Lactate‐Driven Epigenetic Reprogramming of Osteogenesis: <scp>H3K18</scp> Lactylation Activates <scp>m6A</scp> / <scp>YTHDF1</scp> ‐Dependent <scp>YAP1</scp> Signaling to Combat Bone Loss
A-dependent translation of YAP1, as confirmed by RIP-qPCR and dual-luciferase reporter assays. Elevation of lactate levels increased H3K18la, upregulated the YTHDF1-YAP1 axis, improved BMSC osteogenesis, and alleviated osteoporotic phenotypes in OVX mice. In addition, p300 was shown to regulate H3K18la levels and influence osteogenic differentiation in BMSCs. Collectively, this study identifies a previously unrecognized "lactate-H3K18la-YTHDF1-YAP1" regulatory axis, linking metabolic status to epigenetic modification and translational control in osteoporosis, and provides new mechanistic insights and potential therapeutic targets for bone loss.
Authors
- Xiaolong Yu (ORCID: https://orcid.org/0000-0003-4078-1350)
- Xuqiang Liu (ORCID: https://orcid.org/0000-0003-3361-8969)
- Qi Xu (ORCID: https://orcid.org/0000-0001-9311-213X)
- Haibo Zhan
- S Y Zhang
- Bin Zhang
- Meisong Zhu
- Jiawei Hu
- Song Wang
- Xuwen Luo
Institutions
- Shangrao Normal University (CN)
- Nanchang University (CN)
- First Affiliated Hospital of Jiangxi Medical College (CN)
- Nanchang Institute of Science & Technology (CN)
- First Affiliated Hospital of Nanchang University (CN)
Publication Details
- Journal
- The FASEB Journal
- Published
- 2026-04-25
- DOI
- https://doi.org/10.1096/fj.202502919rr
- Primary Topic
- Hippo pathway signaling and YAP/TAZ
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China