Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity, which is closely associated with inflammation. Benzydamine (BA) has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of pro-inflammatory cytokines or prostaglandins. However, its role in osteoclast differentiation and function remains unknown. Here, we explored the role of BA in regulating osteoclast differentiation and elucidated the underlying mechanism. BA inhibited osteoclast differentiation and strongly suppressed interleukin-1β (IL-1β) production. BA inhibited osteoclast formation and bone resorption when added to bone marrow-derived macrophages and differentiated osteoclasts, and the inhibitory effect was reversed by IL-1β treatment. The reporter assay and the inhibitor study of IL-1β transcription suggested that BA inhibited nuclear factor-κB and activator protein-1 by regulating IκB kinase, extracellular signal regulated kinase and P38, resulting in the down-regulation of IL-1β expression. BA also promoted osteoblast differentiation. Furthermore, BA protected lipopolysaccharide- and ovariectomy-induced bone loss in mice, suggesting therapeutic potential against inflammation-induced bone diseases and postmenopausal osteoporosis.

骨质疏松症和牙周炎等骨病是由过度的破骨细胞活性引起的，而破骨细胞活性与炎症密切相关。苯达明（BA）已被用作抑制促炎细胞因子或前列腺素产生的细胞因子抑制或非甾体抗炎药。然而，其在破骨细胞分化和功能中的作用仍然未知。在这里，我们探讨了BA在调节破骨细胞分化中的作用，并阐明了其潜在机制。BA抑制破骨细胞分化和强烈抑制白介素-1 β（IL-1 β）的生产。当添加到骨髓来源的巨噬细胞和分化的破骨细胞中时，BA抑制破骨细胞的形成和骨吸收，IL-1逆转了其抑制作用β治疗。报道分子分析和IL-1抑制剂研究β转录表明BA抑制核因子κ通过调节I B和激活蛋白-1 κ乙激酶，胞外信号调节激酶和P38，从而导致IL-的下调1个β表达。BA还促进成骨细胞分化。此外，BA保护小鼠的脂多糖和卵巢切除术引起的骨质流失，表明其对炎症引起的骨病和绝经后骨质疏松症具有治疗潜力。