Youthfulness of marrow Adipoq⁺ cells maintained by Cbfβ facilitates stem cell-based bone repair.

Authors

Tiannan Huang, Shali Wu, Wei Qian, Ruiying Chen, Erman Chen, Meizhu Wang, Cui Zhang, Chenhe Zhou, Luyang Yu, Mengjie Wu, Yi-Ping Li, Mengrui Wu

Published in

Bone research. Volume 14. Issue 1. Aug 10, 2026. Epub Aug 10, 2026.

Abstract

Exhaustion of skeletal stem and progenitor cells (SSPCs) drives age-related delays in fracture repair, yet the upstream regulators of SSPC maintenance are unclear. We identify that core-binding factor β (Cbfβ) in bone marrow Adipoq⁺ cells (BMACs) is essential for maintaining SSPC number and function. Cbfβ deletion in BMACs (CKO) leads to SSPC depletion, including periosteal populations, and impairs bicortical fracture healing in mice. Multi-omics (RNA-seq, CUT&Tag-seq, and ATAC-seq) reveal that Cbfβ preserves chromatin accessibility at DNA repair loci, maintaining genomic stability, preventing BMAC senescence, and mitigating the senescence-associated secretory phenotype (SASP). Senolytic therapy alleviates BMAC senescence, restores SSPC populations, and improves bone repair in CKO mice. In both humans and mice, Cbfβ expression declines with aging, accompanied by increased BMAC senescence. AAV-mediated Cbfβ overexpression restores aging-related bone repair and SSPC decline. These findings reveal a novel mechanism in which Cbfβ in BMACs regulates SSPC maintenance via a senescence/SASP axis, offering a potential therapeutic strategy for age-related bone repair deficits.

PMID:
42575886
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

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