Retinoic Receptor Signaling Regulates Hypertrophic Chondrocyte-specific Gene Expression

Tsuyoshi Shimo, Eiki Koyama, Tatsuo Okui, Masanori Masui, Yuki Kunisada, Soichiro Ibaragi, Norie Yoshioka, Naito Kurio, Shoko Yoshida, Akira Sasaki, Masahiro Iwamoto

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)85-91
Number of pages7
JournalIn vivo (Athens, Greece)
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Chondrocytes
Gene expression
Matrix Metalloproteinase 13
Gene Expression
Messenger RNA
Retinoids
Mitogen-Activated Protein Kinases
Genes
Collagen Type X
Connective Tissue Growth Factor
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Polymerase chain reaction
Cartilage
p38 Mitogen-Activated Protein Kinases
Transcription
Tretinoin
Growth Plate
Immunoblotting
Reverse Transcription

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 journalArticle

Shimo, Tsuyoshi ; Koyama, Eiki ; Okui, Tatsuo ; Masui, Masanori ; Kunisada, Yuki ; Ibaragi, Soichiro ; Yoshioka, Norie ; Kurio, Naito ; Yoshida, Shoko ; Sasaki, Akira ; Iwamoto, Masahiro. / Retinoic Receptor Signaling Regulates Hypertrophic Chondrocyte-specific Gene Expression. In: In vivo (Athens, Greece). 2019 ; Vol. 33, No. 1. pp. 85-91.
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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.",
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AU - Kunisada, Yuki

AU - Ibaragi, Soichiro

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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.

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KW - connective tissue growth factor

KW - matrix metalloproteinase

KW - mitogen-activated protein kinase

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