Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 85-91 |
| Number of pages | 7 |
| Journal | In vivo (Athens, Greece) |
| Volume | 33 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- chondrocyte maturation
- connective tissue growth factor
- matrix metalloproteinase
- mitogen-activated protein kinase
- Retinoid signaling
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology
Cite this
Retinoic Receptor Signaling Regulates Hypertrophic Chondrocyte-specific Gene Expression. / Shimo, Tsuyoshi; Koyama, Eiki; Okui, Tatsuo; Masui, Masanori; Kunisada, Yuki; Ibaragi, Soichiro; Yoshioka, Norie; Kurio, Naito; Yoshida, Shoko; Sasaki, Akira; Iwamoto, Masahiro.
In: In vivo (Athens, Greece), Vol. 33, No. 1, 01.01.2019, p. 85-91.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Retinoic Receptor Signaling Regulates Hypertrophic Chondrocyte-specific Gene Expression
AU - Shimo, Tsuyoshi
AU - Koyama, Eiki
AU - Okui, Tatsuo
AU - Masui, Masanori
AU - Kunisada, Yuki
AU - Ibaragi, Soichiro
AU - Yoshioka, Norie
AU - Kurio, Naito
AU - Yoshida, Shoko
AU - Sasaki, Akira
AU - Iwamoto, Masahiro
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - chondrocyte maturation
KW - connective tissue growth factor
KW - matrix metalloproteinase
KW - mitogen-activated protein kinase
KW - Retinoid signaling
UR - http://www.scopus.com/inward/record.url?scp=85059241113&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059241113&partnerID=8YFLogxK
U2 - 10.21873/invivo.11443
DO - 10.21873/invivo.11443
M3 - Article
VL - 33
SP - 85
EP - 91
JO - In Vivo
JF - In Vivo
SN - 0258-851X
IS - 1
ER -