phage nanofibers displaying high-density RGD peptide. After it is seeded with mesenchymal stem cells (MSCs) and implanted into a bone defect, the phage nanofibers induce osteogenesis and angiogenesis by activating endothelialization and osteogenic differentiation of MSCs.

  6. Expression of FAM20C in the Osteogenesis and Odontogenesis of Mouse

    OpenAIRE

    Wang, Xiaofang; Hao, Jianjun; Xie, Yixia; Sun, Yao; Hernandez, Brianda; Yamoah, Albert K.; Prasad, Monica; Zhu, Qinglin; Feng, Jian Q.; Qin, Chunlin

    2010-01-01

    Mutations in FAM20C were recently identified as the cause of lethal osteosclerotic bone dysplasia, which highlighted the important role of this molecule in biomineralization. No systematic studies have been performed to evaluate the expression pattern of this relatively new molecule in the developmental processes of bone and tooth. In the present study, we analyzed in detail the expression profile of FAM20C during osteogenesis and odontogenesis using ISH and IHC approaches. The specimens anal...

  7. Anterior Segmental Distraction Osteogenesis in the Hypoplastic Cleft Maxilla: Report of five cases

    OpenAIRE

    Sruthi Rao (Janardhan); Kotrashetti, S. M.; J. B. Lingaraj; Pinto, P. X.; Keluskar, K. M.; Siddharth Jain; Piyush Sone; Santhosh Rao

    2013-01-01

    Orthognathic surgery and distraction osteogenesis play a prime role in the correction of maxillary hypoplasia in patients with cleft lip and palate (CLP). Advancement of the anterior maxilla alone without interfering with the velopharyngeal sphincter may be advantageous in cleft patients, who more commonly have speech deficits and dental crowding. We present a case series of anterior maxillary segmental distraction for maxillary hypoplasia in 5 CLP patients with a one-year follow-up. A custom...

  8. Craniofacial reconstruction by transport distraction osteogenesis: corticotomy versus osteotomy--an experimental study.

    Science.gov (United States)

    Kramer, Franz-Josef; Mueller, Michal; Rahmstorf, Meike; Swennen, Gwen; Dempf, Rupert; Schierle, Hannes

    2004-07-01

    Transport osteogenesis is a modified technique of callus distraction appropriate for the reconstruction of extended osseous defects of long or flat bones. The aim of this study was to determine the regenerative potential of this technique related to the degree of mobilization of the transport segment. In 10 adult sheep, critically sized defects of the calvaria were treated by gradual movement of a transport segment consisting of calvarial bone. The transport segments were either corticotomized (n = 5) or osteotomized (n = 5). The latency period was 5 days; the rate of distraction was 1 mm/d, extended for approximately 40 days. The consolidation period was 28 days. Specimens were investigated by conventional radiography, computed tomography scans, immunofluorescence, and histological examination. In both groups, transport osteogenesis resulted in a complete closure of the defect. The volume and thickness of newly formed bone at the defect site did not differ significantly between the groups, nor did the extent of vascularization. Bone formation and remodeling occurred during the entire period of distraction and consolidation. Osteotomized transport segments became smaller during distraction, whereas the volume of corticotomized segments remained relatively constant. In conclusion, transport osteogenesis resulted in reliable closure of extended skull defects in adult organisms; corticotomy and osteotomy of the transport segment led to a similar extent of bone formation. PMID:15213530

  9. [Fundamental study on effect of high-mineral drinking water for osteogenesis in calciprivia ovariectomized rats].

    Science.gov (United States)

    Ogata, Fumihiko; Nagai, Noriaki; Ito, Yoshimasa; Kawasaki, Naohito

    2014-01-01

    Since osteoporosis is a major public health problem in Japan, it is important to clarify the effect of high-mineral drinking water consumption on osteogenesis. Therefore, in this study, we investigated the relationship between high-mineral drinking water consumption and osteogenesis in ovariectomized rats that received a low-calcium diet and purified water (PW group) or a low-calcium diet and high-mineral drinking water (CR group). High-mineral drinking water affected the rats' body weight. After 3 months, the bone density of the CR group was higher than that of the PW group (pcalcium in the bones after 3 months. These results suggest that high-mineral drinking water contributes to the maintenance of bone density and not to the amount of calcium in bone. On the other hand, serum alkaline phosphatase levels in the PW group at 3 months were higher than those in the CR group, which indicates that the blood concentration of calcium in the CR group was maintained. Moreover, the amount of magnesium in the bones and the blood concentration of magnesium in the CR group after 3 months were higher than the corresponding values in the PW group. These results suggest that consumption of high-mineral drinking water could be beneficial for osteogenesis (i.e., for maintaining bone quantity).

  10. The biology of distraction osteogenesis for correction of mandibular and craniomaxillofacial defects: A review.

    Science.gov (United States)

    Natu, Subodh Shankar; Ali, Iqbal; Alam, Sarwar; Giri, Kolli Yada; Agarwal, Anshita; Kulkarni, Vrishali Ajit

    2014-01-01

    Limb lengthening by distraction osteogenesis was first described in 1905. The technique did not gain wide acceptance until Gavril Ilizarov identified the physiologic and mechanical factors governing successful regeneration of bone formation. Distraction osteogenesis is a new variation of more traditional orthognathic surgical procedure for the correction of dentofacial deformities. It is most commonly used for the correction of more severe deformities and syndromes of both the maxilla and the mandible and can also be used in children at ages previously untreatable. The basic technique includes surgical fracture of deformed bone, insertion of device, 5-7 days rest, and gradual separation of bony segments by subsequent activation at the rate of 1 mm per day, followed by an 8-12 weeks consolidation phase. This allows surgeons, the lengthening and reshaping of deformed bone. The aim of this paper is to review the principle, technical considerations, applications and limitations of distraction osteogenesis. The application of osteodistraction offers novel solutions for surgical-orthodontic management of developmental anomalies of the craniofacial skeleton as bone may be molded into different shapes along with the soft tissue component gradually thereby resulting in less relapse.

  11. Comprehensive Review of Adipose Stem Cells and Their Implication in Distraction Osteogenesis and Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Mina W. Morcos

    2015-01-01

    Full Text Available Bone is one of the most dynamic tissues in the human body that can heal following injury without leaving a scar. However, in instances of extensive bone loss, this intrinsic capacity of bone to heal may not be sufficient and external intervention becomes necessary. Several techniques are available to address this problem, including autogenous bone grafts and allografts. However, all these techniques have their own limitations. An alternative method is the technique of distraction osteogenesis, where gradual and controlled distraction of two bony segments after osteotomy leads to induction of new bone formation. Although distraction osteogenesis usually gives satisfactory results, its major limitation is the prolonged duration of time required before the external fixator is removed, which may lead to numerous complications. Numerous methods to accelerate bone formation in the context of distraction osteogenesis have been reported. A viable alternative to autogenous bone grafts for a source of osteogenic cells is mesenchymal stem cells from bone marrow. However, there are certain problems with bone marrow aspirate. Hence, scientists have investigated other sources for mesenchymal stem cells, specifically adipose tissue, which has been shown to be an excellent source of mesenchymal stem cells. In this paper, the potential use of adipose stem cells to stimulate bone formation is discussed.

  12. Complications of mandibular distraction osteogenesis for acquired deformities: a systematic review of the literature.

    Science.gov (United States)

    Verlinden, C R A; van de Vijfeijken, S E C M; Tuinzing, D B; Becking, A G; Swennen, G R J

    2015-08-01

    A systematic review on complications in all forms of mandibular distraction osteogenesis (MDO) for acquired deformities was performed. Search terms expressing distraction osteogenesis were used in 'AND' combination with search terms comprising 'mandible' and terms for complication, failure, and morbidity. A search using PubMed (National Library of Medicine, NCBI), EMBASE, and the Cochrane Controlled Trials Register yielded 644 articles published between 1966 and mid October 2013. Three hundred and twenty-one eligible articles were screened in detail. Complications related to MDO in acquired deformities were reported in 105 clinical articles, involving 1332 patients. Treatments included alveolar distraction osteogenesis (ADO), mandibular lengthening, DO in bone grafts, and bi-/trifocal transport disc DO (TDDO) for segmental mandibular defects. A high incidence of complications was seen in MDO for acquired deformities (ADO 44.4%; residual group 43.9%). An index for classifying complications in MDO, based on the impact and further treatment or final results, was used. In the ADO group, soft tissue complications (8.0%), insufficient vector control (7.6%), temporary inferior alveolar nerve (IAN) neurosensory disturbances (6.5%), device-related problems (3.5%), mandible fractures (2.8%), insufficient bone formation (2.5%), and fracture of the transport disc (1.3%) were seen. In the residual group, temporary IAN neurosensory disturbances (13.4%), minor infection (5.3%), DO failure (4.0%), and device-related problems (3.8%) were reported.

  13. Tracheostomy versus mandibular distraction osteogenesis in infants with Robin sequence: a comparative cost analysis.

    Science.gov (United States)

    Paes, Emma C; Fouché, James J; Muradin, Marvick S M; Speleman, Lucienne; Kon, Moshe; Breugem, Corstiaan C

    2014-03-01

    Many treatments have been described for infants with Robin sequence and severe respiratory distress, but there have not been many comparative studies of outcome and cost-effectiveness. The aim of this study was to compare the cost and complications of two common interventions - mandibular distraction osteogenesis and tracheostomy. Nine patients with isolated Robin sequence (mandibular distraction osteogenesis, n=5, and tracheostomy, n=4) were included in the analyses. Predetermined costs and complications were obtained retrospectively from medical records and by questionnaires to the parents over a 12-month period. Overall direct costs (admission to hospital, diagnostics, surgery, and homecare) were 3 times higher for tracheostomy (€105.523 compared with €33.482, p=0.02). Overall indirect costs (absence from work) were almost 5 times higher (€2.543 compared with €543, p=0.02). There was a threefold increase in overall total cost/patient (both direct and indirect) for tracheostomy (€108.057 compared with 34.016, p=0.02) and 4 times more complications were encountered. This study shows that mandibular distraction osteogenesis in infants diagnosed with Robin sequence costs significantly less and results in fewer complications than tracheostomy, and this contributes to our current knowledge about the ideal approach for infants with Robin sequence and might provide a basis for institutional protocols in the future.

  14. Effects of intermittent negative pressure on osteogenesis in human bone marrow-derived stroma cells

    Institute of Scientific and Technical Information of China (English)

    Zhi YANG; Miao LIU; Yin-gang ZHANG; Xiong GUO; Peng XU

    2009-01-01

    Objective: We investigated the effects of intermittent negative pressure on osteogenesis in human bone marrow-derived stroma cells (BMSCs) in vitro. Methods: BMSCs were isolated from adult marrow donated by a hip osteoarthritis patient with prosthetic replacement and cultured in vitro. The third passage cells were divided into negative pressure treatment group and control group. The treatment group was induced by negative pressure intermittently (pressure: 50 kPa, 30 rain/times, and twice daily). The control was cultured in conventional condition. The osteogenesis of BMSCs was examined by phase-contrast mi-croscopy, the determination of alkaline phosphatase (ALP) activities, and the immunohistochemistry of collagen type I. The mRNA expressions of osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL) in BMSCs were analyzed by real-time poly-merase chain reaction (PCR). Results: BMSCs showed a typical appearance of osteoblast after 2 weeks of induction by intermit-tent negative pressure, the activity of ALP increased significantly, and the expression of collagen type 1 was positive. In the treatment group, the mRNA expression of OPG increased significantly (P<0.05) and the mRNA expression of OPGL decreased significantly (P<0.05) after 2 weeks, compared with the control. Conclusion: Intermittent negative pressure could promote os-teogenesis in human BMSCs in vitro.

  15. Structurally-diverse, PPARγ-activating environmental toxicants induce adipogenesis and suppress osteogenesis in bone marrow mesenchymal stromal cells

    International Nuclear Information System (INIS)

    Environmental obesogens are a newly recognized category of endocrine disrupting chemicals that have been implicated in contributing to the rising rates of obesity in the United States. While obesity is typically regarded as an increase in visceral fat, adipocyte accumulation in the bone has been linked to increased fracture risk, lower bone density, and osteoporosis. Exposure to environmental toxicants that activate peroxisome proliferator activated receptor γ (PPARγ), a critical regulator of the balance of differentiation between adipogenesis and osteogenesis, may contribute to the increasing prevalence of osteoporosis. However, induction of adipogenesis and suppression of osteogenesis are separable activities of PPARγ, and ligands may selectively alter these activities. It currently is unknown whether suppression of osteogenesis is a common toxic endpoint of environmental PPARγ ligands. Using a primary mouse bone marrow culture model, we tested the hypothesis that environmental toxicants acting as PPARγ agonists divert the differentiation pathway of bone marrow-derived multipotent mesenchymal stromal cells towards adipogenesis and away from osteogenesis. The toxicants tested included the organotins tributyltin and triphenyltin, a ubiquitous phthalate metabolite (mono-(2-ethylhexyl) phthalate, MEHP), and two brominated flame retardants (tetrabromobisphenol-a, TBBPA, and mono-(2-ethylhexyl) tetrabromophthalate, METBP). All of the compounds activated PPARγ1 and 2. All compounds increased adipogenesis (lipid accumulation, Fabp4 expression) and suppressed osteogenesis (alkaline phosphatase activity, Osx expression) in mouse primary bone marrow cultures, but with different potencies and efficacies. Despite structural dissimilarities, there was a strong negative correlation between efficacies to induce adipogenesis and suppress osteogenesis, with the organotins being distinct in their exceptional ability to suppress osteogenesis. As human exposure to a mixture of

  16. Mechanical and Vascular Cues Synergistically Enhance Osteogenesis in Human Mesenchymal Stem Cells.

    Science.gov (United States)

    Steward, Andrew J; Cole, Jacqueline H; Ligler, Frances S; Loboa, Elizabeth G

    2016-08-01

    Development and maintenance of a vascular network are critical for bone growth and homeostasis; strategies that promote vascular function are critical for clinical success of tissue-engineered bone constructs. Co-culture of endothelial cells (ECs) with mesenchymal stem cells (MSCs) and exposure to 10% cyclic tensile strain have both been shown to regulate osteogenesis in isolation, but potential synergistic effects have yet to be explored. The objective of this study was to expose an MSC-EC co-culture to 10% cyclic tensile strain to examine the role of this mechanical stimulus on MSC-EC behavior. We hypothesized that paracrine signaling from ECs would stimulate osteogenesis of MSCs, and exposure to 10% cyclic tensile strain would enhance this anabolic signal. Human umbilical vein ECs and human bone marrow-derived MSCs were either monocultured or co-cultured at a 1:1 ratio in a mixed osteo/angiogenic medium, exposed to 10% cyclic tensile strain at 1 Hz for 4 h/day for 2 weeks, and biochemically and histologically analyzed for endothelial and osteogenic markers. While neither 10% cyclic tensile strain nor co-culture alone had a significant effect on osteogenesis, the concurrent application of strain to an MSC-EC co-culture resulted in a significant increase in calcium accretion and mineral deposition, suggesting that co-culture and strain synergistically enhance osteogenesis. Neither co-culture, 10% cyclic tensile strain, nor a combination of these stimuli affected endothelial markers, indicating that the endothelial phenotype remained stable, but unresponsive to the stimuli evaluated in this study. This study is the first to investigate the role of cyclic tensile strain on the complex interplay between ECs and MSCs in co-culture. The results of this study provide key insights into the synergistic effects of 10% cyclic tensile strain and co-culture on osteogenesis. Understanding mechanobiological factors affecting MSC-EC crosstalk will help enhance strategies for

  17. Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression

    Science.gov (United States)

    Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H.; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin

    2016-01-01

    Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components, and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic protein 4 (Bmp4) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2f/f;Bmp4f/fameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling. PMID:27146352

  18. Kallikrein 4 and amelogenesis imperfecta%激肽释放酶4与釉质发生不全

    Institute of Scientific and Technical Information of China (English)

    王光平; 李明霞; 刘建国

    2013-01-01

      激肽释放酶4(KLK4)在釉质发生的转换期和成熟早期大量表达,水解基质蛋白,降低牙釉蛋白与羟磷灰石的结合,促进釉质晶体的生长和矿化。如果其基因突变或缺失,将导致釉质发生不全。本文就KLK4的结构、KLK4的表达与生物学功能、 KLK4的调控因子、 KLK4与釉质发生不全等研究进展作一综述。%  Kallikrein 4(KLK4) is a protease expressed during the transition and maturation stages of dental enamel formation. KLK4 can degrade enamel proteins, reduce enamel proteins combination to hydroxyapatite, and promote the enamel crystals growth and mineralization. KLK4 mutations or defects cause hypomaturation amelogenesis im-perfecta. This article reviewed the structure, expression, functions, regulatory factors of KLK4 and its effect on amelogenesis imperfecta.

