Wang Haitao, Wei Peng, Zhang Yi, Li Yuebai, Yin Li
Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Cell Dev Biol. 2021 Jun 28;9:697858. doi: 10.3389/fcell.2021.697858. eCollection 2021.
Long noncoding RNA (lncRNA) is a noncoding RNA with a length of more than 200 bases. It plays an important role in the occurrence and development of diseases. Research on lncRNAs has received increasing attention. Bone is an important organ of the human body. As the population ages, the incidence of osteoporosis gradually increases. The mechanism of action of lncRNAs in the development of osteoporosis is unclear. The imbalance between osteogenic and adipogenic differentiation in bone marrow mesenchymal stem cells (hBMSCs) and the coupling process of osteogenesis and angiogenesis plays an important role in the development of osteoporosis. Therefore, this study focused on the mechanism by which lncRNAs regulate the osteogenic differentiation of bone marrow mesenchymal stem cells and the mechanism of action of lncRNAs in bone metabolism. The expression of lncRNAs in the osteogenic differentiation of hBMSCs was detected by lncRNA microarray. Real-time quantitative PCR was used to detect the expression changes of lncRNA and osteogenic genes during hBMSC osteogenic and adipogenic differentiation. The ceRNA mechanisms were detected by RIP and luciferase reporter gene assays. The effect of lncRNAs on the osteogenesis-angiogenesis coupling process was detected by Transwell assays. TCONS_00023297 increased expression during osteogenic differentiation; TCONS_00023297 overexpression promoted osteogenic differentiation of hBMSCs; BMP2 regulated TCONS_00023297 expression in a concentration- and time-dependent manner; TCONS_00023297 regulated miR-608 via a ceRNA mechanism; TCONS_00023297 inhibited hBMSC adipogenic differentiation; and TCONS_00023297 promoted VEGF secretion by hBMSCs. TCONS_00023297 regulates osteogenic differentiation, adipogenic differentiation, and osteogenic-angiogenic coupling of hBMSCs via the TCONS_00023297/miR-608/RUNX2/SHH signaling axis.
长链非编码RNA（lncRNA）是一种长度超过200个碱基的非编码RNA。它在疾病的发生和发展中起重要作用。对lncRNAs的研究受到越来越多的关注。骨骼是人体的重要器官。随着人口老龄化，骨质疏松症的发病率逐渐上升。lncRNAs在骨质疏松症发展中的作用机制尚不清楚。骨髓间充质干细胞（hBMSCs）中成骨分化与成脂分化之间的失衡以及成骨与血管生成的偶联过程在骨质疏松症的发展中起重要作用。因此，本研究聚焦于lncRNAs调节骨髓间充质干细胞成骨分化的机制以及lncRNAs在骨代谢中的作用机制。通过lncRNA芯片检测lncRNAs在hBMSCs成骨分化中的表达。采用实时定量PCR检测hBMSCs成骨和成脂分化过程中lncRNA和成骨基因的表达变化。通过RIP和荧光素酶报告基因检测ceRNA机制。通过Transwell检测lncRNAs对成骨-血管生成偶联过程的影响。TCONS_00023297在成骨分化过程中表达增加；TCONS_00023297过表达促进hBMSCs的成骨分化；BMP2以浓度和时间依赖性方式调节TCONS_00023297的表达；TCONS_00023297通过ceRNA机制调节miR-608；TCONS_00023297抑制hBMSCs的成脂分化；TCONS_00023297促进hBMSCs分泌VEGF。TCONS_00023297通过TCONS_00023297/miR-608/RUNX2/SHH信号轴调节hBMSCs的成骨分化、成脂分化和成骨-血管生成偶联。
