CCN1 induces oncostatin M production in osteoblasts via integrin-dependent signal pathways

• Published in: PloS one 2014-09, Vol.9 (9), p.e106632-e106632
• Main Authors: Chen, Cheng-Yu, Su, Chen-Ming, Huang, Yuan-Li, Tsai, Chun-Hao, Fuh, Lih-Jyh, Tang, Chih-Hsin
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Apoptosis; Arthritis; Biocompatibility; Biology and Life Sciences; Biotechnology; Blotting, Western; Bone surgery; Cell adhesion & migration; Cell culture; Cell Line; Chromatin Immunoprecipitation; CYR61 protein; Cysteine; Cysteine-Rich Protein 61 - pharmacology; Cytokines; Enzyme-Linked Immunosorbent Assay; Extracellular matrix; Focal adhesion kinase; Focal Adhesion Protein-Tyrosine Kinases - antagonists & inhibitors; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Gene amplification; Humans; Inflammation; Inflammatory response; Integrins; Integrins - metabolism; Kinases; Luciferase; Medicine and Health Sciences; Monoclonal antibodies; Motility; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB protein; Oncostatin M; Oncostatin M - genetics; Oncostatin M - metabolism; Osteoarthritis; Osteoblasts; Osteoblasts - drug effects; Osteoblasts - metabolism; Pathogenesis; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Polyclonal antibodies; Proteins; Real-Time Polymerase Chain Reaction; Rheumatoid arthritis; Science; Signal transduction; Signal Transduction - drug effects; Src protein; Studies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106632

Inflammatory response and articular destruction are common symptoms of osteoarthritis. Cysteine-rich 61 (CCN1 or Cyr61), a secreted protein from the CCN family, is associated with the extracellular matrix involved in many cellular activities like growth and differentiation. Yet the mechanism of CCN1 interacting with arthritic inflammatory response is unclear. This study finds CCN1 increasing expression of oncostatin m (OSM) in human osteoblastic cells. Pretreatment of αvβ3 monoclonal antibody and inhibitors of focal adhesion kinase (FAK), c-Src, phosphatidylinositol 3-kinase (PI3K), and NF-κB inhibited CCN1-induced OSM expression in osteoblastic cells. Stimulation of cells with CCN1 increased phosphorylation of FAK, c-Src, PI3K, and NF-κB via αvβ3 receptor; CCN1 treatment of osteoblasts increased NF-κB-luciferase activity and p65 binding to NF-κB element on OSM promoter. Results indicate CCN1 heightening OSM expression via αvβ3 receptor, FAK, c-Src, PI3K, and NF-κB signal pathway in osteoblastic cells, suggesting CCN1 as a novel target in arthritis treatment.