Mechanism of osteoclast differentiation induced by sodium salicylate

点击翻译按钮获取中文摘要

Salicylates such as sodium salicylate and aspirin (acetylsalicylic acid) have been widely used for various inflammatory diseases including rheumatoid arthritis and periodontitis. However, the effects of salicylates on bone metabolism remain unclear. Here we investigated whether salicylates affect differentiation of mouse monocytic RAW264 cells into osteoclast-like cells. Either sodium salicylate or aspirin slightly induced differentiation of RAW264 cells into tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and enhanced osteoclast differentiation induced by a low concentration of receptor activator of nuclear factor-KB ligand (RANKL). Other nonsteroidal anti-inflammatory drugs (NSAIDs) without salicylic structure including ibuprofen, meloxicam and celecoxib did not affect osteoclast differentiation. Since it has been reported that mitogen-activated protein kinase (MAPK) signaling plays a crucial role in RANKL-induced osteoclast differentiation, the effects of salicylates on extracellular signal-regulated kinase (ERK) and p38 MAPK were examined. Phosphorylation of p38 was augmented whereas ERK phosphorylation was suppressed by aspirin or sodium salicylate. Furthermore, osteoclast differentiation induced by RANKL and salicylates was suppressed by SB203580, a specific inhibitor of p38 MAPK. These results were consistent with the previous report that RANKL-induced osteoclast differentiation was suppressed by inhibition of p38 whereas enhanced by ERK inhibition, suggesting that salicylates induce osteoclast differentiation via MAPK signaling in accordance with RANKL-induced osteoclast differentiation.