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
Ya-Ge Tian, Li-Ling Liu, Ming-Zhu Qi, Jing-Hang Yang, Pan-Pan Zhu, Na Lin, Xiao-Hui Su, Xiang-Ying KongAbstract
Objective:
The objective of this study was to investigate the effect of glycosides of
Materials and Methods:
The effects of GTW on bone destruction were assessed through hematoxylin and eosin analyses and tartrate-resistant acid phosphatase (TRAP) staining.
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.