  19. Clinical and molecular analysis of the enamelin gene ENAM in Colombian families with autosomal dominant amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Sandra Gutiérrez

    2012-01-01

    Full Text Available In this study, we analyzed the phenotype, clinical characteristics and presence of mutations in the enamelin gene ENAM in five Colombian families with autosomal dominant amelogenesis imperfecta (ADAI. 22 individuals (15 affected and seven unaffected belonging to five Colombian families with ADAI and eight individuals (three affected and five unaffected belonging to three Colombian families with autosomal recessive amelogenesis imperfecta (ARAI that served as controls for molecular alterations and inheritance patterns were studied. Clinical, radiographic and genetic evaluations were done in all individuals. Eight exons and three intron-exon boundaries were sequenced for mutation analysis. Two of the five families with ADAI had the hypoplasic phenotype, two had the hypocalcified phenotype and one had the hypomaturative phenotype. Anterior open bite and mandibular retrognathism were the most frequent skeletal abnormalities in the families with ADAI. No mutations were found. These findings suggest that ADAI in these Colombian families was unrelated to previously described mutations in the ENAM gene. These results also indicate that other regions not included in this investigation, such as the promoter region, introns and other genes should be considered as potential ADAI candidates.

  20. A novel splice acceptor mutation in the DSPP gene causing dentinogenesis imperfecta type II.

    Science.gov (United States)

    Kim, J W; Nam, S H; Jang, K T; Lee, S H; Kim, C C; Hahn, S H; Hu, J C C; Simmer, J P

    2004-08-01

    The dentin sialophosphoprotein (DSPP) gene (4q21.3) encodes two major noncollagenous dentin matrix proteins: dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Defects in the human gene encoding DSPP cause inherited dentin defects, and these defects can be associated with bilateral progressive high-frequency sensorineural hearing loss. Clinically, five different patterns of inherited dentin defects are distinguished and are classified as dentinogenesis imperfecta (DGI) types I, II, and III, and dentin dysplasia types I and II. The genetic basis for this clinical heterogeneity is unknown. Among the 11 members recruited from the studied kindred, five were affected with autosomal dominant DGI type II. The mutation (g.1188C-->G, IVS2-3C-->G) lay in the third from the last nucleotide of intron 2 and changed its sequence from CAG to GAG. The mutation was correlated with the affection status and was absent in 104 unaffected individuals (208 alleles) with the same ethnic and geological background. The proband was in the primary dentition stage and presented with multiple pulp exposures. The occlusal surface of his dental enamel was generally abraded, and the dentin was heavily worn and uniformly shaded brown. The dental pulp chambers appeared originally to be within normal limits without any sign of obliteration, but over time (by age 4), the pulp chambers became partially or completely obliterated. The oldest affected member (age 59) showed mild hearing loss at high-frequency (8 kHz). Permanent dentition was severely affected in the adults, who had advanced dental attrition, premature loss of teeth, and extensive dental reconstruction.

  1. Intrafibrillar Mineral May be Absent in Dentinogenesis Imperfecta Type II (DI-II)

    Energy Technology Data Exchange (ETDEWEB)

    Pople, John A.

    2001-03-29

    High-resolution synchrotron radiation computed tomography (SRCT) and small angle x-ray scattering (SAXS) were performed on normal and dentinogenesis imperfecta type II (DI-II) teeth. Three normal and three DI-II human third molars were used in this study. The normal molars were unerupted and had intact enamel; donors were female and ranged in age from 18-21y. The DI-II specimens, which were also unerupted with intact enamel, came from a single female donor age 20y. SRCT showed that the mineral concentration was 33% lower on average in the DI-II dentin with respect to normal dentin. The SAXS spectra from normal dentin exhibited low-angle diffraction peaks at harmonics of 67.6 nm, consistent with nucleation and growth of the apatite phase within gaps in the collagen fibrils (intrafibrillar mineralization). In contrast, the low-angle peaks were almost nonexistent in the DI-II dentin. Crystallite thickness was independent of location in both DI-II and normal dentin, although the crystallites were significantly thicker in DI-II dentin (6.8 nm (s.d. = 0.5) vs 5.1 nm (s.d. = 0.6)). The shape factor of the crystallites, as determined by SAXS, showed a continuous progression in normal dentin from roughly one-dimensional (needle-like) near the pulp to two-dimensional (plate-like) near the dentin-enamel junction. The crystallites in DI-II dentin, on the other hand, remained needle-like throughout. The above observations are consistent with an absence of intrafibrillar mineral in DI-II dentin.

  2. Mutational hot spot in the DSPP gene causing dentinogenesis imperfecta type II.

    Science.gov (United States)

    Kim, Jung-Wook; Hu, Jan C-C; Lee, Jae-Il; Moon, Sung-Kwon; Kim, Young-Jae; Jang, Ki-Taeg; Lee, Sang-Hoon; Kim, Chong-Chul; Hahn, Se-Hyun; Simmer, James P

    2005-02-01

    The current system for the classification of hereditary defects of tooth dentin is based upon clinical and radiographic findings and consists of two types of dentin dysplasia (DD) and three types of dentinogenesis imperfecta (DGI). However, whether DGI type III should be considered a distinct phenotype or a variation of DGI type II is debatable. In the 30 years since the classification system was first proposed, significant advances have been made regarding the genetic etiologies of inherited dentin defects. DGI type II is recognized as an autosomal dominant disorder with almost complete penetrance and a low frequency of de novo mutations. We have identified a mutation (c.52G-->T, p.V18F) at the first nucleotide of exon 3 of the DSPP (dentin sialophosphoprotein) gene in a Korean family (de novo) and a Caucasian family. This mutation has previously been reported as causing DGI type II in a Chinese family. These findings suggest that this mutation site represents a mutational "hot spot" in the DSPP gene. The clinical and radiographic features of these two families include the classic phenotypes associated with both DGI type II and type III. Finding that a single mutation causes both phenotypic patterns strongly supports the conclusion that DGI type II and DGI type III are not separate diseases but rather the phenotypic variation of a single disease. We propose a modification of the current classification system such that the designation "hereditary opalescent dentin" or "DGI type II" should be used to describe both the DGI type II and type III phenotypes.

  3. ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta.

    Science.gov (United States)

    Wang, Shih-Kai; Choi, Murim; Richardson, Amelia S; Reid, Bryan M; Lin, Brent P; Wang, Susan J; Kim, Jung-Wook; Simmer, James P; Hu, Jan C-C

    2014-04-15

    Integrins are cell-surface adhesion receptors that bind to extracellular matrices (ECM) and mediate cell-ECM interactions. Some integrins are known to play critical roles in dental enamel formation. We recruited two Hispanic families with generalized hypoplastic amelogenesis imperfecta (AI). Analysis of whole-exome sequences identified three integrin beta 6 (ITGB6) mutations responsible for their enamel malformations. The female proband of Family 1 was a compound heterozygote with an ITGB6 transition mutation in Exon 4 (g.4545G > A c.427G > A p.Ala143Thr) and an ITGB6 transversion mutation in Exon 6 (g.27415T > A c.825T > A p.His275Gln). The male proband of Family 2 was homozygous for an ITGB6 transition mutation in Exon 11 (g.73664C > T c.1846C > T p.Arg616*) and hemizygous for a transition mutation in Exon 6 of Nance-Horan Syndrome (NHS Xp22.13; g.355444T > C c.1697T > C p.Met566Thr). These are the first disease-causing ITGB6 mutations to be reported. Immunohistochemistry of mouse mandibular incisors localized ITGB6 to the distal membrane of differentiating ameloblasts and pre-ameloblasts, and then ITGB6 appeared to be internalized by secretory stage ameloblasts. ITGB6 expression was strongest in the maturation stage and its localization was associated with ameloblast modulation. Our findings demonstrate that early and late amelogenesis depend upon cell-matrix interactions. Our approach (from knockout mouse phenotype to human disease) demonstrates the power of mouse reverse genetics in mutational analysis of human genetic disorders and attests to the need for a careful dental phenotyping in large-scale knockout mouse projects.

  4. Amelogenesis imperfecta in two families with defined AMELX deletions in ARHGAP6.

    Directory of Open Access Journals (Sweden)

    Jan C-C Hu

    Full Text Available Amelogenesis imperfecta (AI is a group of inherited conditions featuring isolated enamel malformations. About 5% of AI cases show an X-linked pattern of inheritance, which are caused by mutations in AMELX. In humans there are two, non-allelic amelogenin genes: AMELX (Xp22.3 and AMELY (Yp11.2. About 90% of amelogenin expression is from AMELX, which is nested within intron 1 of the gene encoding Rho GTPase activating protein 6 (ARHGAP6. We recruited two AI families and determined that their disease-causing mutations were partial deletions in ARHGAP6 that completely deleted AMELX. Affected males in both families had a distinctive enamel phenotype resembling "snow-capped" teeth. The 96,240 bp deletion in family 1 was confined to intron 1 of ARHGAP6 (g.302534_398773del96240, but removed alternative ARHGAP6 promoters 1c and 1d. Analyses of developing teeth in mice showed that ARHGAP6 is not expressed from these promoters in ameloblasts. The 52,654 bp deletion in family 2 (g.363924_416577del52654insA removed ARHGAP6 promoter 1d and exon 2, precluding normal expression of ARHGAP6. The male proband of family 2 had slightly thinner enamel with greater surface roughness, but exhibited the same pattern of enamel malformations characteristic of males in family 1, which themselves showed minor variations in their enamel phenotypes. We conclude that the enamel defects in both families were caused by amelogenin insufficiency, that deletion of AMELX results in males with a characteristic snow-capped enamel phenotype, and failed ARHGAP6 expression did not appreciably alter the severity of enamel defects when AMELX was absent.

  5. Mutations in the Beta Propeller WDR72 Cause Autosomal-Recessive Hypomaturation Amelogenesis Imperfecta

    Science.gov (United States)

    El-Sayed, Walid; Parry, David A.; Shore, Roger C.; Ahmed, Mushtaq; Jafri, Hussain; Rashid, Yasmin; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Kirkham, Jennifer; Inglehearn, Chris F.; Mighell, Alan J.

    2009-01-01

    Healthy dental enamel is the hardest and most highly mineralized human tissue. Though acellular, nonvital, and without capacity for turnover or repair, it can nevertheless last a lifetime. Amelogenesis imperfecta (AI) is a collective term for failure of normal enamel development, covering diverse clinical phenotypes that typically show Mendelian inheritance patterns. One subset, known as hypomaturation AI, is characterised by near-normal volumes of organic enamel matrix but with weak, creamy-brown opaque enamel that fails prematurely after tooth eruption. Mutations in genes critical to enamel matrix formation have been documented, but current understanding of other key events in enamel biomineralization is limited. We investigated autosomal-recessive hypomaturation AI in a consanguineous Pakistani family. A whole-genome SNP autozygosity screen identified a locus on chromosome 15q21.3. Sequencing candidate genes revealed a point mutation in the poorly characterized WDR72 gene. Screening of WDR72 in a panel of nine additional hypomaturation AI families revealed the same mutation in a second, apparently unrelated, Pakistani family and two further nonsense mutations in Omani families. Immunohistochemistry confirmed intracellular localization in maturation-stage ameloblasts. WDR72 function is unknown, but as a putative β propeller is expected to be a scaffold for protein-protein interactions. The nearest homolog, WDR7, is involved in vesicle mobilization and Ca2+-dependent exocytosis at synapses. Vesicle trafficking is important in maturation-stage ameloblasts with respect to secretion into immature enamel and removal of cleaved enamel matrix proteins via endocytosis. This raises the intriguing possibility that WDR72 is critical to ameloblast vesicle turnover during enamel maturation. PMID:19853237

  6. Ectopic osteogenesis and angiogenesis regulated by porous architecture of hydroxyapatite scaffolds with similar interconnecting structure in vivo

    Science.gov (United States)

    Li, Jinyu; Zhi, Wei; Xu, Taotao; Shi, Feng; Duan, Ke; Wang, Jianxin; Mu, Yandong; Weng, Jie

    2016-01-01

    The macro-pore sizes of porous scaffold play a key role for regulating ectopic osteogenesis and angiogenesis but many researches ignored the influence of interconnection between macro-pores with different sizes. In order to accurately reveal the relationship between ectopic osteogenesis and macro-pore sizes in dorsal muscle and abdominal cavities of dogs, hydroxyapatite (HA) scaffolds with three different macro-pore sizes of 500–650, 750–900 and 1100–1250 µm were prepared via sugar spheres-leaching process, which also had similar interconnecting structure determined by keeping the d/s ratio of interconnecting window diameter to macro-pore size constant. The permeability test showed that the seepage flow of fluid through the porous scaffolds increased with the increase of macro-pore sizes. The cell growth in three scaffolds was not affected by the macro-pore sizes. The in vivo ectopic implantation results indicated that the macro-pore sizes of HA scaffolds with the similar interconnecting structure have impact not only the speed of osteogenesis and angiogenesis but also the space distribution of newly formed bone. The scaffold with macro-pore sizes of 750–900 µm exhibited much faster angiogenesis and osteogenesis, and much more uniformly distribution of new bone than those with other macro-pore sizes. This work illustrates the importance of a suitable macro-pore sizes in HA scaffolds with the similar interconnecting structure which provides the environment for ectopic osteogenesis and angiogenesis.

