ArticleEpigenomics2025
Synergistic epigenetic modulation by 5-aza-2'-deoxycytidine and Wnt3a drives osteogenic trans-differentiation of 3T3-L1 pre-adipocytes through
Article in Epigenomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- DNA Methylation Dynamics inBiomolecules · 2026Article
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5 authors.
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Abstract
backgroundIn elderly patients, bone regeneration is impeded by age-related shifts in mesenchymal stem cell differentiation propensity toward adipogenesis over osteogenesis. We investigated whether DNA demethylation by 5‑aza‑2'‑deoxycytidine (5azaC) synergizes with Wnt Family Member 3A (Wnt3a) signaling to induce osteogenic potential in 3T3‑L1 pre-adipocytes, generating osteoblast-like cells.
methods3T3‑L1 pre-adipocytes were treated with 5azaC and/or Wnt3a. Osteogenic differentiation was assessed via ALP activity, mineralization assays, and marker expression. Transcriptomic and epigenomic profiling were performed and compared with MC3T3-E1 cells. Functional relevance of candidate genes was examined using siRNA knockdown.
resultsTranscriptomic and epigenomic profiling revealed that 5azaC and Wnt3a co-treatment induced broader gene expression and methylation changes than either treatment alone, closely resembling the osteogenic profile of MC3T3-E1 pre-osteoblasts. Among the overlapping differentially methylated and steadily expressed genes, Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Eta (
conclusionsCombining 5azaC-induced demethylation with Wnt3a is a potent strategy to redirect pre-adipocytes toward osteogenesis. Identification of key targets like Ywhah and Ywhae provides mechanistic insight into trans-differentiation and suggests therapeutic potential for bone regeneration, particularly in elderly periodontal patients.
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