LncRNA JHDM1D-AS1 promotes osteogenic differentiation of periodontal ligament cells by targeting miR-532-5p to activate IGF1R signaling

Objective: The aim of this study was to explore the mechanism underlying periodontal ligament cells (PDLCs) osteogenic differentiation.

Background: Periodontitis causes damage to tooth-supporting apparatus and eventually leads to tooth loss. PDLCs hold great promise in periodontal regeneration due to their osteogenic features.

Methods: The expression of osteogenic markers, lncRNA JHDM1D-AS1, miR-532-5p and IGF1R was examined. For osteogenic differentiation, primary human PDLCs (hPDLCs) were cultured in an osteogenic medium, and it was assessed by ALP activity and Alizarin Red staining. The interaction between JHDM1D-AS1, miR-532-5p and IGF1R was analyzed via dual luciferase, RIP and RNA pull-down assays.

Results: JHDM1D-AS1 was up-regulated during osteogenic differentiation and its silencing inhibited hPDLC osteogenic differentiation. JHDM1D-AS1 worked as a miR-532-5p sponge in hPDLCs. miR-532-5p directly targeted IGF1R to suppress its expression, and miR-532-5p knockdown facilitated osteogenic differentiation of hPDLCs. Overexpression of IGF1R promoted osteogenic differentiation of hPDLCs via activating Notch/HES1 signaling in hPDLCs.

Conclusion: JHDM1D-AS1 promotes osteogenic differentiation of hPDLCs via sponging miR-532-5p to facilitate IGF1R expression and activate Notch/HES1 signaling.