Abstract
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
Highlights
We aimed to investigate the functions and underlying mechanism of Long non-coding RNAs (lncRNAs) small nucleolar RNA host gene 1 (SNHG1) in bone differen‐ tiation and angiogenesis in the development of osteoporosis
The protein levels of Alkaline phosphatase (ALP), Osteoc‐ alcin (OCN), Runt domain transcription factor 2 (RUNX2) and vascular endothelial growth factor (VEGF) decreased significantly in femoral tissue of OVX group compared with sham group, while the levels of NFATc1, Receptor activator of nuclear factor-κB ligand (RANKL) and Cathepsin K (CTSK) increased significantly (Fig. 1C and B)
Long non-coding RNAs (LncRNA) SNHG1 could bind to miR‐181c‐5p to repress its expression Generally, lncRNAs were reported to function as the molecular sponge of miRNA
Summary
We aimed to investigate the functions and underlying mechanism of lncRNA SNHG1 in bone differen‐ tiation and angiogenesis in the development of osteoporosis. Bone is a highly vascularized form of connective tissue and angiogenesis is required for bone formation (Kanczler and Oreffo 2008). It have proposed the concept of bone-vascular coupling, explaining that the angiogenesis of bone tissue is closely related to bone formation, bone remodeling and bone repair (Guo et al 2021; Ma et al 2021). The current treatments for osteoporosis are limited and usually combined with complications. It is urgent to explore the pathological mechanism of osteoporosis and find new effective treatment strategies
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