Retinoic receptor signaling regulates hypertrophic chondrocyte-specific gene expression
PublisherInternational Institute of Anticancer Research
MetadataShow full item record
AbstractBackground/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.
SponsorsThis 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.).
Connective tissue growth factor
Mitogen-activated protein kinase
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85059241113&doi=10.21873%2finvivo.11443&partnerID=40&md5=1d651612dca7f40c3f284285cc28165e; http://hdl.handle.net/10713/10750
- Retinoid signaling regulates CTGF expression in hypertrophic chondrocytes with differential involvement of MAP kinases.
- Authors: Shimo T, Koyama E, Sugito H, Wu C, Shimo S, Pacifici M
- Issue date: 2005 May
- Expression and Role of IL-1β Signaling in Chondrocytes Associated with Retinoid Signaling during Fracture Healing.
- Authors: Shimo T, Takebe H, Okui T, Kunisada Y, Ibaragi S, Obata K, Kurio N, Shamsoon K, Fujii S, Hosoya A, Irie K, Sasaki A, Iwamoto M
- Issue date: 2020 Mar 29
- Retinoid signaling is required for chondrocyte maturation and endochondral bone formation during limb skeletogenesis.
- Authors: Koyama E, Golden EB, Kirsch T, Adams SL, Chandraratna RA, Michaille JJ, Pacifici M
- Issue date: 1999 Apr 15
- A novel role for GADD45beta as a mediator of MMP-13 gene expression during chondrocyte terminal differentiation.
- Authors: Ijiri K, Zerbini LF, Peng H, Correa RG, Lu B, Walsh N, Zhao Y, Taniguchi N, Huang XL, Otu H, Wang H, Wang JF, Komiya S, Ducy P, Rahman MU, Flavell RA, Gravallese EM, Oettgen P, Libermann TA, Goldring MB
- Issue date: 2005 Nov 18
- GADD45beta enhances Col10a1 transcription via the MTK1/MKK3/6/p38 axis and activation of C/EBPbeta-TAD4 in terminally differentiating chondrocytes.
- Authors: Tsuchimochi K, Otero M, Dragomir CL, Plumb DA, Zerbini LF, Libermann TA, Marcu KB, Komiya S, Ijiri K, Goldring MB
- Issue date: 2010 Mar 12