Glycosides of Tripterygium wilfordii Hook. F Inhibits Bone Loss in Rheumatoid Arthritis by Downregulating Interleukin-8/C-X-C Motif Chemokine Receptor 2 Signaling Pathway

Objective: The objective of this study was to investigate the effect of glycosides of Tripterygium wilfordii Hook. F (GTW) on bone erosion in collagen-induced arthritis (CIA) rats and osteoclastogenesis. Materials and Methods: The effects of GTW on bone destruction were assessed through hematoxylin and eosin analyses and tartrate-resistant acid phosphatase (TRAP) staining. In vitro , TRAP staining, F-actin, and quantitative polymerase chain reaction assays were used to evaluate the inhibitory effects of GTW on osteoclast differentiation. In addition, Western blot, immunohistochemistry, and immunofluorescence staining techniques were employed to explore the mechanisms of GTW by determining the expression of interleukin-8 (IL-8), C-X-C motif chemokine receptor 2 (CXCR2), nuclear factor of activated T cells 1 (NFATc1), and p65. Results: GTW slowed the onset of arthritis and reduced arthritis scores. Our mechanistic studies demonstrated that GTW reduced the number of osteoclasts in rats with CIA and significantly suppressed receptor activator of nuclear factor kappa-B ligand-induced osteoclast differentiation, as evidenced by a decrease in TRAP-positive cells, alterations in F-actin rings, and modulation of osteoclast-specific gene expression. The inhibition of IL-8, CXCR2, NFATc1, and p65 activation by GTW was observed in both CIA rats and osteoclasts. Conversely, the introduction of IL-8 into the osteoclast culture system mitigated the effects of GTW on osteoclast differentiation. Conclusions: Our findings suggest that GTW suppressed osteoclastogenesis and bone loss by inhibiting the IL-8/CXCR2 signaling pathway. These results offer valuable insights into the potential therapeutic role of GTW in rheumatoid arthritis and lay the groundwork for future clinical applications.