Enhanced BMP signaling leads to enlarged nasal cartilage formation in mice.
Biochem Biophys Res Commun
; 678: 173-178, 2023 10 20.
Article
em En
| MEDLINE
| ID: mdl-37640003
ABSTRACT
Bone morphogenetic proteins (BMPs) are required for craniofacial bone development. However, it remains elusive how BMP signaling regulates craniofacial cartilage development. To address this question, we utilized a genetic system to enhance BMP signaling via one of BMP type I receptors ALK2 in a chondrocyte-specific manner (hereafter Ca-Alk2Col2-Cre) in mice. Ca-Alk2Col2-Cre mice died shortly after birth due to severe craniofacial abnormalities including cleft palate, defective tongue, and shorter mandible formation. Histological analysis revealed that these phenotypes were attributed to the extensive chondrogenesis. Compared with controls, enhanced SOX9 and RUNX2 production were observed in nasal cartilage of Ca-Alk2Col2-Cre mice. To reveal the mechanisms responsible for enlarged nasal cartilage, we examined Smad-dependent and Smad-independent BMP signaling pathways. While the Smad-independent BMP signaling pathway including p38, ERK, and JNK remained silent, the Smad1/5/9 was highly phosphorylated in Ca-Alk2Col2-Cre mice. Interestingly, Ca-Alk2Col2-Cre mice showed enhanced S6 kinase phosphorylation, a readout of mammalian target of rapamycin complex 1 (mTORC1). These findings may suggest that enhanced Smad-dependent BMP signaling positively regulates the mTOR pathway and stimulates chondrocytes toward hypertrophic differentiation, thereby leading to enlarged nasal cartilage formation in mice.
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Base de dados:
MEDLINE
Assunto principal:
Fissura Palatina
/
Cartilagens Nasais
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article