  7. Sobrevida de uma haste intramedular extensível (HIMEX) no tratamento de crianças com ostegênese imperfeita Survival rates of the HIMEX extensible nail in the treatment of children with osteogenesis imperfecta

    OpenAIRE

    William Dias Belangero; Bruno Livani; Vera Maria Santoro Belangero

    2010-01-01

    OBJETIVO: avaliar o desempenho da haste extensível ancorada por ganchos (HIMEX) em deformidades da osteogênese imperfeita (OI). MÉTODOS: Todas as crianças operadas com HIMEX entre 1990 - 2004. Foi comparado o número de fraturas, reaparecimento de deformidades e capacidade de deambulação antes e após a HIMEX; incidência de migração e sobrevida da haste por curvas de sobrevivência. RESULTADOS: 14 pacientes (2 a 18 anos), oito do sexo feminino, incluindo 46 procedimentos, 39 primários e sete re-...

  8. Four patients with Sillence type I osteogenesis imperfecta and mild bone fragility, complicated by left ventricular cardiac valvular disease and cardiac tissue fragility caused by type I collagen mutations

    DEFF Research Database (Denmark)

    Vandersteen, Anthony M; Lund, Allan M; Ferguson, David J P;

    2014-01-01

    showed unusual histology and abnormal collagen fibril ultra-structure at electron microscopy. The combined clinical, surgical, histological, ultra-structural, and molecular genetic data suggest the type I collagen defect as contributory to cardiac valvular disease. The degree of tissue fragility...... experienced at cardiac surgery in these individuals, also reported in a small number of similar case reports, suggests that patients with OI type I need careful pre-operative assessment and consideration of the risks and benefits of cardiac surgery. © 2013 Wiley Periodicals, Inc....

  9. The Differential Expression of 14 Kinds of Long Non-coding RNAs in Osteogenesis Imperfect%成骨不全14种长链非编码RNA差异表达分析

    Institute of Scientific and Technical Information of China (English)

    滕元伟; 任秀智; 王延宙; 张宇昂; 韩振忠; 韩金祥; 鲁艳芹

    2016-01-01

    Objective To explore the differential expression of 14 kinds of long non?--coding RNAs in bone tissues derived from osteogenesis imperfecta patients.Methods RT-qPCR was performed to detect the expression level of 14 Kinds of lncRNAs including ATB, EBIC, HEIH, hLACR1, HOTAIR, PVT1, LET, Loc285194, SRHC, LSINCTS, Nbla10727, Nbla12061, PRNCR1 and UC.388 in bone tissues derive from osteogenesis imperfect (OI) patients who received corrective surgery. Bone tissues from developmental dysplasia of the hip (DDH) were used as control. REST-2009 was performed to analyze the results.Results The expression of PRNCR1 was signiifcantly down-regulated in OI bone tissues. There’s no differential expression was observed in other thirteen lncRNAs, though the expression of HEIH, hLACR1, Nbla10727, Nbla12061 and UC.388 were up-regulated and LSINCTS was down-regulated. The expression of ATB,EBIC, HOTAIR, PVT1, LET, Loc285194 and SRHC was less than 2-fold of DDH control.Conclusions Low expression of PRNCR1 was observed in bone tissue from OI patients. The functions of PRNCR1 in OI need further study.%目的:研究14种长链非编码RNA(Long non-coding RNA, lncRNA)在成骨不全骨组织中的表达。方法采用先天性骻关节脱位患者骨组织作为对照,应用RT-qPCR分析成骨不全骨组织中14种lncRNA(ATB、EBIC、HEIH、hLACR1、HOTAIR、PVT1、LET、Loc285194、SRHC、LSINCTS 、Nbla10727、Nbla12061、PRNCR1与UC.388)的表达,使用REST-2009软件进行数据统计分析。结果与对照组相比,14种lncRNA中仅PRNCR1表达下调并具有显著性差异;ATB、EBIC、HOTAIR、PVT1、LET、Loc285194、SRHC等7种lncRNA表达差异均小于2倍,LSINCTS表达下调,HEIH、hLACR1、Nbla10727、Nbla12061与UC.388等5种lncRNA表达上调,但均无统计学意义。结论 PRNCR1在成骨不全骨组织中低表达,其在成骨不全疾病的功能尚有待于进一步研究。

  10. 牙本质发育不全的硬组织研究与进展%Research and progress of dental hard tissues with dentinogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    张莹; 邹静; 杨燃

    2012-01-01

    背景:牙本质发育不全是一种牙本质发育异常的常染色体显性遗传病,目前的研究大多集中在致病基因和临床治疗上,硬组织方面的研究相对较少.目的:就牙本质发育不全的硬组织研究进展做一综述.方法:以"牙本质发育不全,表面形态,动物模型,釉牙本质界,牙本质小管"为关键词,应用计算机检索1999/2011 CNKI数据库、PubMed 数据库,OVID 数据库.结果与结论:多数学者研究发现牙本质发育不全的釉质结构正常,病变主要表现在釉牙本质界和牙本质.其釉牙本质界大多表现为直线型外观,牙本质结构紊乱,钙化不规则,牙本质小管数目减少,胶原纤维形态和排列异常.这些异常结构的成因尚不清楚,有待深入研究.%BACKGROUND: Dentinogenesis imperfecta is an autosomal dominant genetic disease with dysplastic dentin. Currently, moststudies on dentinogenesis imperfecta are focused on phenotype analysis and clinical therapy, while the reports on dental hardtissue of dentinogenesis imperfecta are rare.OBJECTIVE: To summarize the research progress of dental hard tissue with dentinogenesis imperfecta.METHODS: A computer-based online search of CNKI, PubMed and OVID databases was performed for related articles publishedbetween 1999 and 2011, with the key words of "dentinogenesis imperfecta, surface morphology, animal model, enamel dentinaljunction, dentinal tubule" in English and Chinese.RESULTS AND CONCLUSION: Most researchers recognize that the enamel of dentinogenesis imperfecta has normal structure.The lesions are located in enamel dentinal junction. The enamel dentinal junction represents a linear appearance. The dentinrepresents a structure disturbance with irregular calcification. The number of dentinal tubules reduces. The shape andarrangement of collagen fibers are abnormal. The reasons for the abnormal structures are not clear and need further research.

  11. Effects of hyperbaric oxygen treatment on healing of maxillary distraction osteogenesis in beagle dogs

    International Nuclear Information System (INIS)

    Distraction osteogenesis has been widely used even in the craniofacial region. A long fixation time during the consolidation period, however, is a major clinical disadvantage. Hyperbaric oxygen (HBO) has been used to improve healing in ischemic wounds. We have recently started applying hyperbaric oxygen to cleft palate patients after maxillary distraction, but there is little basic evidence. We hypothesized that hyperbaric oxygen would enhance the healing of distraction osteogenesis in the cleft palate model in dogs. A bony segment including a canine was transported proximally into an artificial bone defect in the left palate. Three dogs were treated with hyperbaric oxygen for 20 days just after the distraction and three other dogs underwent only the distraction process (control group). Blood flow of the canine pulp in the bone segment was monitored using a laser Doppler flowmeter throughout the experiment. All the dogs were sacrificed on day 100, and radiological analysis using peripheral quantitative CT and histomorphometric evaluations were performed. Blood flow in the HBO-treated group recovered to the original level about 30 days faster than in the control group (p<0.05). Cortical bone mineral density was significantly higher at the distraction site in the HBO-treated group than in the control group (p<0.05). The histomorphometric analysis revealed that the newly formed bone area was also larger in the HBO-treated group than in the control group (p<0.05). These results suggest that hyperbaric oxygen treatment could be useful for early removal of the distraction device in distraction osteogenesis. (author)

  12. Combined micro computed tomography and histology study of bone augmentation and distraction osteogenesis

    Science.gov (United States)

    Ilgenstein, Bernd; Deyhle, Hans; Jaquiery, Claude; Kunz, Christoph; Stalder, Anja; Stübinger, Stefan; Jundt, Gernot; Beckmann, Felix; Müller, Bert; Hieber, Simone E.

    2012-10-01

    Bone augmentation is a vital part of surgical interventions of the oral and maxillofacial area including dental implantology. Prior to implant placement, sufficient bone volume is needed to reduce the risk of peri-implantitis. While augmentation using harvested autologous bone is still considered as gold standard, many surgeons prefer bone substitutes to reduce operation time and to avoid donor site morbidity. To assess the osteogenic efficacy of commercially available augmentation materials we analyzed drill cores extracted before implant insertion. In younger patients, distraction osteogenesis is successfully applied to correct craniofacial deformities through targeted bone formation. To study the influence of mesenchymal stem cells on bone regeneration during distraction osteogenesis, human mesenchymal stem cells were injected into the distraction gap of nude rat mandibles immediately after osteotomy. The distraction was performed over eleven days to reach a distraction gap of 6 mm. Both the rat mandibles and the drill cores were scanned using synchrotron radiation-based micro computed tomography. The three-dimensional data were manually registered and compared with corresponding two-dimensional histological sections to assess bone regeneration and its morphology. The analysis of the rat mandibles indicates that bone formation is enhanced by mesenchymal stem cells injected before distraction. The bone substitutes yielded a wide range of bone volume and degree of resorption. The volume fraction of the newly formed bone was determined to 34.4% in the computed tomography dataset for the augmentation material Geistlich Bio-Oss®. The combination of computed tomography and histology allowed a complementary assessment for both bone augmentation and distraction osteogenesis.

  13. Corticotomy and compression osteogenesis in the posterior maxilla for treating severe anterior open bite.

    Science.gov (United States)

    Kanno, T; Mitsugi, M; Furuki, Y; Kozato, S; Ayasaka, N; Mori, H

    2007-04-01

    A new technique is described for outpatient treatment of anterior open bite. The compression osteogenesis method with a two-stage corticotomy was used in the posterior maxilla to treat a woman with severe anterior open bite. Three-week post-surgical compression using anchor plates and elastics repositioned the posterior maxillary bone/teeth segments by 7 mm to the ideal superior position. The patient had a stable skeletal position of the maxilla at 14-month follow-up with satisfactory results and no complications after orthodontic treatment. This technique appears to be an efficient option for treating patients with anterior open bite. PMID:17110086

  14. Effect of alpha-tocopherol on bone formation during distraction osteogenesis: a rabbit model

    OpenAIRE

    Kurklu, Mustafa; Yildiz, Cemil; Kose, Ozkan; Yurttas, Yuksel; Karacalioglu, Ozgur; Serdar, Muhittin; Deveci, Salih

    2011-01-01

    Purpose The purpose of this study was to evaluate the effects of alpha-tocopherol on distraction osteogenesis. Materials and methods Right tibias of 30 New Zealand white rabbits were distracted at a rate of 0.5 mm/day for 20 days with a circular external fixator. Experimental group rabbits (n = 15) were administered i.m. 20 mg/kg/day alpha-tocopherol for 30 days. Radiographic examinations were performed at the 20th, 30th and 40th days. Bone scintigraphy was performed at the 5th and 20th days....

  15. Bone grafting versus distraction osteogenesis in pre-implant surgery. Literature review

    Directory of Open Access Journals (Sweden)

    Fotios TZERMPOS

    2013-08-01

    Full Text Available Nowadays there is an increasing demand for implant-supported prosthetic rehabilitation of the edentulous ridges. However problems occur regarding adequate bone support for implants. Loss of alveolar bone may be gradual due to age resorption or due to previous local pathology. Alveolar bone augmentation may be achieved by using a variety of different techniques.The aim of the present paper is to compare two methods for bone augmentation: distraction osteogenesis and bone grafting. Advantages and disadvantages of each one are presented and discussed together with their ability to reconstruct the deficient edentulous ridges with ultimate purpose the placement of implants upported prostheses.

  16. External frame distraction osteogenesis of the midface in the cleft patient

    Directory of Open Access Journals (Sweden)

    Hussain Syed

    2009-10-01

    Full Text Available Distraction osteogenesis has established itself as an accepted form of treatment in the management of midface deficiency in cleft patients. However, it is well known that some amount of relapse is inevitable in patients who undergo this procedure. Like most surgical techniques, it has its specific indications, limitations, and complications. The problems are amplified in some patients because of severe fibrosis resulting from previous palate and lip operations. This article reviews treatment planning, pre- and postoperative orthodontic management, operative technique, and mechanics of distraction. It also discusses long-term changes following distraction and protocols to optimize the results and minimize complications.

  17. Experimental study of the effect of platelet-rich plasma on osteogenesis in rabbit

    Institute of Scientific and Technical Information of China (English)

    张长青; 袁霆; 曾炳芳

    2004-01-01

    @@ Platelet-rich plasma (PRP) is produced from a patient's own blood by centrifugation, and PRP contains several kinds of growth factors in high concentration such as platelet derived growth factor (PDGF), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), epidermal growth factor (EGF), and so on.1 These growth factors have proved to offer an improved quality and speed of healing for both hard and soft tissue.2 In this study, PRP compounded with porous bioceramic was used to repair a bone defect in rabbit radius. The radiographic and histological qualitative and quantitative observations were performed to evaluate osteogenesis.

  18. Study on Z-H/BMP Toughened Compound Artificial Bone and Its Osteogenesis

    Institute of Scientific and Technical Information of China (English)

    XU Wei-guo; CHEN An-min; SUN Shu-zhen

    2003-01-01

    The purpose of this study was to find a kind of new artificial bone for anterior spinal fusion.ZrO2 stabilized by Y2O3 ( Y- PSZ), porous hydroxyapatite ( HA ) and bone morphogenetic protein (BMP) were used to make artificial compound bone ( Y2O3 ) ZrO2 -HA/ BMP( Z-H/ BMP ) , whose function was tested, microstructure and mineralogic composition constitution were analysised by SEM and XRD , and the corresponding animal tests were porformed. Osteogenesis of the material was observed by eyes, histology and SEM. Experimental results show that the component and ossific activity of Z-H/BMP were satisfactory.

