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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. [ABSTRACT FROM AUTHOR]

Abstract Background MicroRNAs (miRNAs) are critical regulators in osteogenesis and cartilage formation. This study was designed to investigate whether miR-532-5p plays a role in the regulation of osteoporosis. Methods Osteoporotic fractures (OP group, n = 10) or osteoarthritis without osteoporosis (control group, n = 10) were selected as subjects in this study. Quantitative analysis of gene expression was performed by RT-PCR. Western blot was used to determine the expression levels of protein forkhead O1 (FOXO1). Bioinformatics analyses and luciferase reporter assay were used to verify the downstream target of miR-532-5p. Results Compared with the non-osteoporotic controls, miR-532-5p was upregulated in osteoporotic samples, and expression of miR-532-5p was downregulated in the osteogenic C2C12 cell model. Overexpression of miR-532-5p resulted in decreased expression levels of key osteoblast markers, including alkaline phosphatase (ALP), osteocalcin (OC), and collagen type I alpha 1 (COL1A1). The inhibitory results of miR-532-5p were reversed. MiR-532-5p contained a putative FOXO1 binding site. Moreover, miR-532-5p inhibited the expression of FOXO1, and overexpression of FOXO1 inhibited the effect of miR-532-5p on osteoblast markers. Conclusions MiR-532-5p can provide references to osteoporosis by regulating the expression of FOXO1 and osteoblast differentiation. MiR-532-5p might serve as a therapeutic target for osteoporosis.

Background: MicroRNAs (miRNAs) are critical regulators in osteogenesis and cartilage formation. This study was designed to investigate whether miR-532-5p plays a role in the regulation of osteoporosis.Methods: Osteoporotic fractures (OP group, n = 10) or osteoarthritis without osteoporosis (control group, n = 10) were selected as subjects in this study. Quantitative analysis of gene expression was performed by RT-PCR. Western blot was used to determine the expression levels of protein forkhead O1 (FOXO1). Bioinformatics analyses and luciferase reporter assay were used to verify the downstream target of miR-532-5p.Results: Compared with the non-osteoporotic controls, miR-532-5p was upregulated in osteoporotic samples, and expression of miR-532-5p was downregulated in the osteogenic C2C12 cell model. Overexpression of miR-532-5p resulted in decreased expression levels of key osteoblast markers, including alkaline phosphatase (ALP), osteocalcin (OC), and collagen type I alpha 1 (COL1A1). The inhibitory results of miR-532-5p were reversed. MiR-532-5p contained a putative FOXO1 binding site. Moreover, miR-532-5p inhibited the expression of FOXO1, and overexpression of FOXO1 inhibited the effect of miR-532-5p on osteoblast markers.Conclusions: MiR-532-5p can provide references to osteoporosis by regulating the expression of FOXO1 and osteoblast differentiation. MiR-532-5p might serve as a therapeutic target for osteoporosis. [ABSTRACT FROM AUTHOR]