Research Paper Volume 13, Issue 14 pp 18257—18273
The lncRNA H19/miR-541-3p/Wnt/β-catenin axis plays a vital role in melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells
- 1 Department of Center of Pediatric Dentistry, Jinan Stomatology Hospital, Jinan 250001, Shandong Province, China
- 2 Department of Oral and Maxillofacial Surgery, Jinan Stomatology Hospital, Jinan 250001, Shandong Province, China
Received: January 14, 2021 Accepted: May 14, 2021 Published: July 26, 2021https://doi.org/10.18632/aging.203267
How to Cite
Copyright: © 2021 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Implant dentures become the first choice for denture restoration in patients with tooth loss. However, oral implants often fail in osteoporosis (OP) patients. Melatonin (MT) induces osteogenic differentiation of bone mesenchymal stem cells (BMSCs), suggesting its therapeutic potential in OP treatment. Long non-coding RNA H19 induces osteogenic differentiation of BMSCs, while its regulatory mechanism in MT-involved osteogenic and adipogenic differentiation of BMSCs remains elusive. Ovariectomized (OVX) rat was used to construct an OP model, and bone quality was assessed. Meanwhile, the expression of H19, miR-541-3p, MT and adiponectin (APN) was examined by quantitative reverse transcription-PCR (qRT-PCR) or ELISA. The adipogenic and osteogenic differentiation of BMSCs were determined by oil red O staining and alizarin red S staining, respectively. The targeting relationships between H19, miR-541-3p and APN mRNA were predicted by bioinformatics and confirmed by RNA immunoprecipitation and dual-luciferase reporter assay. The results showed that MT, H19 and APN were down-regulated, while miR-541-3p was up-regulated in the OVX rat model. At the cellular level, MT reduced adipogenic differentiation, heightened osteogenic differentiation of BMSCs, and activated Wnt/β-catenin pathway, which were reversed by the MT2 selective inhibitor 4-P-PDOT. Overexpressing H19 facilitated the osteogenic differentiation and inhibited the adipogenic differentiation of BMSCs mediated by MT, while H19 knockdown or overexpressing miR-541-3p had the opposite effect. Moreover, H19 functioned as a competitive endogenous RNA and sponged miR-541-3p, and miR-541-3p targeted APN. Overall, MT modulates the osteogenic and adipogenic differentiation of BMSCs by mediating H19/miR-541-3p/APN axis, providing a new reference for the targeted therapy of OP.