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Mechanism of osteoclast differentiation induced by sodium salicylate

水杨酸钠诱导破骨细胞分化的机制

基本信息

批准号：
18592078
负责人：
SAWAI Hirofumi
金额：
$ 2.4万
依托单位：
Osaka Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592078/
关键词：
osteoclast RANKL ERK p38 MAPK sodium salicylate aspirin NSAID p38 MAPK p38

项目摘要

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.

水杨酸盐如水杨酸钠和阿司匹林(乙酰水杨酸)已被广泛用于治疗各种炎症性疾病，包括类风湿性关节炎和牙周炎。然而，水杨酸盐对骨代谢的影响仍不清楚。在这里，我们研究了水杨酸盐是否影响小鼠单核细胞RAW264细胞向破骨细胞样细胞的分化。水杨酸钠或阿司匹林均能轻微诱导RAW264细胞分化为抗酒石酸酸性磷酸酶(TRAP)阳性破骨细胞，并能增强低浓度核因子受体激活剂(RANKL)诱导的破骨细胞分化。布洛芬、美洛昔康和塞来昔布等不含水杨酸结构的非甾体抗炎药不影响破骨细胞的分化。鉴于有报道称丝裂原活化蛋白激酶(MAPK)信号在RANKL诱导破骨细胞分化中起着关键作用，因此我们研究了水杨酸盐对细胞外信号调节激酶(ERK)和p38MAPK的影响。阿司匹林或水杨酸钠可促进p38的磷酸化，而抑制ERK的磷酸化。此外，p38 MAPK的特异性抑制剂SB203580可抑制RANKL和水杨酸盐诱导的破骨细胞分化。这些结果与先前报道的RANKL诱导的破骨细胞分化被p38抑制而ERK抑制相一致，提示水杨酸盐通过MAPK信号途径诱导破骨细胞分化与RANKL诱导的破骨细胞分化一致。