Yang Jing-Jin, Peng Wei-Xia, Zhang Mei-Biao
Department of Endocrinology, The First People's Hospital of Huaihua, HuaiHua, 418000, Hunan Province, PR China.
Department of Endocrinology, Yiyang Central Hospital, YiYang, 413000, Hunan Province, PR China.
Exp Cell Res. 2022 Jun 1;415(1):113119. doi: 10.1016/j.yexcr.2022.113119. Epub 2022 Mar 24.
Osteoporosis is a prevalent degenerative disease that is characterized by decreased bone density and strength, resulting in gradually increasing bone fragility. Osteoporosis is caused by an imbalance between osteoblastic bone formation and osteoclastic bone resorption. Recently, increasing evidence has suggested that long non-coding RNAs (lncRNAs) participate in the occurrence and development of osteoporosis. Herein, we explored the role of lncRNA KCNQ1OT1 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). QPCR results indicated that KCNQ1OT1 and RICTOR were down-regulated, while miR-205-5p was up-regulated in the osteoporotic patients, as compared with non-osteoporotic controls. During the osteogenic differentiation of BMSCs, the expression of KCNQ1OT1 and RICTOR was upregulated, whereas miR-205-5p was downregulated. The interaction among KCNQ1OT1, miR-205-5p and RICTOR was validated by dual luciferase reporter system. KCNQ1OT1 promoted RICTOR expression via inhibiting miR-205-5p, therefore promoting osteogenesis as demonstrated by ALP assay, alizarin red staining and the increased expression of osteogenic markers (OPN, RUNX2 and OCN). Furthermore, KCNQ1OT1 overexpression or miR-205-5p inhibition could promote ALP activity and mineralization of BMSCs, while overexpressed miR-205-5p could reverse the effects of overexpressed KCNQ1OT1, and knockdown of RICTOR could reverse the effects of miR-205-5p inhibition. In conclusion, our study illustrated that KCNQ1OT1 might inhibit miR-205-5p in BMSCs, thus upregulating the expression of RICTOR and promoting osteogenic differentiation.
骨质疏松症是一种常见的退行性疾病，其特征是骨密度和强度降低，导致骨脆性逐渐增加。骨质疏松症是由成骨细胞骨形成与破骨细胞骨吸收之间的失衡引起的。最近，越来越多的证据表明长链非编码RNA（lncRNAs）参与了骨质疏松症的发生和发展。在此，我们探讨了lncRNA KCNQ1OT1在骨髓间充质干细胞（BMSCs）成骨分化中的作用。定量聚合酶链反应（QPCR）结果表明，与非骨质疏松症对照组相比，骨质疏松症患者中KCNQ1OT1和RICTOR表达下调，而miR-205-5p表达上调。在BMSCs成骨分化过程中，KCNQ1OT1和RICTOR的表达上调，而miR-205-5p的表达下调。双荧光素酶报告系统验证了KCNQ1OT1、miR-205-5p和RICTOR之间的相互作用。KCNQ1OT1通过抑制miR-205-5p促进RICTOR表达，因此通过碱性磷酸酶（ALP）测定、茜素红染色和成骨标志物（骨桥蛋白、RUNX2和骨钙素）表达增加证明促进了成骨作用。此外，KCNQ1OT1过表达或miR-205-5p抑制可促进BMSCs的ALP活性和矿化，而过表达的miR-205-5p可逆转KCNQ1OT1过表达的作用，敲低RICTOR可逆转miR-205-5p抑制的作用。总之，我们的研究表明KCNQ1OT1可能在BMSCs中抑制miR-205-5p，从而上调RICTOR的表达并促进成骨分化。
