Delayed osteoprogenitor differentiation in cleft-palate models.
Failure of palatal shelf fusion results in cleft palate (CP) and may lead to malformation of palatal bones and undergrowth of the maxilla. It is not known whether defects in bone formation may contribute to this phenotype. We tested the hypothesis that impaired fusion of developing palatal shelves affects palatal bone development using palate organotypic cultures. Using two different approaches, we show that induction of cleft results in increased expression of pre-osteoblast and early osteoblast markers, Twist1, Snai1 and Runx2, and decreased expression of more mature markers of bone differentiation, collagen-1 and osteopontin, indicating delayed osteoblast differentiation in CPs. This, together with the increase in immature osteoblasts and proliferation observed in non-fused palatal shelves, suggests that palatal osteoblast differentiation is at least partly modulated by shelf fusion. Delayed osteoblast differentiation may therefore contribute to defects in gross morphology and function of the maxilla in CP patients.
Pungchanchaikul
P
P
UCL Institute of Child Health, London, UK.
Bloch-Zupan
A
A
Ferretti
P
P
D000818:Animals; D001846:Bone Development / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002972:Cleft Palate / Q000196:embryology*; D024042:Collagen Type I / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D004195:Disease Models, Animal; D005147:Facial Bones / Q000196:embryology; D015870:Gene Expression; D008445:Maxillofacial Development / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D053495:Osteopontin / Q000235:genetics; D010159:Palate / Q000196:embryology; D010160:Palate, Soft / Q000196:embryology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology; D051879:Twist-Related Protein 1 / Q000235:genetics
D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D009687:Nuclear Proteins; C493716:Runx2 protein, mouse; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051879:Twist-Related Protein 1; D053495:Osteopontin; C067250:Twist1 protein, mouse