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

在类风湿关节炎(RA)的病理组织学中，滑膜细胞的新生血管、增殖以及单核细胞的涌入和激活是滑膜关节的特征事件。本研究的目的是探讨胶质抑制素/血小板衍生内皮细胞生长因子(GLS/PD-ECGF)如何参与RA软骨退化的分子机制，以及血清GLS的测定是否可用于评估RA手术(关节成形术或滑膜切除术)后症状的改善。兔膝关节内注射rHuGLS可导致弥漫性滑膜炎、软骨细胞破坏和类风湿性关节炎的血管疙瘩形成。培养软骨肉瘤细胞系(OUMS-27)，用白细胞介素1β(IL-1β)干预。IL-1β可诱导MMP1、MMP13和GLS的表达。关节置换术后RA患者血清GLS水平下降，提示GLS是MMPs介导的RA关节广泛破坏的可能致病因素，人类GLS可通过胸苷磷酸化酶以外的其他机制引起类风湿性滑膜炎，血清GLS水平可作为评价滑膜炎和手术治疗系统疗效的有用指标。

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.