  19. Novel genetic linkage of rat Sp6 mutation to Amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Muto Taro

    2012-06-01

    Full Text Available Abstract Background Amelogenesis imperfecta (AI is an inherited disorder characterized by abnormal formation of tooth enamel. Although several genes responsible for AI have been reported, not all causative genes for human AI have been identified to date. AMI rat has been reported as an autosomal recessive mutant with hypoplastic AI isolated from a colony of stroke-prone spontaneously hypertensive rat strain, but the causative gene has not yet been clarified. Through a genetic screen, we identified the causative gene of autosomal recessive AI in AMI and analyzed its role in amelogenesis. Methods cDNA sequencing of possible AI-candidate genes so far identified using total RNA of day 6 AMI rat molars identified a novel responsible mutation in specificity protein 6 (Sp6. Genetic linkage analysis was performed between Sp6 and AI phenotype in AMI. To understand a role of SP6 in AI, we generated the transgenic rats harboring Sp6 transgene in AMI (Ami/Ami + Tg. Histological analyses were performed using the thin sections of control rats, AMI, and Ami/Ami + Tg incisors in maxillae, respectively. Results We found the novel genetic linkage between a 2-bp insertional mutation of Sp6 gene and the AI phenotype in AMI rats. The position of mutation was located in the coding region of Sp6, which caused frameshift mutation and disruption of the third zinc finger domain of SP6 with 11 cryptic amino acid residues and a stop codon. Transfection studies showed that the mutant protein can be translated and localized in the nucleus in the same manner as the wild-type SP6 protein. When we introduced the CMV promoter-driven wild-type Sp6 transgene into AMI rats, the SP6 protein was ectopically expressed in the maturation stage of ameloblasts associated with the extended maturation stage and the shortened reduced stage without any other phenotypical changes. Conclusion We propose the addition of Sp6 mutation as a new molecular diagnostic criterion for the

  20. Amelogenin signal peptide mutation: Correlation between mutations in the amelogenin gene (AMGX) and manifestations of X-linked amelogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Lagerstroem-Fermer, M.; Nilsson, M.; Pettersson, U. [Univ. of Uppsala (Sweden)] [and others

    1995-03-01

    Formation of tooth enamel is a poorly understood biological process. In this study the authors describe a 9-bp deletion in exon 2 of the amelogenin gene (AMGX) causing X-linked hypoplastic amelogenesis imperfecta, a disease characterized by defective enamel. The mutation results in the loss of 3 amino acids and exchange of 1 in the signal peptide of the amelogenin protein. This deletion in the signal peptide probably interferes with translocation of the amelogenin protein during synthesis, resulting in the thin enamel observed in affected members of the family. The authors compare this mutation to a previously reported mutation in the amelogenin gene that causes a different disease phenotype. The study illustrates that molecular analysis can help explain the various manifestations of a tooth disorder and thereby provide insights into the mechanisms of tooth enamel formation. 16 refs., 2 figs., 1 tab.

  1. Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta.

    Science.gov (United States)

    Huckert, Mathilde; Stoetzel, Corinne; Morkmued, Supawich; Laugel-Haushalter, Virginie; Geoffroy, Véronique; Muller, Jean; Clauss, François; Prasad, Megana K; Obry, Frédéric; Raymond, Jean Louis; Switala, Marzena; Alembik, Yves; Soskin, Sylvie; Mathieu, Eric; Hemmerlé, Joseph; Weickert, Jean-Luc; Dabovic, Branka Brukner; Rifkin, Daniel B; Dheedene, Annelies; Boudin, Eveline; Caluseriu, Oana; Cholette, Marie-Claude; Mcleod, Ross; Antequera, Reynaldo; Gellé, Marie-Paule; Coeuriot, Jean-Louis; Jacquelin, Louis-Frédéric; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Van Hul, Wim; Bertola, Debora; Dollé, Pascal; Verloes, Alain; Mortier, Geert; Dollfus, Hélène; Bloch-Zupan, Agnès

    2015-06-01

    Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder.

  2. Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta

    Science.gov (United States)

    Huckert, Mathilde; Stoetzel, Corinne; Morkmued, Supawich; Laugel-Haushalter, Virginie; Geoffroy, Véronique; Muller, Jean; Clauss, François; Prasad, Megana K.; Obry, Frédéric; Raymond, Jean Louis; Switala, Marzena; Alembik, Yves; Soskin, Sylvie; Mathieu, Eric; Hemmerlé, Joseph; Weickert, Jean-Luc; Dabovic, Branka Brukner; Rifkin, Daniel B.; Dheedene, Annelies; Boudin, Eveline; Caluseriu, Oana; Cholette, Marie-Claude; Mcleod, Ross; Antequera, Reynaldo; Gellé, Marie-Paule; Coeuriot, Jean-Louis; Jacquelin, Louis-Frédéric; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Van Hul, Wim; Bertola, Debora; Dollé, Pascal; Verloes, Alain; Mortier, Geert; Dollfus, Hélène; Bloch-Zupan, Agnès

    2015-01-01

    Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder. PMID:25669657

  3. Loss of epithelial FAM20A in mice causes amelogenesis imperfecta, tooth eruption delay and gingival overgrowth

    Science.gov (United States)

    Li, Li-Li; Liu, Pei-Hong; Xie, Xiao-Hua; Ma, Su; Liu, Chao; Chen, Li; Qin, Chun-Lin

    2016-01-01

    FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam20A-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM20A. By breeding K14-Cre mice with Fam20Aflox/flox mice, we created K14-Cre;Fam20Aflox/flox (conditional knock out, cKO) mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography, histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam20A-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice. The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues. PMID:27281036

  4. Loss of epithelial FAM20A in mice causes amelogenesis imperfecta, tooth eruption delay and gingival overgrowth.

    Science.gov (United States)

    Li, Li-Li; Liu, Pei-Hong; Xie, Xiao-Hua; Ma, Su; Liu, Chao; Chen, Li; Qin, Chun-Lin

    2016-01-01

    FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam20A-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM20A. By breeding K14-Cre mice with Fam20A(flox/flox) mice, we created K14-Cre;Fam20A(flox/flox) (conditional knock out, cKO) mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography, histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam20A-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice. The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues.

  5. Effects of icariin on cytokine-induced ankylosing spondylitis with fibroblastic osteogenesis and its molecular mechanism.

    Science.gov (United States)

    Jia, Chunrong; Liu, Hongxiao; Li, Min; Wu, Zhikui; Feng, Xinghua

    2014-01-01

    The aim of this study is to explore the effects of icariin on cytokine induced ankylosing spondylitis fibroblast osteogenesis type expression and its molecular mechanism. The normal fibroblasts were collected as normal control group, and the fibroblasts of hip joint capsule of AS patients were collected, which were respectively added in fetal bovine serum (group AS), fetal bovine serum and cytokines (BMP-2+TGF-beta 1) (group AS), and cell factor solution (icariin group), and observed of the osteogenic expression of fibroblast, to evaluate the impact of Icariin on it. The ALP activity, the content of collagen, osteocalcin content and cbfa1mRNA and OCmRNA of fibroblast of AS group increased compared to the normal control group and AS control group (P < 0.01), indicating that icariin can significantly inhibit the above changes (P < 0.01). Icariin can inhibit fibroblast further osteogenic differentiation through inhibiting the effect of cytokines on the fibroblast osteogenesis type markers and osteogenic gene expression and osteogenic differentiation.

  6. Bimaxillary distraction osteogenesis used for treatment of crowding in non-growing individuals. Case report.

    Science.gov (United States)

    Corega, C; Vaida, L; Festila, D G; Rigoni, G; Albanese, M; D'Agostino, A; Chiarini, G; Nocini, P F; Bertossi, D

    2014-01-14

    Dental crowding is frequently associated with transverse jaw discrepancies, resulting in a less-than-ideal position of the teeth in the basal bone. The classic aproach for correcting bimaxillary crowding are extractions or arch expansion. Rapid maxilla-mandibular expansion was used to treat transverse discrepancies in growing patients, but with aging, the upper and lower jaw bones become increasingly resistant to expansion. The surgically assisted rapid maxillary expansion (SARME) and the mandibular midsymphyseal distraction osteogenesis procedure overcome this age limitation and are of great importance for the treatment of transverse discrepancies in adults. The aim of this paper is to report a case with a severe transverse deficiency treated with SARME, mandibular midsymphyseal distraction together with orthodontic treatment in an adult patient. The case highlights the esthetic advantages of increasing the transversal dimension of both jaws in patients with severe crowding associated with constricted dental arches and recommends the maxillo-mandibular transverse distraction osteogenesis as an and effective form of surgical treatment for patients with malocclusions or dentofacial deformities featuring severe transverse discrepancies, combined with a carefully monitored orthodontic treatment. PMID:24423741

  7. LNGFR induction during osteogenesis of human jaw periosteum-derived cells.

    Science.gov (United States)

    Alexander, Dorothea; Schäfer, Fabian; Munz, Adelheid; Friedrich, Björn; Klein, Christian; Hoffmann, Jürgen; Bühring, Hans-Jörg; Reinert, Siegmar

    2009-01-01

    Isolated jaw periosteum-derived cells (JPCs) comprise a morphologically heterogeneous population. There are no known specific surface markers that are able to distinguish between progenitors and cells of other tissue types. The aim of our study was to identify differentiation markers as predictors of JPC mineralization capacity. JPCs underwent osteogenic differentiation after cultivation in osteogenic medium containing known activators. By FACS analysis, we found the low affinity nerve growth factor receptor (LNGFR-CD271) to be induced during the first five days of osteogenesis and that it was expressed at higher levels in mineralizing JPCs (mJPCs) in comparison to non-mineralizing JPCs (nmJPCs). Similar results were obtained by semi-quantitative immunohistochemical stainings and western blot analyses. Quantitative real-time PCR results showed significantly higher LNGFR and alkaline phosphatase transcript levels in mJPCs compared to nmJPCs. LNGFR is a differentiation marker that distinguishes between mineralizing JPCs and non-mineralizing JPCs during the first phase of osteogenesis and can therefore be considered an early surface marker of osteogenic capacity in vitro. PMID:19710543

  8. A histological evaluation on osteogenesis and resorption of methotrexate-loaded calcium phosphate cement in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Li Dong; Yang Zhiping; Li Xin; Li Zhenfeng; Li Jianmin [Department of Orthopedics, Qilu Hospital of Shandong University, Shandong (China); Yang Jingyan, E-mail: yangzhiping@medmail.com.c [Department of Pathology, 2nd Affiliated Hospital of Shandong University, Shandong (China)

    2010-04-15

    In this study, we investigated the resorption of in vivo methotrexate-loaded calcium phosphate cement (MTX-CPC) implants and their effect on osteogenesis. MTX-CPC implants containing 1% methotrexate (MTX) (weight/weight) were preset and implanted into the femoral condyle of rabbits. Calcium phosphate cement (CPC) without MTX was used as the control. The femurs were harvested at day 1 and at 1, 3 and 6 months after implantation and radiological examination were performed. Decalcified sections were examined by hematoxylin and eosin (HE) staining, alkaline phosphatase (ALPase) immunohistochemistry and tartrate-resistant acid phosphatase (TRAPase) enzyme histochemistry. Then, we performed histomorphometric analysis, including determination of the percentage of newly formed bone and osteoblast and osteoclast counts. The results indicated that MTX-CPC implants were biocompatible, biodegradable and osteoconducive. However, MTX release from the implantation site inhibited osteogenesis in the initial period; this inhibition weakened with time, and no difference was observed between CPC and MTX-CPC at 6 months after implantation. Hence, MTX-CPC is an excellent material for filling defects and can be used for preparing effective drug delivery systems to achieve local control of invasive bone tumors.

  9. Modulation of Osteogenesis in MC3T3-E1 Cells by Different Frequency Electrical Stimulation.

    Directory of Open Access Journals (Sweden)

    Yu Wang

    Full Text Available Electrical stimulation (ES is therapeutic to many bone diseases, from promoting fracture regeneration to orthopedic intervention. The application of ES offers substantial therapeutic potential, while optimal ES parameters and the underlying mechanisms responsible for the positive clinical impact are poorly understood. In this study, we assembled an ES cell culture and monitoring device. Mc-3T3-E1 cells were subjected to different frequency to investigate the effect of osteogenesis. Cell proliferation, DNA synthesis, the mRNA levels of osteosis-related genes, the activity of alkaline phosphatase (ALP, and intracellular concentration of Ca2+ were thoroughly evaluated. We found that 100 Hz could up-regulate the mRNA levels of collagen I, collagen II and Runx2. On the contrary, ES could down-regulate the mRNA levels of osteopontin (OPN. ALP activity assay and Fast Blue RR salt stain showed that 100 Hz could accelerate cells differentiation. Compared to the control group, 100 Hz could promote cell proliferation. Furthermore, 1 Hz to 10 Hz could improve calcium deposition in the intracellular matrix. Overall, these results indicate that 100Hz ES exhibits superior potentialities in osteogenesis, which should be beneficial for the clinical applications of ES for the treatment of bone diseases.

  10. Influence of gravitational therapy on reparative osteogenesis in patients with osteomyelitis of lower extremities

    Directory of Open Access Journals (Sweden)

    Kotelnikov G.P.

    2010-09-01

    Full Text Available The article provides a comparative analysis of reparative osteogenesis in 105 patients with diffuse osteomyelitis of lower extremities, covering bone in diameter totally or subtotally. In complex treatment 51 patients have experienced gravitational therapy (study group, 54 patients have been treated by standard methods (control group. The study was conducted in clinics of Samara State Medical University. Gravitational therapy is a new noninvasive method of physiotherapy, first used in the treatment of patients with osteomyelitis. It is noted that the inclusion of gravitational therapy in complex treatment contributes to the consolidation of bone fragments, accelerates о ste о reparative processes in the regenerate bone formed in the zone of the defect in osteosynthesis in apparatus for external fixation. Past radionuclide study of the skeleton showed that the gravitational therapy positively affects the blood supply to the area osteomyelitic defeat, activates and improves bone metabolism. Osteodensimetric studies have shown that under the influence of gravitational therapy there was an increase in bone mineral density of the lower extremities, especially with the affected side, which was not observed in patients of control group. Gravitational therapy is an effective method of influence on reparative osteogenesis in patients with osteomyelitis of lower extremities

  11. A histological evaluation on osteogenesis and resorption of methotrexate-loaded calcium phosphate cement in vivo

    International Nuclear Information System (INIS)

    In this study, we investigated the resorption of in vivo methotrexate-loaded calcium phosphate cement (MTX-CPC) implants and their effect on osteogenesis. MTX-CPC implants containing 1% methotrexate (MTX) (weight/weight) were preset and implanted into the femoral condyle of rabbits. Calcium phosphate cement (CPC) without MTX was used as the control. The femurs were harvested at day 1 and at 1, 3 and 6 months after implantation and radiological examination were performed. Decalcified sections were examined by hematoxylin and eosin (HE) staining, alkaline phosphatase (ALPase) immunohistochemistry and tartrate-resistant acid phosphatase (TRAPase) enzyme histochemistry. Then, we performed histomorphometric analysis, including determination of the percentage of newly formed bone and osteoblast and osteoclast counts. The results indicated that MTX-CPC implants were biocompatible, biodegradable and osteoconducive. However, MTX release from the implantation site inhibited osteogenesis in the initial period; this inhibition weakened with time, and no difference was observed between CPC and MTX-CPC at 6 months after implantation. Hence, MTX-CPC is an excellent material for filling defects and can be used for preparing effective drug delivery systems to achieve local control of invasive bone tumors.

