Connective tissue growth factor promotes interleukin-1β-mediated synovial inflammation in knee osteoarthritis.

Connective tissue growth factor (CTGF), also known as CCN2, is a key proinflammatory mediator. In the present study, the involvement of the CTGF signaling pathway in human knee osteoarthritis (OA) fibroblast-like synoviocytes (FLSs) was investigated. FLSs were isolated from human OA synovium and incubated with CTGF in the absence or presence of interleukin‑1β (IL‑1β). The expression of relevant genes and proteins was analyzed by qPCR, western blotting and enzyme-linked immunosorbent assay (ELISA). Matrix metalloproteinase (MMP) activity and nuclear factor (NF)-κB activation were also evaluated. CTGF stimulation resulted in the significant production of IL-6, IL-8, C-C motif ligand 2 (CCL2), CCL20, MMP-1 and MMP-3 in FLSs in the presence, but not in the absence, of IL-1β. CTGF also enhanced the levels of phosphorylated extracellular signal-related kinase 1/2 (ERK1/2) and p38. In addition, CTGF at 25 ng/ml, in the presence of IL‑1β, significantly potentiated NF-κB activation. The results indicated that CTGF interacted with IL‑1β in FLSs to promote the inflammatory response in the synovium, leading to the initiation of the inflammatory cascade. These results support the proinflammatory role of CTGF in synovitis and joint destruction in OA.