Department of Microbiology, Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China.
School of Biomedical Sciences, University of Western Australia, Perth, Western Australia, Australia.
J Cell Biochem. 2018 Jun;119(6):4826-4835. doi: 10.1002/jcb.26682. Epub 2018 Mar 9.
Osteoclasts are highly differentiated multinucleated giant cells that play fundamental roles in bone resorption and in the pathogenesis of osteolytic conditions, such as osteoporosis and cancer-induced bone loss. Achyranthes bidentata polysaccharide (ABP) is a hydrophilic compound with anti-oxidation and anti-aging characteristics. The impact of ABP on RANKL-induced osteoclast formation and bone resorption has not been assessed, hence, in this study we investigated the effect of ABP on osteoclast formation and resorption in murine bone marrow derived osteoclasts. We found that ABP was able to suppress RANKL-induced osteoclast differentiation and bone resorption activity at concentrations above 6.5 µM, while demonstrating no cytotoxicity at concentrations up to 10 µM. The actions of ABP were mediated through inhibition of RANKL-induced c-Fos and NFATc1 gene and protein expression. Furthermore, we found that ABP suppressed NFATc1 transcriptional activity, and the phosphorylation of MAPK pathways induced by RANKL. Collectively, ABP attenuates RANKL-mediated osteoclast activity and signaling, and might serve as a potential therapeutic candidate for preventing bone loss related diseases.
破骨细胞是高度分化的多核巨细胞，在骨吸收和溶骨性疾病的发病机制中起着重要作用，如骨质疏松症和癌症引起的骨丢失。牛膝多糖（ABP）是一种具有抗氧化和抗衰老特性的亲水性化合物。ABP 对 RANKL 诱导的破骨细胞形成和骨吸收的影响尚未评估，因此，在这项研究中，我们研究了 ABP 对鼠骨髓来源破骨细胞形成和吸收的影响。我们发现，ABP 能够抑制浓度高于 6.5μM 的 RANKL 诱导的破骨细胞分化和骨吸收活性，而在高达 10μM 的浓度下没有细胞毒性。ABP 的作用是通过抑制 RANKL 诱导的 c-Fos 和 NFATc1 基因和蛋白表达来介导的。此外，我们发现 ABP 抑制了 RANKL 诱导的 NFATc1 转录活性和 MAPK 途径的磷酸化。总之，ABP 可减弱 RANKL 介导的破骨细胞活性和信号转导，可能成为预防与骨丢失相关疾病的潜在治疗候选药物。
