Bmi‐1 Epigenetically Orchestrates Osteogenic and Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells to Delay Bone Aging

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Abstract: With the increase in the aging population, senile osteoporosis (SOP) has become a major global public health concern. Here, it is found that Prx1 and Bmi‐1 co‐localized in trabecular bone, bone marrow cavity, endosteum, and periosteum. Prx1‐driven Bmi‐1 knockout in bone‐marrow mesenchymal stem cells (BMSCs) reduced bone mass and increased bone marrow adiposity by inhibiting osteoblastic bone formation, promoting osteoclastic bone resorption, downregulating the proliferation and osteogenic differentiation of BMSCs, and upregulating the adipogenic differentiation of BMSCs. However, Prx1‐driven Bmi‐1 overexpression showed a contrasting phenotype to Prx1‐driven Bmi‐1 knockout in BMSCs. Regarding mechanism, Bmi‐1‐RING1B bound to DNMT3A and promoted its ubiquitination and inhibited DNA methylation of Runx2 at the region from 45047012 to 45047313 bp, thus promoting the osteogenic differentiation of BMSCs. Moreover, Bmi‐1‐EZH2 repressed the transcription of Cebpa by promoting H3K27 trimethylation at the promoter region −1605 to −1596 bp, thus inhibiting the adipogenic differentiation of BMSCs. It is also found that Prx1‐driven Bmi‐1 overexpression rescued the SOP induced by Prx1‐driven Bmi‐1 knockout in BMSCs. Thus, Bmi‐1 functioned as a hub protein in the epigenetic regulation of BMSCs differentiation to delay bone aging. The Prx1‐driven Bmi‐1 overexpression in BMSCs can be used as an approach for the translational therapy of SOP.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Bmi‐1 Epigenetically Orchestrates Osteogenic and Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells to Delay Bone Aging ; day:03 ; month:09 ; year:2024 ; extent:21
Advanced science ; (03.09.2024) (gesamt 21)

Urheber
Zhao, Jingyu
Chen, Ao
Wang, Rong
Qiu, Dong
Chen, Haiyun
Li, Jiyu
Zhang, Jin'ge
Wang, Tianxiao
Wang, Yue
Lin, Yujie
Zhou, Jiawen
Du, Yifei
Yuan, Hua
Zhang, Yongjie
Miao, Dengshun
Wang, Yuli
Jin, Jianliang

DOI
10.1002/advs.202404518
URN
urn:nbn:de:101:1-2409031429077.032245619258
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:29 MESZ

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Beteiligte

  • Zhao, Jingyu
  • Chen, Ao
  • Wang, Rong
  • Qiu, Dong
  • Chen, Haiyun
  • Li, Jiyu
  • Zhang, Jin'ge
  • Wang, Tianxiao
  • Wang, Yue
  • Lin, Yujie
  • Zhou, Jiawen
  • Du, Yifei
  • Yuan, Hua
  • Zhang, Yongjie
  • Miao, Dengshun
  • Wang, Yuli
  • Jin, Jianliang

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