ATRA Signaling Regulates the Expression of COL9A1 through BMP2-WNT4-RUNX1 Pathway in Antler Chondrocytes
| Autor: | Kai Wang, Zhan-Qing Yang, Hong-Liang Zhang, Hai-Fan Yu, Bin Guo, Cui-Cui Duan, Shuang Geng, Zhan-Peng Yue |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
animal structures Retinoic acid Biology Bone morphogenetic protein 2 03 medical and health sciences chemistry.chemical_compound CYP26A1 0302 clinical medicine Downregulation and upregulation WNT4 Genetics Gene silencing neoplasms Transcription factor Ecology Evolution Behavior and Systematics Gene knockdown organic chemicals Molecular biology biological factors Cell biology 030104 developmental biology chemistry 030220 oncology & carcinogenesis embryonic structures Molecular Medicine Animal Science and Zoology Developmental Biology |
| Zdroj: | Journal of Experimental Zoology Part B: Molecular and Developmental Evolution. 328:575-586 |
| ISSN: | 1552-5007 |
| DOI: | 10.1002/jez.b.22756 |
| Popis: | Although all-trans retinoic acid (ATRA) is involved in the regulation of cartilage growth and development, its regulatory mechanisms remain unknown. Here, we showed that ATRA could induce the expression of COL9A1 in antler chondrocytes. Silencing of cellular retinoic acid binding protein 2 (CRABP2) could impede the ATRA-induced upregulation of COL9A1, whereas overexpression of CRABP2 presented the opposite effect. RARα agonist Am80 induced the expression of COL9A1, whereas treatment with RARα antagonist Ro 41-5253 or RXRα small-interfering RNA (siRNA) caused an obvious blockage of ATRA on COL9A1. In antler chondrocytes, CYP26A1 and CYP26B1 weakened the sensitivity of ATRA to COL9A1. Simultaneously, Bone morphogenetic protein 2 (BMP2) and WNT4 mediated the regulation of ATRA on COL9A1 expression. Knockdown of WNT4 could abrogate the inhibitory effect of BMP2 overexpression on COL9A1. Conversely, constitutive expression of WNT4 reversed the upregulation of COL9A1 elicited by BMP2 siRNA. Together these data indicated that WNT4 might act downstream of BMP2 to mediate the effect of ATRA on COL9A1 expression. Further analysis evidenced that attenuation of runt-related transcription factor 1 (RUNX1) could prevent the stimulation of ATRA on COL9A1 expression, while exogenous rRUNX1 further enhanced this effectiveness. Moreover, RUNX1 might serve as an intermediate to mediate the regulation of BMP2 and WNT4 on COL9A1 expression. Collectively, ATRA signaling might regulate the expression of COL9A1 through BMP2-WNT4-RUNX1 pathway. |
| Databáze: | OpenAIRE |
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