Yangonin treats inflammatory osteoporosis by inhibiting the secretion of inflammatory factors and RANKL expression

Objectives: As the main cause of osteoporosis, abnormal activity of osteoclasts could disrupt the balance between bone resorption and formation. Moreover, up-regulation of nuclear factor-kappa ligand (RANKL) expression by chronic inflammation-mediated inflammatory factors might contribute to the differentiation of osteoclast precursor cells. Therefore, an anti-inflammatory agent named yangonin was presented for inhibiting osteoclast and relieving inflammatory osteoporosis through down-regulating inflammatory factors.

Methods: We established a model of macrophage inflammation and then verified the anti-inflammatory effect of yangonin. The inhibitory effect of yangonin on osteoclasts was detected by tartrate-resistant Acid Phosphatase (TRAP) staining, Western blotting and quantitative Real-Time PCR (qRT-PCR). Finally, micro-CT, TRAP and hematoxylin-eosin (HE) staining were used to show the effect of yangonin on inflammatory osteoporosis in vivo.

Results: Our results suggested that yangonin was able to reduce the secretion of inflammatory factors, down-regulate osteoclast-related genes such as TRAP, RANKL, Cathepsin K (CTSK) and nuclear factor-activated T-cell 1 (NFATc1). Furthermore, it was demonstrated that yangonin could suppress the function of inflammatory cytokines in osteoclast differentiation and reporting, wherein NF-κB, Akt and downstream c-Fos/NFATc1 signaling pathways were involved. In an in vivo study, we implied that yangonin has a relieving effect on inflammatory osteoporosis.

Conclusion: Our research shows that yangonin down-regulates inflammatory factors and inhibits the bone-breaking effect of inflammation through NF-κB, Akt and downstream c-Fos/NFATc1 signaling pathways to achieve the purpose of treating inflammatory osteoporosis.