Long non-coding RNA SNHG5 promotes the osteogenic differentiation of bone marrow mesenchymal stem cells via the miR-212-3p/GDF5/SMAD pathway

BACKGROUND: The treatment of bone loss has posed a challenge to clinicians for decades. Thus, it is of great significance to identify more effective methods for bone regeneration. However, the role and mechanisms of long non-coding RNA small nucleolar RNA host gene 5 (SNHG5) during osteogenic differentiation remain unclear. METHODS: We investigated the function of SNHG5, Yin Yang 1 (YY1), miR-212-3p and growth differentiation factor 5 (GDF5) in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro and in vivo. Molecular mechanisms were clarified by chromatin immunoprecipitation assay and dual luciferase reporter assay. RESULTS: We found SNHG5 expression was upregulated during osteogenesis of hBMSCs. Knockdown of SNHG5 in hBMSCs inhibited osteogenic differentiation while overexpression of SNHG5 promoted osteogenesis. Moreover, YY1 transcription factor directly bound to the promoter region of SNHG5 and regulated SNHG5 expression to promote osteogenesis. Dual luciferase reporter assay confirmed that SNHG5 acted as a miR-212-3p sponge and miR-212-3p directly targeted GDF5 and further activated Smad1/5/8 phosphorylation. miR-212-3p inhibited osteogenic differentiation, while GDF5 promoted osteogenic differentiation of hBMSCs. In addition, calvarial defect experiments showed knockdown of SNHG5 and GDF5 inhibited new bone formation in vivo. CONCLUSION: Our results demonstrated that the novel pathway YY1/SNHG5/miR-212-3p/GDF5/Smad regulates osteogenic differentiation of hBMSCs and may serve as a potential target for the treatment of bone loss. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-02781-8.