ArticleMolecular therapy. Nucleic acids2023
BMAL1-TTK-H2Bub1 loop deficiency contributes to impaired BM-MSC-mediated bone formation in senile osteoporosis.
Article in Molecular therapy. Nucleic acids, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).Molecular medicine reports · 2026Review
- Targeting Endogenous Lipophagy: A Novel Strategy to Enhance MSC Osteogenesis and Mineralization for Senile Osteoporosis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- BMAL1 Proteostasis, Circadian Dysfunction, and Ferroptotic Vulnerability in Osteoporosis: Current Evidence and Experimental Priorities.Calcified tissue international · 2026Review
- Comprehensive bioinformatics analysis and experimental validation reveal the role of circadian rhythm-related genes in the crosstalk between osteoporosis and atherosclerosis.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- BHLHE41-SLC7A11 transcriptional axis and chromatin remodeling signatures in osteogenic-lineage disulfidptosis-like stress in osteoporosis.Frontiers in genetics · 2026Article
- Review
- Signaling pathway mechanisms of circadian clock gene Bmal1 regulating bone and cartilage metabolism: a review.Bone research · 2025Review
- Iron-dependent KDM4D activity controls the quiescence-activity balance of MSCs via the PI3K-Akt-Foxo1 pathway.Cellular and molecular life sciences : CMLS · 2024Article
- Natural Compounds for Preventing Age-Related Diseases and Cancers.International journal of molecular sciences · 2024Review
- Emerging Role and Mechanism of Mesenchymal Stem Cells-Derived Extracellular Vesicles in Rheumatic Disease.Journal of inflammation research · 2024Review
- ED-71 Ameliorates Bone Loss in Type 2 Diabetes Mellitus by Enhancing Osteogenesis Through Upregulation of the Circadian Rhythm Coregulator BMAL1.Drug design, development and therapy · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the aging process, the reduced osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) results in decreased bone formation, which contributes to senile osteoporosis. Previous studies have confirmed that interrupted circadian rhythm plays an indispensable role in age-related disease. However, the mechanism underlying the impaired osteogenic differentiation of BM-MSCs during aging and its relationship with interrupted circadian rhythm remains unclear. In this study, we confirmed that the circadian rhythm was interrupted in aging mouse skeletal systems. The level of the core rhythm component BMAL1 but not that of CLOCK in the osteoblast lineage was decreased in senile osteoporotic specimens from both human and mouse. BMAL1 targeted TTK as a circadian-controlled gene to phosphorylate MDM2 and regulate H2Bub1 level, while H2Bub1 in turn regulated the expression of BMAL1. The osteogenic capacity of BM-MSCs was maintained by a positive loop formed by BMAL1-TTK-MDM2-H2Bub1. Furthermore, we demonstrated that using bone-targeting recombinant adeno-associated virus 9 (rAAV9) to enhance Bmal1 or Ttk might have a therapeutic effect on senile osteoporosis and delays bone repair in aging mice. In summary, our study indicated that targeting the BMAL1-TTK-MDM2-H2Bub1 axis via bone-targeting rAAV9 might be a promising strategy for the treatment of senile osteoporosis.
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