CTGF/Hcs24, hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and differentiation of chondrocytes

Takashi Nishida, Satoshi Kubota, Tomohiro Fukunaga, Seiji Kondo, Gen Yosimichi, Tohru Nakanishi, Teruko Takano-Yamamoto, Masaharu Takigawa

Research output: Contribution to journalArticle

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Abstract

Connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) plays important roles in the control of the proliferation and differentiation of chondrocytes in vitro. To clarify the mechanisms of regulation by CTGF/Hcs24 with respect to cartilage metabolism, we investigated the interaction between CTGF/Hcs24 and heparan sulfate proteoglycan perlecan. An immunofluorescence study showed that CTGF/Hcs24 was colocalized with heparan sulfate and perlecan in human chondrosarcoma-derived chondrocytic cell line HCS-2/8 in vitro. Northern blot analysis showed that perlecan, syndecan-1, -2, and -4 transcripts were detected in HCS-2/8 cells. Particularly, expression of the perlecan gene increased markedly in HCS-2/8 cells by recombinant CTGF/Hcs24 (rCTGF/Hcs24) treatment. We also found that CTGF/Hcs24 interacted with perlecan from HCS2/8 cells in vitro. Furthermore, CTGF/Hcs24-stimulated gene expression of the aggrecan gene, as well as DNA/proteoglycan synthesis, was diminished when HCS-2/8 cells were pretreated with heparinase, indicating that the effects of CTGF/Hcs24 on chondrocytes occurred through the interaction between CTGF/Hcs24 and heparan sulfate on the cells. An in vivo study using mouse growth plate revealed that CTGF/Hcs24 produced by hypertrophic chondrocytes was localized from the proliferative to the hypertrophic zone, whereas perlecan was predominantly localized in the prehyphertrophic zone. Consistent with such findings in vivo, the binding of 125I-rCTGF/Hcs24 to maturing chondrocytes was at higher levels than that to chondrocytes in hypertrophic stages. These findings suggest that CTGF/Hcs24 produced in the hypertrophic region may act on chondrocytes in the proliferative and maturative zone via some heparan sulfate proteoglycan, such as perlecan.

Original languageEnglish
Pages (from-to)265-275
Number of pages11
JournalJournal of Cellular Physiology
Volume196
Issue number2
DOIs
Publication statusPublished - Aug 1 2003

Fingerprint

Connective Tissue Growth Factor
Chondrocytes
Genes
Heparan Sulfate Proteoglycans
Heparitin Sulfate
perlecan
Syndecan-1
Heparin Lyase
Aggrecans
Syndecan-2
Cartilage
Proteoglycans
Gene Expression
Metabolism
Gene expression
Chondrosarcoma
Growth Plate

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

CTGF/Hcs24, hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and differentiation of chondrocytes. / Nishida, Takashi; Kubota, Satoshi; Fukunaga, Tomohiro; Kondo, Seiji; Yosimichi, Gen; Nakanishi, Tohru; Takano-Yamamoto, Teruko; Takigawa, Masaharu.

In: Journal of Cellular Physiology, Vol. 196, No. 2, 01.08.2003, p. 265-275.

Research output: Contribution to journalArticle

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abstract = "Connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) plays important roles in the control of the proliferation and differentiation of chondrocytes in vitro. To clarify the mechanisms of regulation by CTGF/Hcs24 with respect to cartilage metabolism, we investigated the interaction between CTGF/Hcs24 and heparan sulfate proteoglycan perlecan. An immunofluorescence study showed that CTGF/Hcs24 was colocalized with heparan sulfate and perlecan in human chondrosarcoma-derived chondrocytic cell line HCS-2/8 in vitro. Northern blot analysis showed that perlecan, syndecan-1, -2, and -4 transcripts were detected in HCS-2/8 cells. Particularly, expression of the perlecan gene increased markedly in HCS-2/8 cells by recombinant CTGF/Hcs24 (rCTGF/Hcs24) treatment. We also found that CTGF/Hcs24 interacted with perlecan from HCS2/8 cells in vitro. Furthermore, CTGF/Hcs24-stimulated gene expression of the aggrecan gene, as well as DNA/proteoglycan synthesis, was diminished when HCS-2/8 cells were pretreated with heparinase, indicating that the effects of CTGF/Hcs24 on chondrocytes occurred through the interaction between CTGF/Hcs24 and heparan sulfate on the cells. An in vivo study using mouse growth plate revealed that CTGF/Hcs24 produced by hypertrophic chondrocytes was localized from the proliferative to the hypertrophic zone, whereas perlecan was predominantly localized in the prehyphertrophic zone. Consistent with such findings in vivo, the binding of 125I-rCTGF/Hcs24 to maturing chondrocytes was at higher levels than that to chondrocytes in hypertrophic stages. These findings suggest that CTGF/Hcs24 produced in the hypertrophic region may act on chondrocytes in the proliferative and maturative zone via some heparan sulfate proteoglycan, such as perlecan.",
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