Piperine alleviates osteoclast formation through the p38/c-Fos/NFATc1 signaling axis
Piperine alleviates osteoclast formation through the p38/c-Fos/NFATc1 signaling axis
复制标题
DOI：
10.1002/biof.1241
复制
发表时间：
2015-11-01
期刊：
影响因子：
6
通讯作者：
Coetzee, Magdalena
中科院分区：
文献类型：
--
作者：
Deepak, Vishwa;Kruger, Marlena C.;Coetzee, Magdalena
骨折增加是骨质疏松症和乳腺癌骨转移等骨丢失相关疾病患者的健康风险因素之一。破骨细胞的过度活性导致骨重建的解偶联，有利于骨丢失而不是骨形成。核因子-配体受体激活因子（RANKL）触发分化途径，导致多核破骨细胞形成。RANKL或其下游信号通路参与破骨细胞形成的调节在抗吸收剂的开发中具有重要意义。本研究以胡椒中的生物碱胡椒碱为研究对象，探讨了胡椒碱对胡椒醛合成的影响。对破骨细胞形成的影响。在RANKL和乳腺癌细胞诱导的鼠RAW264.7巨噬细胞和人CD 14+单核细胞中，马槟榔碱抑制抗酒石酸酸性磷酸酶阳性多核破骨细胞的形成。马槟榔碱减弱了p38-丝裂原活化蛋白激酶途径的活化，而细胞外信号调节激酶、c-Jun N-末端激酶或RANKL下游的NF-途径不受影响。同时，胡椒碱显著抑制破骨细胞生成中的关键转录因子c-Fos和活化T细胞核因子胞质1（NFATc 1）的表达。此外，胡椒碱破坏肌动蛋白环结构和骨吸收，破骨细胞的特征标志。总的来说，这些结果表明胡椒碱通过抑制p38/NFATc 1/c-Fos信号轴来抑制破骨细胞分化。(c)2015生物因子，41（6）：403-413，2015
Increased bone fracture is one of the health risk factors in patients with bone loss related disorders such as osteoporosis and breast cancer metastasis to bone. Over activity of osteoclasts leads to uncoupling of bone remodeling favoring bone loss over bone formation. Receptor activator of nuclear factor- ligand (RANKL) triggers the differentiation pathway leading to multinucleated osteoclast formation. Modulation of RANKL or its downstream signaling pathways involved in osteoclast formation is of significant interest in the development of anti-resorptive agents. In this study, the effects of piperine, an alkaloid present in Piper nigrum L. on osteoclast formation was investigated. Piperine inhibited tartrate-resistant acid phosphatase-positive multinucleated osteoclast formation in murine RAW264.7 macrophages and human CD14+ monocytes induced by RANKL and breast cancer cells. Piperine attenuated the p38-mitogen activated protein kinase pathway activation, while the extracellular-signal-regulated kinase, c-Jun N-terminal kinase, or NF- pathways downstream of RANKL remained unaffected. Concomitantly, expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), the key transcription factors involved in osteoclastogenesis were remarkably inhibited by piperine. Furthermore, piperine disrupted the actin ring structure and bone resorption, a characteristic hallmark of osteoclasts. Collectively, these results suggested that piperine inhibited osteoclast differentiation by suppressing the p38/NFATc1/c-Fos signaling axis. (c) 2015 BioFactors, 41(6):403-413, 2015