  12. The osteogenetic rate in alveolar bone remodeling induced by distraction osteogenesis of the periodontal ligament

    Institute of Scientific and Technical Information of China (English)

    WANG Shuang; FENG Pei-xun; GUO Xiong; ZHOU Hong

    2006-01-01

    Objective: To observe osteogenetic rate of alveolar bone on the tension side in orthodontic tooth movement through distraction osteogenesis of the periodental ligament quantificationally. Methods:The experiment was carried in 6 dogs. The left side of jaws of each one was set as test or control side, and the other side was control or test side. On the control side, the first premorlar was moved by traditional method on the test side. A self-made distraction device was used on the test side. The newly formed alveolar bone on the tension side of moved tooth was labeled by serial tetracycline fluorochrome. Sections were observed by fluorescence microscope and pictured. Newly formed bone was measured by computer image analysis. Results: The quantity of newly formed bone was significantly different between the two methods. Newly formed bone in rapid tooth movement by distraction osteogenesis of the periodental ligament was more than that in traditional method. Conclusion: The distraction through periodental ligament could induce more rapid bone formation and excite higher osteogenetic activity than traditional method.

  13. Study on vertical mandibular distraction osteogenesis using magnesium alloy on canine

    Institute of Scientific and Technical Information of China (English)

    Chengyue Wang; Shufeng Wang; Yusheng Yao; Fuzhai Cui

    2014-01-01

    The bone formation feasibility by a novel magnesium alloy device was evaluated using a canine vertical mandibular distraction osteogenesis (DO) model. Osteotomies were performed in the area where last 3 star's teeth of left mandibular were pulled out before 3 months. Both AZ31 magnesium alloy (n=6) and 316L stainless steel (n=6) distraction devices were implanted. The distraction osteogenesis was carried out with a latency of 5 days after mandibular osteotomy. Distraction proceeded at a rate of 0.3 mm/8 h for 7 days and followed by 4 weeks of consolidations. The evaluations were conducted by scanning electron microscopy (SEM) and histological examinations. There were osteoblasts and trabecular bones formations manifestly in both groups. There was no significant difference in the bone mineral density between the two groups. The surface of the magnesium alloy was much more cracked and uneven, resulting from the surface pitting corrosion. The crew nails were closely combined with the surrounding bone tissue. AZ31 magnesium alloy exhibited a certain degradation rate in mandibular and did not post a negative effect on the kidney and liver. The observations in magnesium alloys group is consistent with the stainless steel group.

  14. Complications of mandibular distraction osteogenesis for developmental deformities: a systematic review of the literature.

    Science.gov (United States)

    Verlinden, C R A; van de Vijfeijken, S E C M; Tuinzing, D B; Jansma, E P; Becking, A G; Swennen, G R J

    2015-01-01

    A systematic review of English and non-English articles on the complications of mandibular distraction osteogenesis (MDO) for patients with developmental deformities was performed, in accordance with the PRISMA statement. Search terms expressing distraction osteogenesis were used in 'AND' combination with search terms comprising 'mandible' and terms for complication, failure, and morbidity. A search using PubMed (National Library of Medicine, NCBI), EMBASE, and Cochrane Controlled Trials Register yielded 644 articles published between 1966 and mid October 2013. Clinical articles that reported complications related to MDO in developmental deformities were included. Two hundred and fifty articles were eligible and were screened in detail. A total of 32 articles reporting the cases of 565 patients were finally included. Patients underwent mandibular lengthening and transverse widening. A total of 211 complications were reported (37.4%); these were classified according to an index that indicates the clinical impact. Inferior alveolar nerve (IAN) neurosensory disturbances, minor infection, device failure, anterior open bite, permanent dental damage, and skeletal relapse were most represented. Complications that resolved spontaneously (type I) were seen in 11.0%, medically or technically manageable complications, without hospitalization, were seen in 10.8% (type II), and permanent complications (type VI) were seen in 9.6%.

  15. Study on vertical mandibular distraction osteogenesis using magnesium alloy on canine

    Directory of Open Access Journals (Sweden)

    Chengyue Wang

    2014-10-01

    Full Text Available The bone formation feasibility by a novel magnesium alloy device was evaluated using a canine vertical mandibular distraction osteogenesis (DO model. Osteotomies were performed in the area where last 3 star׳s teeth of left mandibular were pulled out before 3 months. Both AZ31 magnesium alloy (n=6 and 316L stainless steel (n=6 distraction devices were implanted. The distraction osteogenesis was carried out with a latency of 5 days after mandibular osteotomy. Distraction proceeded at a rate of 0.3 mm/8 h for 7 days and followed by 4 weeks of consolidations. The evaluations were conducted by scanning electron microscopy (SEM and histological examinations. There were osteoblasts and trabecular bones formations manifestly in both groups. There was no significant difference in the bone mineral density between the two groups. The surface of the magnesium alloy was much more cracked and uneven, resulting from the surface pitting corrosion. The crew nails were closely combined with the surrounding bone tissue. AZ31 magnesium alloy exhibited a certain degradation rate in mandibular and did not post a negative effect on the kidney and liver. The observations in magnesium alloys group is consistent with the stainless steel group.

  16. Distraction osteogenesis and orthognathic surgery for a patient with unilateral cleft lip and palate.

    Science.gov (United States)

    Kim, Ji Hyun; Lee, Il Hong; Lee, Sang Min; Yang, Byoung Eun; Park, In Young

    2015-03-01

    Maxillary deficiency is a common feature in patients with repaired cleft lip and palate. Orthognathic surgery has been the conventional approach for the management of cleft-related maxillary hypoplasia. However, for patients with a severe maxillary deficiency, orthognathic surgery alone has many disadvantages, such as high relapse rates of 25% to 40%, instability, limited amount of advancement, and a highly invasive surgical technique. As an alternative treatment method, distraction osteogenesis has been used successfully in the distraction of the mandible, the maxilla, the entire midface, and the orbits as well as the cranial bones, with stable outcomes. The type of distraction device, either external or internal, can be chosen based on the surgical goals set for the patient. In this study, we report on the use of a rigid external distraction device for maxillary advancement in a 22-year-old woman with a repaired unilateral cleft lip and palate and severe maxillary hypoplasia. After the distraction osteogenesis, 2-jaw surgery was performed to correct the maxillary yaw deviation and the mandibular prognathism.

  17. Temporo-spatial analysis of Osterix, HNK1 and Sox10 during odontogenesis and maxillaries osteogenesis.

    Science.gov (United States)

    Tomazelli, Karin Berria; Modolo, Filipe; Trentin, Andrea Gonçalves; Garcez, Ricardo Castilho; Biz, Michelle Tillmann

    2015-10-01

    Cell differentiation is essential for maxillaries and tooth development. Facial mesenchymal tissue is formed by neural crest cells (NC). These cells are highly migratory, giving rise to various cell types, considered with a high level of plasticity, indicating that they contain progenitor cells with a great power of differentiation. In this study, it was analyzed the presence of NC cell progenitors and mesenchymal stem cells (MSC) during maxillaries osteogenesis and odontogenesis in rats. Histological slides were collected in two phases: embryonic age of 15 and 17 days; 2, 4 and 7 days after birth. Immunohistochemistry for MSC markers (Osterix) and NC cells (Sox10, HNK1) was performed. The results showed positive expression for Osterix and HNK1 in undifferentiated ectomesenchymal cells in early and late stages; Sox10 was present only in early stages in undifferentiated cells. All markers were present in differentiated cells. Although the experiments performed do not allow us to explain a possible role for Osx, HNK1 and Sox10 in both differentiated and undifferentiated cells during osteogenesis and odontogenesis, it had shown important results not yet described: the presence of HNK1 and Sox10 in osteoblasts and odontoblasts in late development stages and in the tooth germ epithelial cells and ameloblasts. PMID:26253417

  18. The genetics of amelogenesis imperfecta: a review of the literature Genética da amelogênese imperfeita: uma revisão da literatura

    OpenAIRE

    Maria Cristina Leme Godoy dos Santos; Sergio Roberto Peres Line

    2005-01-01

    A melogenesis imperfecta (AI) is a group of inherited defects of dental enamel formation that show both clinical and genetic heterogeneity. Enamel findings in AI are highly variable, ranging from deficient enamel formation to defects in the mineral and protein content. Enamel formation requires the expression of multiple genes that transcribes matrix proteins and proteinases needed to control the complex process of crystal growth and mineralization. The AI phenotypes depend on the specific ge...

  19. Reactivation of trigeminal neuralgia following distraction osteogenesis in an 8-year-old child: Report of a unique case

    Directory of Open Access Journals (Sweden)

    Ramanathan M

    2007-03-01

    Full Text Available Trigeminal neuralgia is extremely rare in children. No concrete treatment protocols seem to be available for management of this condition in the pediatric population. Although trigeminal neuralgia may achieve remission, the possibility of reactivation of a hitherto quiescent condition cannot be ruled out. We present a case of pediatric trigeminal neuralgia following distraction osteogenesis of the mandible.

  20. Long-lasting neurosensory disturbance following advancement of the retrognathic mandible : distraction osteogenesis versus bilateral sagittal split osteotomy

    NARCIS (Netherlands)

    Wijbenga, J. G.; Verlinden, C. R. A.; Jansma, J.; Becking, A. G.; Stegenga, B.

    2009-01-01

    Neurosensory disturbance (NSD) of the inferior alveolar nerve (IAN) is the most common complication after bilateral sagittal split osteotomy (BSSO) and distraction osteogenesis (DO) of the retrognathic mandible. It is suggested that the risk is lower after DO than after BSSO. This retrospective stud

  1. Three-dimensional computed tomographic evaluation of Le Fort III distraction osteogenesis with an external device in syndromic craniosynostosis.

    Science.gov (United States)

    Wery, M F; Nada, R M; van der Meulen, J J; Wolvius, E B; Ongkosuwito, E M

    2015-03-01

    There is little anteroposterior growth of the midface in patients with syndromic craniosynostosis who are followed up over time without intervention. A Le Fort III with distraction osteogenesis can be done to correct this. This is a controlled way in which to achieve appreciable stable advancement of the midface without the need for bone grafting, but the vector of the movement is not always predictable. The purpose of this study was to evaluate the 3-dimensional effect of Le Fort III distraction osteogenesis with an external frame. Ten patients (aged 7-19 years) who had the procedure were included in the study. The le Fort III procedure and the placement of the external frame were followed by an activation period and then a 3-month retention period. Computed tomographic (CT) images taken before and after operation were converted and loaded into 3-dimensional image rendering software and compared with the aid of a paired sample t test and a colour-coded qualitative analysis. Comparison of the CT data before and after distraction indicated that the amount of midface advancement was significant. Le Fort III distraction osteogenesis is an effective way to advance the midface. However, the movement during osteogenesis is not always exactly in the intended direction, and a secondary operation is often necessary. Three-dimensional evaluation over a longer period of time is necessary.

  2. Evaluation of inferior alveolar nerve regeneration by bifocal distraction osteogenesis with retrograde transportation of horseradish peroxidase in dogs.

    Directory of Open Access Journals (Sweden)

    Yosuke Shogen

    Full Text Available BACKGROUND: Bifocal distraction osteogenesis has been shown to be a reliable method for reconstructing segmental mandibular defects. However, there are few reports regarding the occurrence of inferior alveolar nerve regeneration during the process of distraction. Previously, we reported inferior alveolar nerve regeneration after distraction, and evaluated the regenerated nerve using histological and electrophysiological methods. In the present study, we investigated axons regenerated by bifocal distraction osteogenesis using retrograde transportation of horseradish peroxidase in the mandibles of dogs to determine their type and function. METHODS AND FINDINGS: Using a bifocal distraction osteogenesis method, we produced a 10-mm mandibular defect, including a nerve defect, in 11 dogs and distracted using a transport disk at a rate of 1 mm/day. The regenerated inferior alveolar nerve was evaluated by retrograde transportation of HRP in all dogs at 3 and 6 months after the first operation. At 3 and 6 months, HRP-labeled neurons were observed in the trigeminal ganglion. The number of HRP-labeled neurons in each section increased, while the cell body diameter of HRP-labeled neurons was reduced over time. CONCLUSIONS: We found that the inferior alveolar nerve after bifocal distraction osteogenesis successfully recovered until peripheral tissue began to function. Although our research is still at the stage of animal experiments, it is considered that it will be possible to apply this method in the future to humans who have the mandibular defects.

  3. Long-term functional and quality of live assessment following post-traumatic distraction osteogenesis of the lower limb

    NARCIS (Netherlands)

    N.W.L. Schep (Niels); E.M.M. van Lieshout (Esther); P. Patka (Peter); L.M.M. Vogels (Lucas)

    2009-01-01

    textabstractLimb length discrepancy and segmental bone defects can be difficult problems to manage after fractures of the lower limb. Distraction osteogenesis can be applied to lengthen bone or to bridge intercalary defects by segmental bone transport. The purpose of this study was to assess the fun

  4. Mechanically-induced osteogenesis in the cortical bone of pre- to peripubertal stage and peri- to postpubertal stage mice

    Directory of Open Access Journals (Sweden)

    Plochocki Jeffrey H

    2009-06-01

    Full Text Available Abstract Background Exercise during postnatal development plays a key role in determining adult bone mass and reducing the risk of fracture and osteoporosis later in life. However, the relationship between mechanically-induced osteogenesis and age is unclear. Elevated levels of estrogen during puberty may inhibit periosteal bone formation. Thus, magnitudes of mechanically-induced osteogenesis may be vary with pubertal state. Methods The present study uses a murine model to examine age-related changes in bone formation at the femoral midshaft with voluntary exercise. Pre- to peripubertal mice aged 3 weeks and peri- to postpubertal mice aged 7 weeks were randomly divided into sedentary and exercised groups and subjected to histomorphometric comparison after 4 weeks of treatment. Results Results of the experiment indicate that exercise significantly increased osteogenesis on the periosteal and endocortical surface of the mice in the older age group (P P Conclusion These findings suggest that the amount and location of mechanically-induced osteogenesis differs by age during skeletal development. Late adolescence may be the optimal time to accrue bone mass and maximize bone strength.

