lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway

Molecular Medicine

Lin Shi¹  Qing-Jiang Pang¹  Xian-Jun Chen¹  Xiao Yu¹  Cheng-Hao Wang¹  Gong Feng²  Ze-Wen Shi²  Peng-Ze Rong²  Meng-Sheng Song² 

[1]Department of Orthopedics, HwaMei Hospital, University of Chinese Academy of Sciences, 315000, Ningbo, Zhejiang Province, China

[2]Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, No. 41 Xibei Street, 315000, Ningbo, Zhejiang Province, China

[3]Ningbo University School of Medicine, 315211, Ningbo, Zhejiang Province, China

关键词: LncRNA SNHG1;    miR-181c-5p;    SFRP1;    Wnt signal;    Bone remodeling;    Angiogenesis;   

DOI  :  10.1186/s10020-021-00392-2

来源: Springer

【 摘 要 】

BackgroundWe aimed to investigate the functions and underlying mechanism of lncRNA SNHG1 in bone differentiation and angiogenesis in the development of osteoporosis.MethodsThe differential gene or proteins expressions were measured by qPCR or western blot assays, respectively. The targeted relationships among molecular were confirmed through luciferase reporter, RIP and ChIP assays, respectively. Alkaline phosphatase (ALP), alizarin red S (ARS) and TRAP staining were performed to measure the osteoblast/osteoclast differentiation of BMSCs. The viability, migration and angiogenesis in BM-EPCs were validated by CCK-8, clone formation, transwell and tube formation assays, respectively. Western blot and immunofluorescence detected the cytosolic/nuclear localization of β-catenin. Ovariectomized (OVX) mice were established to confirm the findings in vitro.ResultsSNHG1 was enhanced and miR-181c-5p was decreased in serum and femoral tissue from OVX mice. SNHG1 directly inhibited miR-181c-5p to activate Wnt3a/β-catenin signaling by upregulating SFRP1. In addition, knockdown of SNHG1 promoted the osteogenic differentiation of BMSCs by increasing miR-181c-5p. In contrast, SNHG1 overexpression advanced the osteoclast differentiation of BMSCs and inhibited the angiogenesis of BM-EPCs, whereas these effects were all reversed by miR-181c-5p overexpression. In vivo experiments indicated that SNHG1 silencing alleviated osteoporosis through stimulating osteoblastogenesis and inhibiting osteoclastogenesis by modulating miR-181c-5p. Importantly, SNHG1 could be induced by SP1 in BMSCs.ConclusionsCollectively, SP1-induced SNHG1 modulated SFRP1/Wnt/β-catenin signaling pathway via sponging miR-181c-5p, thereby inhibiting osteoblast differentiation and angiogenesis while promoting osteoclast formation. Further, SNHG1 silence might provide a potential treatment for osteoporosis.Graphic abstract

【 授权许可】

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