Osteoclast differentiation induced by salicylates via MAPK signaling

• Published in: Journal of Osaka Dental University Vol. 43; no. 2; pp. 149 - 156
• Main Authors: Yakushiji, Kentaro, Sawai, Hirofumi, Inami, Kaoru, Katao, Yuko, Domae, Naochika
• Format: Journal Article
• Language: English
• Published: Osaka Odontological Society 2009
• Subjects: Aspirin; ERK; Osteoclast differentiation; p38 MAPK; RANKL; Salicylates
• ISSN: 0475-2058; 2189-6488
• DOI: 10.18905/jodu.43.2_149

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. We investigated whether salicylates affect differentiation of mouse monocytic RAW264 cells into osteoclast-like cells. Both sodium salicylate and 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-κB 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, we examined the effects of salicylates on extracellular signal-regulated kinase (ERK) and p38 MAPK. Although phosphorylation of p38 was augmented by both aspirin and sodium salicylate, ERK phosphorylation was suppressed. 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 which found that although RANKL-induced osteoclast differentiation was suppressed by inhibition of p38, it was enhanced by ERK inhibition. This suggests that salicylates induce osteoclast differentiation via MAPK signaling.