METTL3 inhibits osteoporosis by promoting osteoblast differentiation through m6A-mediated activation of the FZD3/RUNX1 signaling axis
Abstract
Background: Osteoporosis (OP) is a well-known metabolic bone disorder. This paper was to unveil the mechanism of the m6A methylation transferase METTL3 in OP.
Methods: Through literature search and sample analysis, m6A methylation transferase METTL3 was selected as the study object. Ovariectomy (OVX) was leveraged to build a mouse model of OP. The OVX mouse model was evaluated by RT-qPCR, Western blot, and HE staining. The oe-METTL3 or FZD3 lentiviral vectors were delivered into MC3T3-E1 cells and BMMs or injected intraperitoneally into OVX mice to observe the differentiation levels of osteoblasts and osteoclasts, as well as alterations in OP symptoms. Quantitative m6A analysis and RIP assays were performed to verify the downstream gene FZD3 of METTL3, and pathway enrichment was performed to analyze the signaling pathways regulated by FZD3. Rescue experiments were performed to verify the role of METTL3 on osteoblast and osteoclast differentiation through the FZD3/RUNX1 axis.
Results: METTL3 and FZD3 were downregulated in osteoporotic mice. Overexpression of METTL3 or FZD3 in OVX mice promoted osteoblasts and osteogenesis and blocked osteoclast differentiation and bone resorption. METTL3 regulates FZD3 expression via m6A modification. FZD3 promoted osteoblast differentiation and bone formation while inhibiting osteoclast differentiation and bone resorption by regulating RUNX1, a protein downstream of the Wnt pathway. Overexpression of FZD3 partially reversed the effect of…
Read the paper
Related studies
- Irisin Enhances Osteoblast DifferentiationIn Vitro
- Glucocorticoids suppress Wnt16 expression in osteoblasts in vitro and in vivo
- Interaction between Schwann Cells and Osteoblasts In Vitro
- Administration of cinnamaldehyde promotes osteogenesis in ovariectomized rats and differentiation of osteoblast in vitro
- The Effect of the Major Components of Fructus Cnidii on Osteoblasts In Vitro
- Estrogen depletion alters osteogenic differentiation and matrix production by osteoblasts in vitro
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.