Id2 controls chondrogenesis acting downstream of BMP signaling during maxillary morphogenesis
Sakata-Goto, Tomoko, Takahashi, Katsu, Kiso, Honoka, Huang, Boyen, Tsukamoto, Hiroko, Takemoto, Mitsuru, Hayashi, Tatsunari, Sugai, Manabu, Nakamura, Takashi, Yokota, Yoshifumi, Shimizu, Akira, Slavkin, Harold, and Bessho, Kazuhisa (2012) Id2 controls chondrogenesis acting downstream of BMP signaling during maxillary morphogenesis. Bone, 50 (1). pp. 69-78.
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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.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||Id2; synchondrosis; BMP; Smad7; jaw deformity|
|Date Deposited:||26 Sep 2012 02:55|
|FoR Codes:||06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060111 Signal Transduction @ 30%
06 BIOLOGICAL SCIENCES > 0604 Genetics > 060403 Developmental Genetics (incl Sex Determination) @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1105 Dentistry > 110504 Oral and Maxillofacial Surgery @ 30%
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920110 Inherited Diseases (incl. Gene Therapy) @ 30%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920116 Skeletal System and Disorders (incl. Arthritis) @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920113 Oro-Dental Disorders @ 20%