ArticleNature communications2023
Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed.
- The role of sleep and circadian rhythms in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Review
- Posture management for neck pain: identification and quantification of associated factors based on a multicentre cross-sectional study in China.Journal of global health · 2026Observational
- Melatonin rhythm-mimicking smart hydrogel for circadian clock regulation and promotion of intervertebral disc regeneration.Materials today. Bio · 2026Article
- Circadian rhythm: The hidden "puppet master" behind musculoskeletal disorders.Journal of orthopaedic translation · 2026Review
- Circadian biology and exercise: the time to move.Life metabolism · 2026Review
- The Interplay Between Circadian Clocks and the Tumour Microenvironment in Breast Cancer.Cancers · 2026Review
- The role and implications of mammalian cellular circadian entrainment.FEBS letters · 2026Review
- A damaging mutation in COL6A3 alters the mechanobiologic response of chondrocytes derived from human induced pluripotent stem cells.Stem cell research & therapy · 2026Article
- The pivotal role and intervention strategies of BMAL1 mediated circadian clock dysregulation in intervertebral disc degeneration.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Cry2 prompts clock oscillation and temporomandibular joint homeostasis under mechanical loading.Bone & joint research · 2026Article
- Intratendon bioimpedance spectroscopy: a first step exploring reliability and sensitivity to change.PeerJ · 2026Article
- Circadian regulation of osteoclast lysosomal-resorption machinery: implications for osteoporosis therapy.Frontiers in cell and developmental biology · 2026Review
- A Multidimensional Definition of Pre-Osteoarthritis: Toward 21st-Century Subclinical Detection and Targeted Intervention.International journal of molecular sciences · 2025Review
- Programmable chronogenetic gene circuits for self-regulated circadian delivery of biologic drugs.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Article
- Pharmacist-Driven Chondroprotection in Osteoarthritis: A Multifaceted Approach Using Patient Education, Information Visualization, and Lifestyle Integration.Pharmacy (Basel, Switzerland) · 2025Review
- Inhibiting the REV-ERBα expression protects against mechanical overloading-induced cartilage clock disruption and osteoarthritis progression.Journal of orthopaedic translation · 2025Article
- Article
- Progressing future osteoarthritis treatment toward precision medicine: integrating regenerative medicine, gene therapy and circadian biology.Experimental & molecular medicine · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding). The presence of tissue niche-dependent physiological time cues has been proposed, allowing tissues the ability of circadian phase adjustment based on local signals. However, to date, such stimuli have remained elusive. Here we show that daily patterns of mechanical loading and associated osmotic challenge within physiological ranges reset circadian clock phase and amplitude in cartilage and intervertebral disc tissues in vivo and in tissue explant cultures. Hyperosmolarity (but not hypo-osmolarity) resets clocks in young and ageing skeletal tissues and induce genome-wide expression of rhythmic genes in cells. Mechanistically, RNAseq and biochemical analysis revealed the PLD2-mTORC2-AKT-GSK3β axis as a convergent pathway for both in vivo loading and hyperosmolarity-induced clock changes. These results reveal diurnal patterns of mechanical loading and consequent daily oscillations in osmolarity as a bona fide tissue niche-specific time cue to maintain skeletal circadian rhythms in sync.
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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.