The Study of Mechanisms of Protective Effect of Rgl against Arthritis by Inhibiting Osteodast Differentiation and Maturation in CIA Mice

摘要

Ginsenoside Rgl is a natural product extracted from Panax ginseng C.A. Although Rgl protects tissue structure and functions by inhibiting local inflammatory reaction, the mechanism remains poorly understood. In vitro, Rgl dose-dependently inhibited TRAP activity in receptor activator of nuclear factor-KB ligand- (RANKL-) induced osteodasts and decreased the number of osteoclasts and osteoclast resorption area. Rgl also significantly inhibited the RANK signaling pathway, including suppressing the expression of Trap, cathepsin K, matrix metalloproteinase 9 (MMP9), and calcitonin receptor (CTR). In vivo, Rgl dramatically decreased arthritis scores in CIA mice and effectively controlled symptoms of inflammatory arthritis. Pathologic analysis demonstrated that Rgl significantly attenuated pathological changes in CIA mice. Pronounced reduction in synovial hyperplasia and inflammatory cell invasion were observed in CIA mice after Rgl therapy. Alcian blue staining results illustrated that mice treated with Rgl had significantly reduced destruction in the articular cartilage. TRAP and cathepsin K staining results demonstrated a significant reduction of numbers of OCs in the articular cartilage in proximal interphalangeal joints and ankle joints in Rgl-treated mice. In summary, this study revealed that Rgl reduced the inflammatory destruction of periarticular bone by inhibiting differentiation and maturation of osteoclasts in CIA mice.