  5. Upregulation of BMSCs Osteogenesis by Positively-Charged Tertiary Amines on Polymeric Implants via Charge/iNOS Signaling Pathway

    Science.gov (United States)

    Zhang, Wei; Liu, Na; Shi, Haigang; Liu, Jun; Shi, Lianxin; Zhang, Bo; Wang, Huaiyu; Ji, Junhui; Chu, Paul K.

    2015-03-01

    Positively-charged surfaces on implants have a similar potential to upregulate osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) as electromagnetic therapy approved for bone regeneration. Generally, their osteogenesis functions are generally considered to stem from the charge-induced adhesion of extracellular matrix (ECM) proteins without exploring the underlying surface charge/cell signaling molecule pathways. Herein, a positively-charged surface with controllable tertiary amines is produced on a polymer implant by plasma surface modification. In addition to inhibiting the TNF-α expression, the positively-charged surface with tertiary amines exhibits excellent cytocompatibility as well as remarkably upregulated osteogenesis-related gene/protein expressions and calcification of the contacted BMSCs. Stimulated by the charged surface, these BMSCs display high iNOS expressions among the three NOS isoforms. Meanwhile, downregulation of the iNOS by L-Can or siRNA inhibit osteogenic differentiation in the BMSCs. These findings suggest that a positively-charged surface with tertiary amines induces osteogenesis of BMSCs via the surface charge/iNOS signaling pathway in addition to elevated ECM protein adhesion. Therefore, creating a positively-charged surface with tertiary amines is a promising approach to promote osseointegration with bone tissues.

  6. Combined exposure to big endothelin-1 and mechanical loading in bovine sternal cores promotes osteogenesis.

    Science.gov (United States)

    Meyer, Luisa A; Johnson, Michael G; Cullen, Diane M; Vivanco, Juan F; Blank, Robert D; Ploeg, Heidi-Lynn; Smith, Everett L

    2016-04-01

    Increased bone formation resulting from mechanical loading is well documented; however, the interactions of the mechanotransduction pathways are less well understood. Endothelin-1, a ubiquitous autocrine/paracrine signaling molecule promotes osteogenesis in metastatic disease. In the present study, it was hypothesized that exposure to big endothelin-1 (big ET1) and/or mechanical loading would promote osteogenesis in ex vivo trabecular bone cores. In a 2×2 factorial trial of daily mechanical loading (-2000με, 120cycles daily, "jump" waveform) and big ET1 (25ng/mL), 48 bovine sternal trabecular bone cores were maintained in bioreactor chambers for 23days. The bone cores' response to the treatment stimuli was assessed with percent change in core apparent elastic modulus (ΔEapp), static and dynamic histomorphometry, and prostaglandin E2 (PGE2) secretion. Two-way ANOVA with a post hoc Fisher's LSD test found no significant treatment effects on ΔEapp (p=0.25 and 0.51 for load and big ET1, respectively). The ΔEapp in the "no load + big ET1" (CE, 13±12.2%, p=0.56), "load + no big ET1" (LC, 17±3.9%, p=0.14) and "load + big ET1" (LE, 19±4.2%, p=0.13) treatment groups were not statistically different than the control group (CC, 3.3%±8.6%). Mineralizing surface (MS/BS), mineral apposition (MAR) and bone formation rates (BFR/BS) were significantly greater in LE than CC (p=0.037, 0.0040 and 0.019, respectively). While the histological bone formation markers in LC trended to be greater than CC (p=0.055, 0.11 and 0.074, respectively) there was no difference between CE and CC (p=0.61, 0.50 and 0.72, respectively). Cores in LE and LC had more than 50% greater MS/BS (p=0.037, p=0.055 respectively) and MAR (p=0.0040, p=0.11 respectively) than CC. The BFR/BS was more than two times greater in LE (p=0.019) and LC (p=0.074) than CC. The PGE2 levels were elevated at 8days post-osteotomy in all groups and the treatment groups remained elevated compared to the CC group on days 15

  7. Nanostructured gel scaffolds for osteogenesis through biological assembly of biopolymers via specific nucleobase pairing.

    Science.gov (United States)

    Fan, Ming; Yan, Jingxuan; Tan, Huaping; Ben, Dandan; He, Qiuling; Huang, Zhongwei; Hu, Xiaohong

    2014-11-01

    Biopolymer-based gel scaffolds have great potential in the field of tissue regenerative medicine. In this work, a nanostructured biopolymer gel scaffold via specific pairing of functionalized nucleobases was developed for specifically targeted drug delivery and in vitro osteogenesis. The biopolymer gel system was established by the Watson-Crick base pairing between thymine and adenine via the hydrogen bonding. As gel scaffold precursors, opposite charged polysaccharide derivatives, e.g. quaternized cellulose and heparin, could be additionally crosslinked by extra electrostatic interactions. The potential application of this gel scaffold in bone tissue engineering was confirmed by encapsulation behavior of osteoblasts. In combination with cell growth factor, e.g. bone morphogenetic protein, the nanostructured gel scaffold exhibited beneficial effects on osteoblast activity and differentiation, which suggested a promising future for local treatment of pathologies involving bone loss.

  8. Mandibular distraction osteogenesis in the micrognathic neonate: a review for neonatologists and pediatricians.

    Science.gov (United States)

    Hong, Paul; Bezuhly, Michael

    2013-06-01

    In the past, severe neonatal upper airway obstruction secondary to micrognathia was managed with a tracheostomy. Although effective, tracheostomy can cause many short-term and long-term complications. More recently, mandibular distraction osteogenesis (MDO) has become a well-accepted surgical option in treating micrognathic newborns. Overall, MDO has been reported to be an effective intervention in alleviating the micrognathia-associated airway compromise. Furthermore, it seems to be well tolerated and has supplanted the need for tracheostomy in many patients. Neonatologists and pediatricians commonly care for these children, and therefore an up-to-date clinical narrative review regarding MDO is presented to increase the awareness of this relatively new surgical option.

  9. 牙颌面畸形的牵引成骨%Distraction osteogenesis in dentomatillofacial detormity

    Institute of Scientific and Technical Information of China (English)

    颜传杰; 沈军; 张晏更

    2004-01-01

    牵引成骨(Distraction Osteogenesis)是通过牵张器固定在切开后仍保留骨膜及软组织附着与血供的骨段施行缓慢牵引以延长或重建骨组织及软组织的一项技术。相对于传统正颌手术,无需植骨,减少供区创伤,骨周围的软组织可同期获得扩张,且治疗范围广泛,从新生儿到成人均有成功范例。因此,自90年代以来,该技术已广泛用于治疗各种严重的牙颌面畸形。

  10. Magnetic resonance microscopy for monitoring osteogenesis in tissue-engineered construct in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xu Huihui [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Othman, Shadi F [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Hong Liu [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Peptan, Ioana A [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Magin, Richard L [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States)

    2006-02-07

    Magnetic resonance microscopy (MRM) is used to monitor osteogenesis in tissue-engineered constructs. Measurements of the developing tissue's MR relaxation times (T{sub 1} and T{sub 2}), apparent diffusion coefficient (ADC) and elastic shear modulus were conducted over a 4-week growth period using an 11.74 T Bruker spectrometer with an imaging probe adapted for MR elastography (MRE). Both the relaxation times and the ADC show a statistically significant decrease after only one week of tissue development while the tissue stiffness increases progressively during the first two weeks of in vitro growth. The measured MR parameters are correlated with histologically monitored osteogenic tissue development. This study shows that MRM can provide quantitative data with which to characterize the growth and development of tissue-engineered bone.

  11. Scaffold pore size modulates in vitro osteogenesis of human adipose-derived stem/stromal cells

    International Nuclear Information System (INIS)

    Trabecular bone has an interconnected porous structure, which influences cellular responses, biochemical transport and mechanical strength. Appropriately mimicking this structural organization in biomaterial scaffolds can facilitate more robust bone tissue regeneration and integration by providing a native microenvironment to the cells. This study examined the effect of pore size on human adipose-derived stem/stromal cell (ASC) osteogenesis within poly(ε-caprolactone) (PCL) scaffolds. Scaffold pore size was controlled by porogen leaching of custom-made paraffin particles with three different size ranges: P200 (< 500 µm), P500 (500–1000 µm), and P1000 (1000–1500 µm). Scaffolds produced by leaching these particles exhibited highly interconnected pores and rough surface structures that were favorable for cell attachment and ingrowth. The osteogenic response of ASCs was evaluated following 3 weeks of in vitro culture using biochemical (ALP, Ca2+/DNA content), mechanical (compression test) and histological (H and E and von Kossa staining) analyses. It was observed that while the total number of cells was similar for all scaffolds, the cell distributions and osteogenic properties were affected by the scaffold pore size. ASCs were able to bridge smaller pores and grow uniformly within these scaffolds (P200) while they grew as a layer along the periphery of the largest pores (P1000). The cell-biomaterial interactions specific to the latter case led to enhanced osteogenic responses. The ALP activity and Ca2+ deposition were doubled in P1000 scaffolds as compared to P200 scaffolds. A significant difference was observed between the compressive strength of unseeded and seeded P1000 scaffolds. Therefore, we demonstrated that the use of scaffolds with pores that are in the range of 1 mm enhances in vitro ASC osteogenesis, which may improve their performance in engineered bone substitutes. (paper)

  12. Rapid tooth movement through distraction osteogenesis of the periodontal ligament in dogs

    Institute of Scientific and Technical Information of China (English)

    AI Hong; XU Qing-feng; LU Hong-fei; MAI Zhi-hui; AN Ai-qun; LIU Guo-ping

    2008-01-01

    Background Animal models are needed for the study of rapid tooth movement into the extraction socket through distraction osteogenesis of the periodontal ligament.Methods Modified distraction devices were placed on eight dogs between the first and third mandibular premolars on the left sides;similar placement of traditional straight wise appliances on the right sides served as the control.The experimental distractors were activated(0.25 mm/d)twice a day and the control devices were activated(100 g)for two weeks with consolidation periods at weeks two,three,six,and ten.Two dogs were sacrificed at each consolidation time point;rates and patterns of tooth movement,loss of anchorage,and periapical films were evaluated,and the aftected premolars and surrounding periodontal tissues were decalcified and examined histologically.General observations,X-ray periapical filming and histology examination were performed.Results Distal movement((3.66±0.1 4)mm)measured two weeks after modified distraction exceeded that achieved using the traditional device((1.15±0.21)mm;P<0.05).Loss of anchorage was minimally averaged(0.34±0.06)mm and (0.32±0.07)mm in the experimental and control sides,respectively.By radiography,apical and lateral surface root resorptions on both sides were minimal.Alveolar bone Iesions were never evident.Fibroblasts were endched in periodontal ligaments and bone spicules formed actively along directions of distraction.Conclusions The canine model is suitable for the study of rapid tooth movement through distraction osteogenesis of the periodontal ligament.The technique accelerates tooth movement,periodontal remodeling,alveolar bone absorption,and may induce fibroblast formation,as compared to the traditional orthodontic method,without adversely affecting root absorption,bone loss,tooth mobility and anchorage loss.

  13. Collagens VI and XII form complexes mediating osteoblast interactions during osteogenesis.

    Science.gov (United States)

    Izu, Yayoi; Ezura, Yoichi; Koch, Manuel; Birk, David E; Noda, Masaki

    2016-06-01

    Bone formation is precisely regulated by cell-cell communication in osteoblasts. We have previously demonstrated that genetic deletion of Col6a1 or Col12a1 impairs osteoblast connections and/or communication in mice, resulting in bone mass reduction and bone fragility. Mutations of the genes encoding collagen VI cause Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM), which have overlapping phenotypes involving connective tissue and muscle. Recent studies have identified COL12A1 gene mutations in patients with UCMD- and BM-like disorders harboring no COL6 mutations, indicating the shared functions of these collagens in connective tissue homeostasis. The purpose of this investigation has been to test the hypothesis that collagens VI and XII have coordinate regulatory role(s) during bone formation. We analyzed the localization of collagens VI and XII relative to primary osteoblasts during osteogenesis. Immunofluorescence analysis demonstrated that collagens VI and XII colocalized in matrix bridges between adjacent cells during periods when osteoblasts were establishing cell-cell connections. Quantification of cells harboring collagen bridges demonstrated that matrix bridges were composed of collagens VI and XII but not collagen I. Interestingly, matrix bridge formation was impaired in osteoblasts deficient in either Col6a1 or Col12a1, suggesting that both collagens were indispensable for matrix bridge formation. These data demonstrate, for the first time, a functional relationship between collagens VI and XII during osteogenesis and indicate that a complex containing collagens VI and XII is essential for the formation of a communicating cellular network during bone formation. PMID:26753503

  14. Surgical Management of Pierre Robin Sequence: Using Mandibular Distraction Osteogenesis to Address Hypoventilation and Failure to Thrive in Infancy.

    Science.gov (United States)

    Scott, Andrew R

    2016-04-01

    Mandibular hypoplasia may present in isolation or in the context of glossoptosis and a U-shaped, incomplete cleft palate. This latter triad is referred to as Pierre Robin sequence. Deleterious effects of micrognathia that may present during infancy are due primarily to glossoptosis or posterior displacement of the tongue. This tongue base prolapse may cause varying degrees of upper airway obstruction. A surgical option for management of tongue base airway obstruction secondary to mandibular hypoplasia is neonatal mandibular distraction osteogenesis. Herein, the author seeks to outline the benefits and limitations of early mandibular distraction osteogenesis as a way of managing airway obstruction and feeding difficulty in newborns with micrognathia. A description of the author's operative technique as well as potential complications and pitfalls will also be discussed. PMID:27097139

  15. REPARATIVE OSTEOGENESIS DURING TREATMENT OF FRACTURE UNDER TRANSOSSEOUS OSTEOSYNTHESIS AND INTRAMEDULLARY INSERTION OF WIRES WITH HYDROXYAPATITE COATING

    Directory of Open Access Journals (Sweden)

    Iurii M. Irianov, Arnold V. Popkov, Nikolay A. Kiryanov, Tatiana Iu. Karaseva, Evgenii A. Karasev

    2015-04-01

    Full Text Available Background: The problem of improving medical care for patients with the locomotor system injuries is very important especially last time. Material and Methods: Canine open comminuted tibial fractures modelled experimentally, wires with hydroxyapatite coating inserted intramedullary, osteosynthesis performed with the Ilizarov fixator. Regenerated bones investigated 14-360 days after surgery using the techniques of light microscopy, scanning and transmission electron microscopy, and X-ray electron probe microanalysis for histologic sections . Results: It has been found that a zone of active reparative osteo- and angiogenesis forms around the wires, as well as a bone sheath with the properties of osteogenesis conductor and inductor. Fracture consolidation occurs early according to the primary type without cartilaginous and connective tissue formation in bone adhesion. Presented morphological characteristics endovasal angiogenesis. Conclusion: The results of the study evidence of the positive effect of intramedullary wires with hydroxyapatite coating on the course and intensity of reparative osteogenesis during fracture healing

  16. Management of obstructive sleep apnea syndrome secondary to temporomandibular joint ankylosis by mandibular elongation using distraction osteogenesis

    Directory of Open Access Journals (Sweden)

    Yadavalli Guruprasad

    2012-01-01

    Full Text Available Obstructive sleep apnea syndrome (OSAS is associated with repetitive nocturnal upper airway obstruction leading to daytime sleepiness, cardiovascular derangements, and can be a debilitating, even life-threatening condition. The most favorable treatment for patients with OSAS is multidisciplinary care by a team that represents various dental and medical disciplines. Prescribed therapies might include weight loss, behavior modification, oral appliances, soft tissue surgery, skeletal surgery, or some combination of approaches. Osteogenesis by mandibular distraction has proved effective in children in the treatment of obstructive apnea syndrome associated with congenital malformations. In the adult, the possibility of using distraction osteogenesis in the management of OSAS remains to be defined. We report a case of an adult patient treated for OSAS secondary to temporomandibular joint ankylosis by mandibular distraction followed by interpositional arthroplasty.

