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  • Title: lncRNA IGF2-AS promotes the osteogenic differentiation of bone marrow mesenchymal stem cells by sponging miR-3,126-5p to upregulate KLK4.
    Author: Tang JZ, Zhao GY, Zhao JZ, Di DH, Wang B.
    Journal: J Gene Med; 2021 Oct; 23(10):e3372. PubMed ID: 34101307.
    Abstract:
    BACKGROUND: Osteoporosis (OP) is a bone disease characterized by reduced amount and quality of bone. This study was designed to explore the role and mechanism of lncRNA IGF2-AS in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: Human lncRNA and miRNA microarray analyses were performed to measure the differential expression levels of lncRNAs and miRNAs in undifferentiated and osteogenically differentiated BMSCs. lncRNA IGF2-AS, miR-3,126-5p, and KLK4 levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Osteogenic differentiation of BMSCs was assessed by alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS). Protein levels of osterix (Osx), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2) were examined by RT-PCR and western blot assays. The binding relationship between miR-3,126-5p and lncRNA IGF2-AS or KLK4 was predicted by TargetScan (http://www.targetscan.org/vert_72/) and then verified with a dual-luciferase reporter assay. RESULTS: lncRNA IGF2-AS and KLK4 were highly expressed and miR-3,126-5p was weakly expressed in osteogenically differentiated BMSCs. Moreover, lncRNA IGF2-AS overexpression enhanced the osteogenic differentiation of BMSCs. In contrast, lncRNA IGF2-AS knockdown showed the opposite trend. Moreover, miR-3,126-5p overexpression abolished the lncRNA IGF2-AS-mediated osteogenic differentiation of BMSCs. lncRNA IGF2-AS functions as a sponge of miR-3,126-5p to regulate KLK4 expression. CONCLUSION: lncRNA IGF2-AS enhances the osteogenic differentiation of BMSCs by modulating the miR-3,126-5p/KLK4 axis, suggesting a promising therapeutic target for bone-related diseases.
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