CCN2 (Connective Tissue Growth Factor) is essential for extracellular matrix production and integrin signaling in chondrocytes

Takashi Nishida, Harumi Kawaki, Ruth M. Baxter, R. Andrea DeYoung, Masaharu Takigawa, Karen M. Lyons

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

The matricellular protein CCN2 (Connective Tissue Growth Factor; CTGF) is an essential mediator of ECM composition, as revealed through analysis of Ccn2 deficient mice. These die at birth due to complications arising from impaired endochondral ossification. However, the mechanism(s) by which CCN2 mediates its effects in cartilage are unclear. We investigated these mechanisms using Ccn2-/- chondrocytes. Expression of type II collagen and aggrecan were decreased in Ccn2-/- chondrocytes, confirming a defect in ECM production. Ccn2-/- chondrocytes also exhibited impaired DNA synthesis and reduced adhesion to fibronectin. This latter defect is associated with decreased expression of α5 integrin. Moreover, CCN2 can bind to integrin α5β1 in chondrocytes and can stimulate increased expression of integrin α5. Consistent with an essential role for CCN2 as a ligand for integrins, immunofluorescence and Western blot analysis revealed that levels of focal adhesion kinase (FAK) and extracellular signalregulated kinase (ERK)1/2 phosphorylation were reduced in Ccn2-/- chondrocytes. These findings argue that CCN2 exerts major effects in chondrocytes through its ability to (1) regulate ECM production and integrin α5 expression, (2) engage integrins and (3) activate integrin-mediated signaling pathways.

Original languageEnglish
Pages (from-to)45-58
Number of pages14
JournalJournal of Cell Communication and Signaling
Volume1
Issue number1
DOIs
Publication statusPublished - 2007

Keywords

  • Chondrocyte
  • Connective tissue growth factor/CCN2
  • Extracellular signal-regulated kinase (ERK)1/2
  • Fibronectin
  • Focal adhesion kinase (FAK)
  • Integrinα5

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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