Active vitamin D protects against osteoporosis by promoting VDR-dependent CDK2 transcription and P27 degradation
Clicks: 6
ID: 324895
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Emerging Content
1.5
/100
6 views
2 readers
AI Quality Assessment
Not analyzed
Readership in this journal
EmergingRanked #46 of 96 articles by views in european journal of endocrinology
Most read
Least read
Bar heights use a square-root scale.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Abstract Objective Osteoporosis is associated with reduced active vitamin D, but the molecular basis remains incompletely understood. This study investigated how active vitamin D preserves skeletal homeostasis and prevents bone loss. Design Experimental mechanistic study using genetically modified mouse models and bone marrow mesenchymal stem cells (BMSCs). Methods Mice with reduced active vitamin D production were examined for bone mass, skeletal ageing, and osteogenic capacity. Mouse and human BMSCs were used to assess proliferation, osteogenic differentiation, and molecular signalling. Gene expression, protein turnover, and pathway analyses determined how active vitamin D regulates cell-cycle control in skeletal progenitors. Genetic deletion studies tested the functional contribution of P27 to bone loss. Results Active vitamin D protected against osteoporosis by activating a vitamin D receptor (VDR)-dependent pathway that increased cyclin-dependent kinase 2 (CDK2) expression and promoted P27 degradation in BMSCs. Loss of this signalling caused P27 accumulation, reduced stem-cell proliferation, impaired osteogenic differentiation, and enhanced skeletal senescence, leading to bone loss. Active vitamin D promoted P27 phosphorylation at threonine 187 and its degradation via the ubiquitin-proteasome pathway. Importantly, P27 deletion partially rescued the osteoporotic phenotype in mice with reduced active vitamin D production. Conclusions Active vitamin D maintains bone integrity through a VDR-dependent mechanism that enhances CDK2 expression and promotes P27 degradation in BMSCs. These findings identify a previously unrecognised mechanism linking vitamin D signalling to skeletal ageing and suggest that targeting P27 turnover may offer a therapeutic strategy, provided tissue-specific approaches mitigate the oncogenic risks of P27 manipulation.
| Reference Key |
openalex_W7202382773
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Fangrong Xu, Quan Liu, Mingxin Huang, Jing Wang, David Goltzman, Bingjie Gu, Dengshun Miao |
| Journal | european journal of endocrinology |
| Year | 2026 |
| DOI |
10.1093/ejendo/lvag152
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.