Retinoic receptor signaling regulates hypertrophic chondrocyte-specific gene expression
Date
2019Journal
In VivoPublisher
International Institute of Anticancer ResearchType
Article
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Background/Aim: Retinoid signaling is important for the maturation of growth-plate chondrocytes. The effect of retinoid receptor gamma (RARγ) signaling on the expression of genes in hypertrophic chondrocytes is unclear. This study investigated the role of RARγ signaling in regulation of hypertrophic chondrocyte-specific genes. Materials and Methods: The gene expression in mouse E17.5 tibial cartilage was examined by in situ hybridization analysis. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting were used for analysis of mRNA and phosphorylated mitogen-activated protein kinase (MAPK). Results: mRNA expression of Rarg and connective tissue growth factor (Ccn2) was detected in maturing chondrocytes throughout the cartilaginous skeletal elements. In chondrogenic ATDC5 cells, an RARγ agonist induced the gene expression of type-X collagen (Col10A1), transglutaminase-2 (Tg2), matrix metalloproteinase-13 (Mmp13), and Ccn2 mRNA, whereas a retinoic acid pan-agonist suppressed RARγ agonist-stimulated gene expression. Phosphorylated extracellular signal regulated-kinases (pERK1/2), p-p38, and phosphorylated c-Jun N-terminal kinase (pJNK) MAPK were time-dependently increased by RARγ agonist treatment. Experimental p38 inhibition led to a severe drop in the RARγ agonist-stimulated expressions of Col10A1, Tg2, Mmp13, and Ccn2 mRNA. Conclusion: RARγ signaling is required for the differentiation of hypertrophic chondrocytes, with differential cooperation with p38 MAPK.Sponsors
This work was partly supported by a Grant-in-Aid for Scientific Research (B) #JP18H02999 (T.S.) from Japan Society for the promotion of Sciences, Japan and the NIH AR05683 (M.I.) and NIH AR072713 (M.I.).Keyword
Chondrocyte maturationConnective tissue growth factor
Matrix metalloproteinase
Mitogen-activated protein kinase
Retinoid signaling
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85059241113&doi=10.21873%2finvivo.11443&partnerID=40&md5=1d651612dca7f40c3f284285cc28165e; http://hdl.handle.net/10713/10750ae974a485f413a2113503eed53cd6c53
10.21873/invivo.11443
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