ArticleBone research2022
Restoring the dampened expression of the core clock molecule BMAL1 protects against compression-induced intervertebral disc degeneration.
Article in Bone research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- 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
- Melatonin rhythm-mimicking smart hydrogel for circadian clock regulation and promotion of intervertebral disc regeneration.Materials today. Bio · 2026Article
- Targeting AMPK signaling in nucleus pulposus cells ameliorates spaceflight microgravity-induced intervertebral disc degeneration.Cell death and differentiation · 2026Article
- Disruption of YAP biomolecular condensates by mechanical stress drives intervertebral disc vascularization.Science advances · 2026Article
- In vivo 3D kinematic analysis of cervical facet joints under physiological loading in healthy individuals.Bone & joint research · 2026Article
- Macrophage-derived legumain ameliorates excessive mechanical stress-induced ferroptosis of nucleus pulposus cells and intervertebral disc degeneration via integrin αvβ3-Hippo signaling.Cellular & molecular biology letters · 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
- Piezo1 Upregulation in Monocyte-Derived Macrophages Impairs Post-Myocardial Infarction Cardiac Repair via Defective Efferocytosis and Enhanced Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Circadian regulation in intervertebral disc degeneration: mechanisms and clinical implications.Frontiers in molecular biosciences · 2026Review
- Dual roles of circadian clock proteins in development and adult homeostasis.Npj biological timing and sleep · 2026Review
- Circadian control of immune homeostasis in cardiovascular health and disease.Frontiers in immunology · 2026Review
- Review
- Achilles tendinopathy treatment via circadian rhythm regulation.Journal of advanced research · 2025Article
- Inhibiting the REV-ERBα expression protects against mechanical overloading-induced cartilage clock disruption and osteoarthritis progression.Journal of orthopaedic translation · 2025Article
- Article
- Reprogramming to restore youthful epigenetics of senescent nucleus pulposus cells for mitigating intervertebral disc degeneration and alleviating low back pain.Bone research · 2025Article
- Signaling pathway mechanisms of circadian clock gene Bmal1 regulating bone and cartilage metabolism: a review.Bone research · 2025Review
- Identification of Potential Targets for EGFR-Regulated Nucleus Pulposus Degeneration Using Single-Cell RNA Sequencing and Machine Learning.Journal of inflammation research · 2025Article
- Region-specific mitophagy in nucleus pulposus, annulus fibrosus, and cartilage endplate of intervertebral disc degeneration: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
Abstract
The circadian clock participates in maintaining homeostasis in peripheral tissues, including intervertebral discs (IVDs). Abnormal mechanical loading is a known risk factor for intervertebral disc degeneration (IDD). Based on the rhythmic daily loading pattern of rest and activity, we hypothesized that abnormal mechanical loading could dampen the IVD clock, contributing to IDD. Here, we investigated the effects of abnormal loading on the IVD clock and aimed to inhibit compression-induced IDD by targeting the core clock molecule brain and muscle Arnt-like protein-1 (BMAL1). In this study, we showed that BMAL1 KO mice exhibit radiographic features similar to those of human IDD and that BMAL1 expression was negatively correlated with IDD severity by systematic analysis based on 149 human IVD samples. The intrinsic circadian clock in the IVD was dampened by excessive loading, and BMAL1 overexpression by lentivirus attenuated compression-induced IDD. Inhibition of the RhoA/ROCK pathway by Y-27632 or melatonin attenuated the compression-induced decrease in BMAL1 expression. Finally, the two drugs partially restored BMAL1 expression and alleviated IDD in a diurnal compression model. Our results first show that excessive loading dampens the circadian clock of nucleus pulposus tissues via the RhoA/ROCK pathway, the inhibition of which potentially protects against compression-induced IDD by preserving BMAL1 expression. These findings underline the importance of the circadian clock for IVD homeostasis and provide a potentially effective therapeutic strategy for IDD.
Identifiers
What OpenQuestion holds
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.