TY - JOUR
T1 - Id2 controls chondrogenesis acting downstream of BMP signaling during maxillary morphogenesis
AU - Sakata-Goto, Tomoko
AU - Takahashi, Katsu
AU - Kiso, Honoka
AU - Huang, Boyen
AU - Tsukamoto, Hiroko
AU - Takemoto, Mitsuru
AU - Hayashi, Tatsunari
AU - Sugai, Manabu
AU - Nakamura, Takashi
AU - Yokota, Yoshifumi
AU - Shimizu, Akira
AU - Slavkin, Harold
AU - Bessho, Kazuhisa
N1 - 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.
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - BMP
KW - Id2
KW - Jaw deformity
KW - Smad7
KW - Synchondrosis
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U2 - 10.1016/j.bone.2011.09.049
DO - 10.1016/j.bone.2011.09.049
M3 - Article
C2 - 21985998
AN - SCOPUS:80054727326
SN - 8756-3282
VL - 50
SP - 69
EP - 78
JO - Bone
JF - Bone
IS - 1
ER -