  17. Surgical Management of Pierre Robin Sequence: Using Mandibular Distraction Osteogenesis to Address Hypoventilation and Failure to Thrive in Infancy.

    Science.gov (United States)

    Scott, Andrew R

    2016-04-01

    Mandibular hypoplasia may present in isolation or in the context of glossoptosis and a U-shaped, incomplete cleft palate. This latter triad is referred to as Pierre Robin sequence. Deleterious effects of micrognathia that may present during infancy are due primarily to glossoptosis or posterior displacement of the tongue. This tongue base prolapse may cause varying degrees of upper airway obstruction. A surgical option for management of tongue base airway obstruction secondary to mandibular hypoplasia is neonatal mandibular distraction osteogenesis. Herein, the author seeks to outline the benefits and limitations of early mandibular distraction osteogenesis as a way of managing airway obstruction and feeding difficulty in newborns with micrognathia. A description of the author's operative technique as well as potential complications and pitfalls will also be discussed.

  18. Hypoxia and Amino Acid Supplementation Synergistically Promote the Osteogenesis of Human Mesenchymal Stem Cells on Silk Protein Scaffolds

    OpenAIRE

    Sengupta, Sejuti; Park, Sang-Hyug; Patel, Atur; Carn, Julia; Lee, Kyongbum; Kaplan, David L.

    2010-01-01

    Tailoring tissue engineering strategies to match patient- and tissue-specific bone regeneration needs offers to improve clinical outcomes. As a step toward this goal, osteogenic outcomes and metabolic parameters were assessed when varying inputs into the bone formation process. Silk protein scaffolds seeded with human mesenchymal stem cells in osteogenic differentiation media were used to study in vitro osteogenesis under varied conditions of amino acid (lysine and proline) concentration and ...

  19. Ectopic Osteogenesis of Macroscopic Tissue Constructs Assembled from Human Mesenchymal Stem Cell-Laden Microcarriers through In Vitro Perfusion Culture

    OpenAIRE

    Maiqin Chen; Min Zhou; Zhaoyang Ye; Yan Zhou; Wen-Song Tan

    2014-01-01

    We had previously demonstrated the feasibility of preparing a centimeter-sized bone tissue construct by following a modular approach. In the present study, the objectives were to evaluate osteogenesis and tissue formation of human amniotic mesenchymal stem cells-laden CultiSpher S microcarriers during in vitro perfusion culture and after subcutaneous implantation. Microtissues were prepared in dynamic culture using spinner flasks in 28 days. In comparison with 1-week perfusion culture, microt...

  20. Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet-Rich Plasma Accelerate Distraction Osteogenesis in A Canine Model

    OpenAIRE

    2015-01-01

    Objective: Distraction osteogenesis (DO) is a surgical procedure used to generate large volumes of new bone for limb lengthening. Materials and Methods: In this animal experimental study, a 30% lengthening of the left tibia (mean distraction distance: 60.8 mm) was performed in ten adult male dogs by callus distraction after osteotomy and application of an Ilizarov fixator. Distraction was started on postoperative day seven with a distraction rate of 0.5 mm twice per day and car...

  1. SPATIAL AND TEMPORAL DISTRIBUTION OF GROWTH FACTORS RECEPTORS IN THE CALLUS: IMPLICATIONS FOR IMPROVEMENT OF DISTRACTION OSTEOGENESIS

    OpenAIRE

    SIWICKA, KAROLINA A; Kitoh, Hiroshi; KAWASUMI, MOTOAKI; Ishiguro, Naoki

    2011-01-01

    ABSTRACT Management of bone deficits by distraction osteogenesis is an appreciated but lengthy procedure. To accelerate the consolidation of newly formed distraction callus, an administration of growth factors into the distraction gap has been suggested. Changes in expression of growth factors receptors in the distracted callus during consolidation were studied in order to improve our understanding of the underlying molecular mechanisms and to provide a scientific basis for clinical applicati...

  2. Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation

    OpenAIRE

    Kim, Ji-Beom; Lee, Dong Yeon; Seo, Sang Gyo; Kim, Eo Jin; Kim, Ji Hye; Yoo, Won Joon; Cho, Tae-Joon; Choi, In Ho

    2015-01-01

    Background Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction. Methods The immature rabbit tibial DO model (20 mm length-gain) was u...

  3. Osteogenesis of bone marrow mesenchymal stem cells on strontium-substituted nano-hydroxyapatite coated roughened titanium surfaces

    OpenAIRE

    Yang, Hua-Wei; Lin, Mao-Han; Xu, Yuan-Zhi; Shang, Guang-Wei; Wang, Rao-Rao; Chen, Kai

    2015-01-01

    Objective: To investigate osteogenesis of bone marrow mesenchymal stem cells (BMSCs) on strontium-substituted nano-hydroxyapatite (Sr-HA) coated roughened titanium surfaces. Methods: Sr-HA coating and HA coating were fabricated on roughened titanium surfaces by electrochemical deposition technique and characterized by field emission scanning electron microscope (FESM). BMSCs were cultured on Sr-HA coating, HA coating and roughened titanium surfaces respectively. Cell proliferation, alkaline p...

  4. Histological changes following surgically-assisted rapid tooth movement through resistance reduction and distraction osteogenesis in dogs

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To investigate the histological changes of rapid tooth movement in dogs treated by resistance reduction and distraction osteogenesis,aiming to establish an animal model and further to reveal the remodeling mechanism of rapid tooth movement. Methods A total of 8 local hybrid dogs were selected as subjects for this study. The second pre-molar was extracted on both sides. The experimental side underwent alvelor surgery for resistance reduction and a home-made tooth-borne intraoral distraction device ...

  5. Influence of osteocytes in the in vitro and in vivo β-tricalcium phosphate-stimulated osteogenesis.

    Science.gov (United States)

    Chen, Zetao; Wu, Chengtie; Yuen, Jones; Klein, Travis; Crawford, Ross; Xiao, Yin

    2014-08-01

    Osteocytes, known to act as the main regulators of bone homeostasis, have become a major focus in the field of bone research. Bioactive ceramics have been widely used for bone regeneration. However, there are few studies about the interaction of osteocytes with bioceramics. The effects of osteocytes on the in vitro and in vivo osteogenesis of bioceramics are also unclear. The aim of this study was to investigate the role of osteocytes on the β-tricalcium phosphate (β-TCP) stimulated osteogenesis. It was found that osteocytes responded to the β-TCP stimulation, leading to the release of Wnt (wingless-related MMTV integration site), which enhanced osteogenic differentiation of bone marrow stromal cells via Wnt signaling pathway. Receptor activator of nuclear factor kappa B ligand, an osteoclast inducer, was also upregulated, indicating that osteocytes would also participated in activation of osteoclasts, which played a major role in the degradation process of β-TCP and new bone remodeling. In vivo studies further demonstrated that when the material was completely embedded by newly formed bone, the only cell contacting with the material was osteocyte. However, the material would eventually be degraded and replaced by the new bone, requiring the participation of osteoclasts and osteoblasts, which were demonstrated by using immunostaining in this study. As the only cell contacting with the material, osteocytes probably acted in a regulatory role to regulate the surrounding osteoclasts and osteoblasts. Osteocytes were also found to participate in the maturation of osteoblasts and the mineralization process of biomaterials, by upregulating E11 (podoplanin) and dentin matrix protein 1 expression. These findings indicated that osteocytes involved in bone biomaterial-mediated osteogenesis and biomaterial degradation, providing valuable insights into the mechanism of material-stimulated osteogenesis, and a novel strategy to optimize the evaluating system for the

  6. Noninvasive and multidisciplinary approach to the functional and esthetic rehabilitation of amelogenesis imperfecta: a pediatric case report.

    Science.gov (United States)

    de Souza, Juliana Feltrin; Fragelli, Camila Maria Bullio; Paschoal, Marco Aurélio Benini; Campos, Edson Alves; Cunha, Leonardo Fernandes; Losso, Estela Maris; Cordeiro, Rita de Cássia Loiola

    2014-01-01

    Case Report. An 8-year-old girl with amelogenesis imperfecta (AI) reported unsatisfactory aesthetics, difficulty in mastication, and dental hypersensitivity. The intraoral examination observed mixed dentition, malocclusion in anteroposterior relationships, anterior open bite, and dental asymmetry. A hypoplastic form of AI was diagnosed in the permanent dentition. A multidisciplinary planning was performed and divided into preventive, orthopedic, and rehabilitation stages. Initially, preventive treatment was implemented, with fluoride varnish applications, in order to protect the fragile enamel and reduce the dental sensitivity. In the second stage, the patient received an interceptive orthopedic treatment to improve cross-relationship of the arches during six months. Finally, the rehabilitation treatment was executed to establish the vertical dimension. In the posterior teeth, indirect composite resin crowns were performed with minimally invasive dental preparation. Direct composite resin restorations were used to improve the appearance of anterior teeth. Follow-Up. The follow-up was carried out after 3, 6, 12, and 18 months. After 18 months of follow-up, The restoration of integrity, oral hygiene, and patient satisfaction were observed . Conclusion. Successful reduction of the dental hypersensitivity and improvement of the aesthetic and functional aspects as well as quality of life were observed. PMID:25061528

  7. De novo mutation in the DSPP gene associated with dentinogenesis imperfecta type II in a Japanese family.

    Science.gov (United States)

    Kida, Miyuki; Tsutsumi, Tomonori; Shindoh, Masanobu; Ikeda, Hisami; Ariga, Tadashi

    2009-12-01

    Dentinogenesis imperfecta (DGI) type II is one of the most common dominantly inherited dentin defects, in which both the primary and permanent teeth are affected. Here, we report a Japanese family with autosomal-dominant DGI type II, including both molecular genetic defects and pathogenesis with histological analysis. Mutation analysis revealed a mutation (c.53T>A, p.V18D, g.1192T>A) involving the second nucleotide of the first codon within exon 3 of the dentin sialophosphoprotein (DSPP) gene. This mutation has previously been reported in a Korean family. Thus far, 24 allelic DSPP mutations have been reported, and this is the seventh mutation involving the DSPP V18 residue. Among those, only one other was shown to be caused by a de novo mutation, and that mutation also affected the V18 amino acid residue. The DSPP V18 residue is highly conserved among other mammalian species. These findings thus suggest that the V18 amino acid might be a sensitive mutational hot spot, playing a critical role in the pathogenesis of DGI.

  8. Noninvasive and Multidisciplinary Approach to the Functional and Esthetic Rehabilitation of Amelogenesis Imperfecta: A Pediatric Case Report

    Directory of Open Access Journals (Sweden)

    Juliana Feltrin de Souza

    2014-01-01

    Full Text Available Case Report. An 8-year-old girl with amelogenesis imperfecta (AI reported unsatisfactory aesthetics, difficulty in mastication, and dental hypersensitivity. The intraoral examination observed mixed dentition, malocclusion in anteroposterior relationships, anterior open bite, and dental asymmetry. A hypoplastic form of AI was diagnosed in the permanent dentition. A multidisciplinary planning was performed and divided into preventive, orthopedic, and rehabilitation stages. Initially, preventive treatment was implemented, with fluoride varnish applications, in order to protect the fragile enamel and reduce the dental sensitivity. In the second stage, the patient received an interceptive orthopedic treatment to improve cross-relationship of the arches during six months. Finally, the rehabilitation treatment was executed to establish the vertical dimension. In the posterior teeth, indirect composite resin crowns were performed with minimally invasive dental preparation. Direct composite resin restorations were used to improve the appearance of anterior teeth. Follow-Up. The follow-up was carried out after 3, 6, 12, and 18 months. After 18 months of follow-up, The restoration of integrity, oral hygiene, and patient satisfaction were observed . Conclusion. Successful reduction of the dental hypersensitivity and improvement of the aesthetic and functional aspects as well as quality of life were observed.

  9. Amelogenesis Imperfecta and Early Restorative Crown Therapy: An Interview Study with Adolescents and Young Adults on Their Experiences.

    Directory of Open Access Journals (Sweden)

    Gunilla Pousette Lundgren

    Full Text Available Patients with Amelogenesis imperfecta (AI can present with rapid tooth loss or fractures of enamel as well as alterations in enamel thickness, color, and shape; factors that may compromise aesthetic appearance and masticatory function. The aim was to explore the experiences and perceptions of adolescents and young adults living with AI and receiving early prosthetic therapy. Seven patients with severe AI aged 16 to 23 years who underwent porcelain crown therapy participated in one-to-one individual interviews. The interviews followed a topic guide consisting of open-ended questions related to experiences of having AI. Transcripts from the interviews were analyzed using thematic analysis. The analysis process identified three main themes: Disturbances in daily life, Managing disturbances, and Normalization of daily life. These themes explain the experiences of patients living with enamel disturbances caused by AI and receiving early crown therapy. Experiences include severe pain and sensitivity problems, feelings of embarrassment, and dealing with dental staff that lack knowledge and understanding of their condition. The patients described ways to manage their disturbances and to reduce pain when eating or drinking, and strategies for meeting other people. After definitive treatment with porcelain crown therapy, they described feeling like a normal patient. In conclusion the results showed that adolescents and young adults describe a profound effect of AI on several aspects of their daily life.

