Id2 controls chondrogenesis acting downstream of BMP signaling during maxillary morphogenesis

Tomoko Sakata-Goto, Katsu Takahashi, Honoka Kiso, Boyen Huang, Hiroko Tsukamoto, Mitsuru Takemoto, Tatsunari Hayashi, Manabu Sugai, Takashi Nakamura, Yoshifumi Yokota, Akira Shimizu, Harold Slavkin, Kazuhisa Bessho

Research output: Contribution to journalArticlepeer-review

Abstract

Maxillofacial dysmorphogenesis is found in 5% of the population. To begin to understand the mechanisms required for maxillofacial morphogenesis, we employed the inhibitors of the differentiation 2 (Id2) knock-out mouse model, in which Id proteins, members of the regulator of basic helix-loop-helix (bHLH) transcription factors, modulate cell proliferation, apoptosis, and differentiation.We now report that spatially-restricted growth defects are localized at the skull base of Id2 KO mice. Curiously, at birth, neither the mutant Id2 KO nor wild-type (WT) mice differed, based upon cephalometric and histological analyses of cranial base synchondroses. In postnatal week 2, a narrower hypertrophic zone and an inhibited proliferative zone in presphenoid synchondrosis (PSS) and spheno-occipital synchondrosis (SOS) with maxillary hypoplasia were identified in the Id2 mutant mice. Complementary studies revealed that exogenous bone morphogenetic proteins (BMPs) enhanced cartilage growth, matrix deposition, and chondrocyte proliferation in the WT but not in the mutant model. Id2-deficient chondrocytes expressed more Smad7 transcripts.Based on our results, we assert that Id2 plays an essential role, acting downstream of BMP signaling, to regulate cartilage formation at the postnatal stage by enhancing BMP signals through inhibiting Smad7 expression. As a consequence, abnormal endochondral ossification was observed in cranial base synchondroses during the postnatal growth period, resulting in the clinical phenotype of maxillofacial dysmorphogenesis.

Original languageEnglish (US)
Pages (from-to)69-78
Number of pages10
JournalBone
Volume50
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by a Grant-in-Aid for Young Scientists (B) from the Japanese Society for the Promotion of Science . We thank the all members of Translation Research Center (Kyoto University Hospital) for the great technical support and discussions in this study.

Keywords

  • BMP
  • Id2
  • Jaw deformity
  • Smad7
  • Synchondrosis

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