Synergistic epigenetic modulation by 5-aza-2'-deoxycytidine and Wnt3a drives osteogenic trans-differentiation of 3T3-L1 pre-adipocytes through Ywhah and Ywhae .
Park SG., Kim KT., Kim WJ., Kim S., Cho YD.
Prospective Study, published in Epigenomics (2025) — summary generated from the PubMed abstract.
Early human evidence such as case series or small samples is exploring possible benefits.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Prospective Study
- Journal
- Epigenomics (2025)
- Country
- England
- Reported sample size
- —
- Source database
- PubMed
- PMID
- 40792537
- DOI
- 10.1080/17501911.2025.2544513
Abstract (original English)
In 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. 3T3‑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. Transcriptomic 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 ( Ywhah) and Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Epsilon ( Ywhae) emerged as key regulators, whose knockdown notably enhanced Alpl expression even without 5azaC. Combining 5azaC-induced demethylation with Wnt3a is a potent strategy to redirect pre-adipocytes
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
Evidence level
Early human evidence such as case series or small samples is exploring possible benefits.
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