CCN4 induces vascular cell adhesion molecule-1 expression in human synovial fibroblasts and promotes monocyte adhesion

Ju Fang Liu, Sheng Mou Hou, Chun Hao Tsai, Chun Yin Huang, Chin Jung Hsu, Chih Hsin Tang

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14 Citations (Scopus)


CCN4 is a cysteine-rich protein that belongs to the Cyr61, CTGF, Nov family of matricellular proteins. Here, we investigated the intracellular signaling pathways involved in CCN4-induced vascular cell adhesion molecule-1 expression in human osteoarthritis synovial fibroblasts. Stimulation of OASFs with CCN4 induced VCAM-1 expression. CCN4-induced VCAM-1 expression was attenuated by αvβ5 or α6β1 integrin antibody, Syk inhibitor, PKCδ inhibitor (rottlerin), JNK inhibitor (SP600125), and AP-1 inhibitors (curcumin and tanshinone). Stimulation of cells with CCN4 increased Syk, PKCδ, and JNK activation. Treatment of OASFs with CCN4 also increased c-Jun phosphorylation, AP-1-luciferase activity, and c-Jun binding to the AP-1 element in the VCAM-1 promoter. Moreover, up-regulation of VCAM-1 increased the adhesion of monocytes to OASF monolayers, and this adhesion was attenuated by transfection with a VCAM-1 siRNA. Our results suggest that CCN4 increases VCAM-1 expression in human OASFs via the Syk, PKCδ, JNK, c-Jun, and AP-1 signaling pathways. The CCN4-induced VCAM-1 expression promoted monocyte adhesion to human OASFs.

Original languageEnglish
Pages (from-to)966-975
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number5
Publication statusPublished - May 1 2013



  • CCN4
  • Integrin
  • OA
  • Syk
  • VCAM-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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