Tong Xiang, Gu Peng-cheng, Xu San-zhong, Lin Xiang-jin
a Department of Orthopedic Surgery, The 1st Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , China.
Biosci Biotechnol Biochem. 2015;79(5):732-7. doi: 10.1080/09168451.2014.998617. Epub 2015 Feb 9.
Osteoporosis is a common disease characterized by low bone mineral density (BMD) and low trauma fractures, mainly resulting from exceeding bone resorption by osteoclasts over bone formation by osteoblasts. Circulating monocytes are directly involved in osteoclastogenesis, and lncRNAs are believed to be involved in the osteoblast differentiation. However, no study has been conducted to identify the roles of lncRNA in circulating monocytes associated with human osteoporosis. In this study, we found significant upregulation of DANCR in the blood mononuclear cells (MNCs) from low-BMD patients with the qRT-PCR analyses. We further found that DANCR promoted the expression of IL6 and TNF-α at both mRNA level and protein level in MNCs. After deletion of DANCR with siRNAs, the levels of IL6 and TNF-α are decreased in the MNCs from low-BMD postmenopausal women. Moreover, DANCR level was correlated with IL6 and TNF-α in postmenopausal women with low BMD. Furthermore, we found that DANCR-induced IL6 and TNF-α in MNCs had bone-resorbing activity. These results indicate that DANCR is involved in the pathology of osteoporosis and may be as a biomarker for postmenopausal osteoporosis.
骨质疏松症是一种常见疾病，其特征为骨矿物质密度（BMD）低和低创伤性骨折，主要是由于破骨细胞的骨吸收超过成骨细胞的骨形成所致。循环单核细胞直接参与破骨细胞生成，并且长链非编码RNA（lncRNAs）被认为参与成骨细胞分化。然而，尚未开展研究来确定lncRNA在与人类骨质疏松症相关的循环单核细胞中的作用。在本研究中，通过qRT-PCR分析，我们发现低骨密度患者血液单核细胞（MNCs）中DANCR显著上调。我们进一步发现，DANCR在mRNA水平和蛋白质水平上均促进MNCs中IL6和TNF-α的表达。在用小干扰RNA（siRNAs）删除DANCR后，低骨密度绝经后女性的MNCs中IL6和TNF-α水平降低。此外，在低骨密度绝经后女性中，DANCR水平与IL6和TNF-α相关。此外，我们发现DANCR在MNCs中诱导的IL6和TNF-α具有骨吸收活性。这些结果表明，DANCR参与骨质疏松症的病理过程，可能作为绝经后骨质疏松症的生物标志物。
