Arthritogenic action of gliostatin in rheumatoid arthritis and its molecular mechanism.

点击翻译按钮获取中文摘要

Neovascularization, proliferation of synovial cells, and mononuclear cell influx and activation are characteristic events observed in synovial joints in the pathohistology of rheumatoid arthritis (RA). The purposes of this study are to examine how gliostatin/platelet derived-endothelial cell growth factor (GLS/PD-ECGF) is involved in the molecular mechanism of cartilage degradation and whether measurement of serum GLS can be used to evaluate symptomatic improvements after surgery (arthroplasty or synovectomy) in RA.Intraarticular injection of rHuGLS in rabbit knee joints resulted in development of diffuse synovitis, chondrocytes destruction, and pannus formation resembling rheumatoid arthritis. A chondrosarcoma cell line (OUMS-27) was cultured and treated with interleukin-lβ (IL-1β). IL-1β induced the expression of matrix metalloproteinase (MMP)-1, MMP-13, and GLS. Patients with RA undergoing arthroplasty demonstrated a decrease in serum GLS levels after operations.These findings suggest that GLS is a plausible pathogenic factor causing the extensive joint destruction in RA mediated via MMPs and that human GLS can cause RA-like synovitis via a mechanism other than its thymidine phosphorylase activity and that the serum GLS level is a useful indicator for evaluation of synovitis and the systemic efficacy of surgical treatment.