Dnmt1 determines bone length by regulating energy metabolism of growth plate chondrocytes

Yuta Yanagihara, Masatomo Takahashi, Yoshihiro Izumi, Tomofumi Kinoshita, Masaki Takao, Takeshi Bamba and Yuuki Imai ()
Additional contact information
Yuta Yanagihara: Ehime University
Masatomo Takahashi: Kyushu University
Yoshihiro Izumi: Kyushu University
Tomofumi Kinoshita: Ehime University Graduate School of Medicine
Masaki Takao: Ehime University Graduate School of Medicine
Takeshi Bamba: Kyushu University
Yuuki Imai: Ehime University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Chondrocytes differentiated from mesenchymal stem cells play a role in determining skeletal patterns by ossification. However, the mechanism by which maintenance DNA methylation in chondrocytes regulates differentiation and skeletal formation is unclear. In the Musculoskeletal Knowledge Portal, Dnmt1 is significantly associated with Height. Long bones in Dnmt1-deficient (Dnmt1ΔPrx1) mouse limbs are significantly shortened due to decreased chondrocyte proliferation and accelerated differentiation. Integrated analysis of RNA-Seq and MBD-Seq reveals that reduced DNA methylation in Dnmt1ΔPrx1 chondrocytes leads to increased expression of genes related to energy metabolism and to ossification. Metabolomic analyses confirm that Dnmt1ΔPrx1 chondrocytes had increased levels of nearly all energy metabolites. These results indicate that Dnmt1-mediated maintenance of DNA methylation governs chondrocyte differentiation by regulating energy metabolism through both gene expression and modulation of metabolite supplies. Taken together, this study suggests that appropriate DNA methylation status in chondrocytes can orchestrate growth plate mineralization and subsequently determine bone length.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65145-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65145-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-65145-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().