Abstract
N6-methyladenosine (m6A) modification plays a crucial role in the progression of osteoporosis (OP). The study aimed to explore the effects of methyltransferase-like 3 (METTL3) in OP. The levels of METTL3, LINC00657, miR-144-3p and BMPR1B were detected using qPCR. Osteogenesis was assessed using alizarin red and alkaline phosphatase (ALP) staining assays. The protein expression of Bglap, Runx2 and Col1a1 was measured by western blot. The targets of LINC00657 and miR-144-3p were screened by bioinformatic analysis. The interaction between miR-144-3p and LINC00657 or BMPR1B was analyzed by dual-luciferase reporter assay and RNA pull-down assay. The results showed that METTL3 was downregulated in OP. METTL3 mediated m6A methylation of LINC00657 to promote the development of osteogenesis. Further study indicated that LINC00657 functioned as a ceRNA to upregulate BMPR1B via sponging miR-144-3p. Additionally, BMPR1B knockdown alleviated the effects of METTL3 on osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Taken together, METTL3 facilitated osteogenic differentiation of BMSCs via the LINC00657/miR-144-3p/BMPR1B axis. Our findings may provide a novel insight of m6A methylation in the development of OP.
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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The collection of calcified and normal aortic valve tissues from all subjects was approved by the Ethics Committee of the Shanghai Jiao Tong University Affiliated Sixth People's Hospital (No.47204658).
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Peng, J., Zhan, Y. & Zong, Y. METTL3-mediated LINC00657 promotes osteogenic differentiation of mesenchymal stem cells via miR-144-3p/BMPR1B axis. Cell Tissue Res 388, 301–312 (2022). https://doi.org/10.1007/s00441-022-03588-y
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DOI: https://doi.org/10.1007/s00441-022-03588-y