| RRC ID |
37701
|
| 著者 |
Amano K, Hata K, Sugita A, Takigawa Y, Ono K, Wakabayashi M, Kogo M, Nishimura R, Yoneda T.
|
| タイトル |
Sox9 family members negatively regulate maturation and calcification of chondrocytes through up-regulation of parathyroid hormone-related protein.
|
| ジャーナル |
Mol Biol Cell
|
| Abstract |
Sox9 is a transcription factor that plays an essential role in chondrogenesis and has been proposed to inhibit the late stages of endochondral ossification. However, the molecular mechanisms underlying the regulation of chondrocyte maturation and calcification by Sox9 remain unknown. In this study, we attempted to clarify roles of Sox9 in the late stages of chondrocyte differentiation. We found that overexpression of Sox9 alone or Sox9 together with Sox5 and Sox6 (Sox5/6/9) inhibited the maturation and calcification of murine primary chondrocytes and up-regulated parathyroid hormone-related protein (PTHrP) expression in primary chondrocytes and the mesenchymal cell line C3H10T1/2. Sox5/6/9 stimulated the early stages of chondrocyte proliferation and development. In contrast, Sox5/6/9 inhibited maturation and calcification of chondrocytes in organ culture. The inhibitory effects of Sox5/6/9 were rescued by treating with anti-PTHrP antibody. Moreover, Sox5/6/9 bound to the promoter region of the PTHrP gene and up-regulated PTHrP gene promoter activity. Interestingly, we also found that the Sox9 family members functionally collaborated with Ihh/Gli2 signaling to regulate PTHrP expression and chondrocyte differentiation. Our results provide novel evidence that Sox9 family members mediate endochondral ossification by up-regulating PTHrP expression in association with Ihh/Gli2 signaling.
|
| 巻・号 |
20(21)
|
| ページ |
4541-51
|
| 公開日 |
2009-11-1
|
| DOI |
10.1091/mbc.e09-03-0227
|
| PII |
E09-03-0227
|
| PMID |
19759178
|
| PMC |
PMC2770942
|
| MeSH |
Animals
Calcification, Physiologic*
Cell Differentiation / physiology*
Cell Line
Chondrocytes / cytology
Chondrocytes / physiology*
Chondrogenesis / physiology*
Hedgehog Proteins / genetics
Hedgehog Proteins / metabolism
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / metabolism
Mice
Parathyroid Hormone-Related Protein / genetics
Parathyroid Hormone-Related Protein / metabolism*
SOX9 Transcription Factor / genetics
SOX9 Transcription Factor / metabolism*
SOXD Transcription Factors / genetics
SOXD Transcription Factors / metabolism
Signal Transduction / physiology
Tissue Culture Techniques
Zinc Finger Protein Gli2
|
| IF |
3.791
|
| 引用数 |
48
|
|
WOS 分野
|
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
10T1/2(RCB0247)
COS-7(RCB0539) |
