ArticleCell research2021
Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration.
Article in Cell research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
66 citing papers in PubMed, 109 citations in OpenAlex.
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- The entropic view of aging: from thermodynamics to biology.Life medicine · 2026Article
- Vertebral BMSC-EVs under estrogen deficiency drive senescence-related mitochondrial dysfunction in endplate chondrocytes via MRPL1 mRNA delivery.Experimental & molecular medicine · 2026Article
- Basonuclin-2 promotes fracture repair through NuRD-dependent chromatin remodeling in periosteal stem cells.The EMBO journal · 2026Article
- Cry2 prompts clock oscillation and temporomandibular joint homeostasis under mechanical loading.Bone & joint research · 2026Article
- Article
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- The drug discovery and therapeutic nano-strategies targeting cellular senescence.Materials today. Bio · 2025Review
- Biomarkers of ageing of humans and non-human primates.Nature reviews. Molecular cell biology · 2025Review
- A comprehensive review of curcumin-based scaffolds in cartilage tissue engineering.Stem cell research & therapy · 2025Review
- Article
- Role of circadian CLOCK signaling in cellular senescence.Biogerontology · 2025Review
- Gene therapy strategies for aging intervention.Cell insight · 2025Review
- Progressing future osteoarthritis treatment toward precision medicine: integrating regenerative medicine, gene therapy and circadian biology.Experimental & molecular medicine · 2025Review
- RIG-I-driven CDKN1A stabilization reinforces cellular senescence.Science China. Life sciences · 2025Article
- Targeting NAMPT-OPA1 for treatment of senile osteoporosis.Aging cell · 2025Article
- Mechanical Cell Reprogramming on Tissue-Mimicking Hydrogels for Cancer Cell Transdifferentiation.Research (Washington, D.C.) · 2025Article
- Circadian system and aging: where both times interact.Frontiers in aging · 2025Review
- Embryonic Circadian Rhythm Establishment, Homeostasis, and Dysfunction During Organogenesis.Stem cells international · 2025Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence indicates an association between the circadian clock and the aging process. However, it remains elusive whether the deregulation of circadian clock proteins underlies stem cell aging and whether they are targetable for the alleviation of aging-associated syndromes. Here, we identified a transcription factor-independent role of CLOCK, a core component of the molecular circadian clock machinery, in counteracting human mesenchymal stem cell (hMSC) decay. CLOCK expression was decreased during hMSC aging. In addition, CLOCK deficiency accelerated hMSC senescence, whereas the overexpression of CLOCK, even as a transcriptionally inactive form, rejuvenated physiologically and pathologically aged hMSCs. Mechanistic studies revealed that CLOCK formed complexes with nuclear lamina proteins and KAP1, thus maintaining heterochromatin architecture and stabilizing repetitive genomic sequences. Finally, gene therapy with lentiviral vectors encoding CLOCK promoted cartilage regeneration and attenuated age-related articular degeneration in mice. These findings demonstrate a noncanonical role of CLOCK in stabilizing heterochromatin, promoting tissue regeneration, and mitigating aging-associated chronic diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.