  10. Amelogenesis Imperfecta and Early Restorative Crown Therapy: An Interview Study with Adolescents and Young Adults on Their Experiences

    Science.gov (United States)

    Wickström, Anette; Hasselblad, Tove; Dahllöf, Göran

    2016-01-01

    Patients with Amelogenesis imperfecta (AI) can present with rapid tooth loss or fractures of enamel as well as alterations in enamel thickness, color, and shape; factors that may compromise aesthetic appearance and masticatory function. The aim was to explore the experiences and perceptions of adolescents and young adults living with AI and receiving early prosthetic therapy. Seven patients with severe AI aged 16 to 23 years who underwent porcelain crown therapy participated in one-to-one individual interviews. The interviews followed a topic guide consisting of open-ended questions related to experiences of having AI. Transcripts from the interviews were analyzed using thematic analysis. The analysis process identified three main themes: Disturbances in daily life, Managing disturbances, and Normalization of daily life. These themes explain the experiences of patients living with enamel disturbances caused by AI and receiving early crown therapy. Experiences include severe pain and sensitivity problems, feelings of embarrassment, and dealing with dental staff that lack knowledge and understanding of their condition. The patients described ways to manage their disturbances and to reduce pain when eating or drinking, and strategies for meeting other people. After definitive treatment with porcelain crown therapy, they described feeling like a normal patient. In conclusion the results showed that adolescents and young adults describe a profound effect of AI on several aspects of their daily life. PMID:27359125

  11. An investigation on clinical radiological diagnosis of hereditary osteogenesis imperfect (a report of 42 patients in a family)

    International Nuclear Information System (INIS)

    Purpose: To investigate the main points of diagnosing hereditary osteogenesis imperfect. Methods: Retrospective analysis of clinical and radiological diagnosis of hereditary osteogenesis imperfect was done in 35 surviving patients and 7 deaths in a family. Results: (1) A family was described in which hereditary osteogenesis imperfect occurred in 5 generations. Forty-two patients (18 males, 24 females) ranged in age from 10 months to 67 years. (2) Both modes of inheritance existed simultaneously (dominant in 35 patients, recessive in 7 patients). (3) Blue sclera of different shades was found in all 42 patients. (4) Radiological change of bone was recognised in 35 surviving patients. The conditions were as follows: in 29 patients, general decreased bone density, thin bone cortex and long slender tubular bones were observed; six patients were normal; twenty-two patients had fracture. (5) Twenty-four patients (including 3 deaths) suffered form progressive deafness. (6) Twenty-one patients (including 3 deaths) had the triad of blue sclera, osteopsathyrosis and progressive deafness. (7) An increase in alkaline phosphatase level (in 17 patients) was confirmed by the tests in our laboratory. Conclusion: The authors suggested that the triad of blue sclera, osteopsathyrosis and progressive deafness is the characteristic manifestations of the disease, especially blue sclera, which may be regarded as an initial and suggestible physical sign, and an essential criterion for diagnosis

  12. Focal Adhesion Kinase Signaling Mediated the Enhancement of Osteogenesis of Human Mesenchymal Stem Cells Induced by Extracorporeal Shockwave

    Science.gov (United States)

    Hu, Jun; Liao, Haojie; Ma, Zebin; Chen, Hongjiang; Huang, Zhonglian; Zhang, Yuantao; Yu, Menglei; Chen, Youbin; Xu, Jiankun

    2016-02-01

    Extracorporeal shockwave (ESW) has been shown of great potential in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but it is unknown whether this osteogenic promotion effect can also be achieved in other MSCs (i.e., tendon-derived stem cells (TDSCs) and adipose-derived stem cells (ADSCs)). In the current study, we aimed not only to compare the osteogenic effects of BMSCs induced by ESW to those of TDSCs and ADSCs; but also to investigate the underlying mechanisms. We show here that ESW (0.16 mj/mm2) significantly promoted the osteogenic differentiation in all the tested types of MSCs, accompanied with the downregulation of miR-138, but the activation of FAK, ERK1/2, and RUNX2. The enhancement of osteogenesis in these MSCs was consistently abolished when the cells were pretreated with one of the following conditions: overexpression of miR-138, FAK knockdown using specific siRNA, and U0126, implying that all of these elements are indispensable for mediating the effect of ESW. Moreover, our study provides converging genetic and molecular evidence that the miR-138-FAK-ERK1/2-RUNX2 machinery can be generally activated in ESW-preconditioned MSCs, suggesting that ESW may be a promising therapeutic strategy for the enhancement of osteogenesis of MSCs, regardless of their origins.

  13. Expression of Neurotrophins and Their Receptors Tropomyosin-related kinases (Trk under Tension-stress during Distraction Osteogenesis

    Directory of Open Access Journals (Sweden)

    Aiga,Ayako

    2006-10-01

    Full Text Available The localization and expression of neurotrophins and their receptors during distraction osteogenesis was investigated in 72 male rat femurs (11 weeks old to further clarify the concurrence of cellular and molecular events of new bone formation. After osteotomy, a 7-day lag phase was followed by distraction at the rate of 0.25 mm/12 h for 21 days (distraction phase, and a 7-day consolidation phase. The localization of neurotrophins (NGF, BDNF and NT-3 and their receptors tropomyosinrelated kinases (TRKA, TRKB and TRKC by immunostaining showed positive staining in bone forming cells in each stage, although the presence and staining intensity varied by cell type and phase. The expressions of NGF, BDNF and NT-3 by real-time polymerase chain reaction (real-time PCR showed that the peak of the mRNA expression of NGF occurred 10 days after distraction. NT-3 increased during bone extension, but decreased when distraction stopped. In contrast, BDNF continued to increase gradually throughout the distraction and consolidation phases. These findings suggest that neurotrophins and their receptors may play different roles in endochondral and intramembranous ossification in distraction osteogenesis. The tension stress caused by distraction may stimulate the expression of neurotrophins and their receptors, and promote osteogenesis.

  14. Melatonin reversed tumor necrosis factor-alpha-inhibited osteogenesis of human mesenchymal stem cells by stabilizing SMAD1 protein.

    Science.gov (United States)

    Lian, Chengjie; Wu, Zizhao; Gao, Bo; Peng, Yan; Liang, Anjing; Xu, Caixia; Liu, Lei; Qiu, Xianjian; Huang, Junjun; Zhou, Hang; Cai, Yifeng; Su, Peiqiang; Huang, Dongsheng

    2016-10-01

    Tumor necrosis factor-alpha (TNFα) plays a pivotal role in inflammation-related osteoporosis through the promotion of bone resorption and suppression of bone formation. Numerous drugs have been produced to treat osteoporosis by inhibiting bone resorption, but they offer few benefits to bone formation, which is what is needed by patients with severe bone loss. Melatonin, which can exert both anti-inflammatory and pro-osteogenic effects, shows promise in overcoming TNFα-inhibited osteogenesis and deserves further research. This study demonstrated that melatonin rescued TNFα-inhibited osteogenesis of human mesenchymal stem cells and that the interactions between SMURF1 and SMAD1 mediated the crosstalk between melatonin signaling and TNFα signaling. Additionally, melatonin treatment was found to downregulate TNFα-induced SMURF1 expression and then decrease SMURF1-mediated ubiquitination and degradation of SMAD1 protein, leading to steady bone morphogenetic protein-SMAD1 signaling activity and restoration of TNFα-impaired osteogenesis. Thus, melatonin has prospects for treating osteoporosis caused by inflammatory factors due to its multifaceted functions on regulation of bone formation, bone resorption, and inflammation. Further studies will focus on unveiling the specific mechanisms by which melatonin downregulates SMURF1 expression and confirming the clinical therapeutic value of melatonin in the prevention and therapy of bone loss associated with inflammation. PMID:27265199

  15. Influence of co-culture on osteogenesis and angiogenesis of bone marrow mesenchymal stem cells and aortic endothelial cells.

    Science.gov (United States)

    Gurel Pekozer, Gorke; Torun Kose, Gamze; Hasirci, Vasif

    2016-11-01

    Co-culture of bone forming cells and endothelial cells to induce pre-vascularization is one of the strategies used to solve the insufficient vascularization problem in bone tissue engineering attempts. In the study, primary cells isolated from 2 different tissues of the same animal, rat bone marrow stem cells (RBMSCs) and rat aortic endothelial cells (RAECs) were co-cultured to study the effects of co-culturing on both osteogenesis and angiogenesis. The formation of tube like structure in 2D culture was observed for the first time in the literature by the co-culture of primary cells from the same animal and also osteogenesis and angiogenesis were investigated at the same time by using this co-culture system. Co-cultured cells mineralized and formed microvasculature beginning from 14days of incubation. After 28days of incubation in the osteogenic medium, expression of osteogenic genes in co-cultures was significantly upregulated compared to RBMSCs cultured alone. These results suggest that the co-culture of endothelial cells with mesenchymal stem cells induces both osteogenesis and angiogenesis.

  16. Effects of γ-secretase inhibition on the proliferation and vitamin D3 induced osteogenesis in adipose derived stem cells

    International Nuclear Information System (INIS)

    As a γ-secretase inhibitor, DAPT has been widely used to evaluate the biological behaviors and Notch signaling pathway in various cells. This study was aimed to examine the effects of DAPT on the growth and vitamin D3 induced osteogenesis in adipose derived stem cells (ASCs). The cells were treated with or without DAPT and induced to osteoblastic lineage in the presence of vitamin D3. Alizarin red staining and real-time PCR results indicated that the addition of DAPT to vitamin D3 treatments enhanced osteogenesis in ASCs. According to the fold increase and colony-forming unit assay results, the cells cultured in DAPT exhibited lower proliferation rate than those cultured in control medium. Hey1, expressed in the nucleus of ASCs to act as a transcriptional repressor, was downregulated when Notch signaling was inhibited by DAPT. Whereas the expression of Runx2 increased in the nucleus of osteogenic induced ASCs after DAPT treatment. This study demonstrated that DAPT reduced the proliferation and enhanced the osteogenesis in ASCs via regulation of Notch and Runx2 expression.

  17. Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta.

    Science.gov (United States)

    Parry, David A; Brookes, Steven J; Logan, Clare V; Poulter, James A; El-Sayed, Walid; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Sayed, Jihad; Raïf, El Mostafa; Shore, Roger C; Dashash, Mayssoon; Barron, Martin; Morgan, Joanne E; Carr, Ian M; Taylor, Graham R; Johnson, Colin A; Aldred, Michael J; Dixon, Michael J; Wright, J Tim; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2012-09-01

    Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis.

  18. Enhancement of osteogenesis on micro/nano-topographical carbon fiber-reinforced polyetheretherketone–nanohydroxyapatite biocomposite

    International Nuclear Information System (INIS)

    As an FDA-approved implantable material, carbon fiber-reinforced polyetheretherketone (CFRPEEK) possesses excellent mechanical properties similar to those of human cortical bone and is a prime candidate to replace conventional metallic implants. The bioinertness and inferior osteogenic properties of CFRPEEK, however, limit its clinical application as orthopedic/dental implants. The present work aimed at developing a novel carbon fiber-reinforced polyetheretherketone–nanohydroxyapatite (PEEK/CF/n-HA) ternary biocomposite with micro/nano-topographical surface for the enhancement of the osteogenesis as a potential bioactive material for bone grafting and bone tissue-engineering applications. The combined modification of oxygen plasma and sand-blasting could improve the hydrophily and generate micro/nano-topographical structures on the surface of the CFRPEEK-based ternary biocomposite. The results clearly showcased that the micro-/nano-topographical PEEK/n-HA/CF ternary biocomposite demonstrated the outstanding ability to promote the proliferation and differentiation of MG-63 cells in vitro as well as to boost the osseointegration between implant and bone in vivo, thereby boding well application to bone tissue engineering. - Highlights: • A novel micro/nano-topographical PEEK/n-HA/CF ternary biocomposite was developed. • The modified PEEK biocomposite promotes proliferation and differentiation of cells. • In vivo osseointegration of the micro/nano-topographical PEEK/n-HA/CF was enhanced

  19. Experimental Research on Ectopic Osteogenesis of BMP2-derived Peptide P24 Combined with PLGA Copolymers

    Institute of Scientific and Technical Information of China (English)

    DUAN Zhixia; ZHENG Qixin; GUO Xiaodong; YUAN Quan; CHEN Shunguang

    2007-01-01

    To experimentally evaluate the ectopic osteogenetic capacity of synthesized BMP2-derived peptide P24 combined with poly lactic-co-glycolic acid (PLGA), Wistar rats were divided into two groups: group A, in which BMP2-derived peptide P24/PLGA complex was implanted,and group B which received simple PLGA implant. The complex was respectively implanted into the back muscles of rats. Samples were taken the 1 st, 4 th, 8 th, and the 12 th week after the implantation.Their bone formation was detected by X-ray examination, and tissue response was histologically observed. Western blotting was used for the detection of the expression of collagen Ⅰ (Col- Ⅰ ) and osteopontin (OPN). There was acute inflammation in the tissue around both types of implants at early stage. The cartilage was found around implant areas 4 weeks after the implantation of BMP2-derived peptide p24/PLGA complex, 8 weeks after the implantation, osteoblasts were found, and 12 weeks after the implantation, typical trabecular bone structure was observed. In group B, after 12 weeks, no osteoblasts were found. It is concluded that PLGA is an ideal scaffold material for bone tissue engineering. BMP2-derived peptide can start endochondral ossification and is more effective in inducing ectopic osteogenesis.

  20. Severe proliferative congenital temporomandibular joint ankylosis: a proposed treatment protocol utilizing distraction osteogenesis.

    Science.gov (United States)

    Bartlett, Scott P; Reid, Russell R; Losee, Joseph E; Quinn, Peter D

    2006-05-01

    The classical treatment for temporomandibular joint (TMJ) ankylosis in children: 1) joint release; 2) arthroplasty; 3) reconstruction; and 4) postoperative physical therapy (PT), is often unsuccessful. Postoperative physical therapy is difficult in the young patient due to poor cooperation. Moreover, there is a subgroup of patients who have a refractory congenital proliferative bony process that is the cause of their disease. In these patients, a role for distraction osteogenesis (DO) has been defined. We present a series of young patients with congenital proliferative TMJ ankylosis. Some have failed classic treatment. In such cases, DO is used to expand the mandibular size and soft tissue matrix. This creates a static open bite, facilitates mid-facial growth, and avoids compromise of the airway, speech, nutrition, and oral hygiene. To maintain these objectives, mandibular DO may be repeated as the child matures. Once skeletal maturity is reached, DO is used to normalize occlusion and further expand the soft tissue envelope prior to definitive reconstruction and aggressive post-op PT. In seven patients, this protocol has been used. Five patients are currently in the active phase of growth and undergoing interim treatment with mandibular DO. Two patients have reached skeletal maturity and have completed the protocol of DO with definitive arthroplasty and reconstruction. DO is a valuable aid in the treatment of the problematic child with congenital proliferative TMJ ankylosis. Interim DO, prior to definitive arthroplasty and reconstruction, can provide a static open bite that prevents progressive deformity and its associated functional disturbances. PMID:16770209