Inhibitory effect of vanillin on RANKL-induced osteoclast formation and function through activating mitochondrial-dependent apoptosis signaling pathway
Inhibitory effect of vanillin on RANKL-induced osteoclast formation and function through activating mitochondrial-dependent apoptosis signaling pathway
复制标题
香草醛通过激活线粒体依赖性凋亡信号通路对 RANKL 诱导的破骨细胞形成和功能产生抑制作用
DOI：
10.1016/j.lfs.2018.07.048
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发表时间：
2018-09-01
期刊：
影响因子：
6.1
通讯作者：
Dong, Shiwu
中科院分区：
文献类型：
--
作者：
Chen, Yueqi;Dou, Ce;Dong, Shiwu
骨质疏松、侵蚀性关节炎等骨基质稳态相关疾病是由破骨细胞介导的骨吸收和成骨细胞介导的骨形成失衡引起的。抑制破骨细胞与破骨细胞前体细胞的融合和分化是维持吸收和形成动态平衡的重要途径。近年来，一些天然产物被发现能抑制破骨细胞的形成，并具有潜在的治疗骨质疏松症的功能。香兰素此前被报道具有抗肿瘤和抗氧化活性，但其对骨骼健康的影响尚未阐明。在本研究中，我们发现香兰素对RANKL诱导的多核破骨细胞形成和骨吸收(浓度为0.25 mM-2.5 mM)有抑制作用。用TRAP和FAK染色观察香兰素对破骨细胞形态的影响，发现成熟破骨细胞数量减少，呈剂量依赖关系。香兰素可明显抑制RANKL诱导的破骨细胞分化过程中的骨吸收，促进早期细胞凋亡率。此外，香兰素通过诱导细胞色素c、裂解酪氨酸酶-3、Bax和APAF-1在mRNA和蛋白水平上的表达，激活线粒体依赖性的细胞凋亡。反之，则可抑制Bcl2的表达。因此，这些数据为香兰素可能成为治疗骨基质代谢性疾病的候选药物提供了线索。
Bone matrix homeostasis associated diseases such as osteoporosis and erosive arthritis were caused by the imbalance of osteoclast-mediated bone-resorption and osteoblast-mediated bone-formation. Suppressing the fusion and differentiation of osteoclast from osteoclast precursors are an essential way to maintain the dynamic balance of resorption and formation. Recently, some natural products were discovered to inhibit osteoclast formation and function for potential treatment of osteoporosis. Vanillin was previously reported to have anti-tumor and anti-oxidant activities; however, its effect on bone health has not been elucidated. In this study, we found that the inhibitory effect of vanillin on RANKL-induced multinucleated osteoclast formation and bone resorption (concentration of 0.25mM-2.5 mM). Morphologically, the number of mature osteoclasts was decreased after treating with vanillin in a dose-dependent manner, which was evaluated by TRAP staining and FAK staining. Vanillin could significantly inhibit bone resorption and promote the early apoptosis rate during RANKL-induced osteoclastogenesis. Furthermore, vanillin could activate the mitochondrial-dependent apoptosis via inducing the expression of cytochrome c, cleaved caspease-3, BAX and Apaf-1 both on mRNA and protein level. Otherwise, the expression of Bcl-2 was inhibited. Thereby, these data provide the clue that vanillin could be a candidate to treat bone matrix metabolic diseases.