ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Physiological loading of joints prevents cartilage degradation through CITED2.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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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
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Are Altered Knee Joint Biomechanics Associated with Future Post-Traumatic Osteoarthritis Outcomes? A Systematic Review and Meta-Analysis of Longitudinal Studies.Sports medicine (Auckland, N.Z.) · 2025Pooled it
- Modifying loading during gait leads to biochemical changes in serum cartilage oligomeric matrix protein concentrations in a subgroup of individuals with anterior cruciate ligament reconstruction.Clinical rheumatology · 2024Trial
- Immediate Biochemical Changes After Gait Biofeedback in Individuals With Anterior Cruciate Ligament Reconstruction.Journal of athletic training · 2020Trial
- Two cycles of plasma rich in growth factors (PRGF-Endoret) intra-articular injections improve stiffness and activities of daily living but not pain compared to one cycle on patients with symptomatic knee osteoarthritis.Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA · 2018Trial
- Combination of Intra-Articular and Intraosseous Injections of Platelet Rich Plasma for Severe Knee Osteoarthritis: A Pilot Study.BioMed research international · 2016Trial
- Critical Overview of Molecular Insights into Osteoarthritis and Therapeutic Targets: Cytokines, RANKL, MMPs, Adipokines and Phosphate Dysregulation.International journal of molecular sciences · 2026Review
- The post-operative loading regimen influences the regenerative potential of a biomimetic osteochondral scaffold.Biomedical engineering online · 2025Article
- Association of activity with the risk of developing musculoskeletal pain in the All of Us research program.The journal of pain · 2025Article
- Aberrant Gait Biomechanics Linked to Cartilage Changes After ACL Reconstruction in Those With High Body Mass Index.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Article
- Lower Extremity Mechanical Energetics During Walking 6 Months Following Anterior Cruciate Ligament Reconstruction.Scandinavian journal of medicine & science in sports · 2025Article
- Impact of Abnormal Mechanical Stress on Chondrocyte Death in Osteoarthritis.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- Weight-Bearing Physical Activity, Lower-Limb Muscle Mass, and Risk of Knee Osteoarthritis.JAMA network open · 2024Article
- Body mass affects kinetic symmetry and inflammatory markers in adolescent knees during gait.Clinical biomechanics (Bristol, Avon) · 2023Article
- Exercise to Mend Aged-tissue Crosstalk in Bone Targeting Osteoporosis & Osteoarthritis.Seminars in cell & developmental biology · 2022Review
- The potential roles of JAK/STAT signaling in the progression of osteoarthritis.Frontiers in endocrinology · 2022Review
- Influence of the Mechanical Environment on the Regeneration of Osteochondral Defects.Frontiers in bioengineering and biotechnology · 2021Review
- Cartilage tissue engineering for obesity-induced osteoarthritis: Physiology, challenges, and future prospects.Journal of orthopaedic translation · 2021Review
- Biomechanical effects of manipulating peak vertical ground reaction force throughout gait in individuals 6-12 months after anterior cruciate ligament reconstruction.Clinical biomechanics (Bristol, Avon) · 2020Article
- Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes.International journal of molecular sciences · 2020Article
- Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models.Frontiers in bioengineering and biotechnology · 2020Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Both overuse and disuse of joints up-regulate matrix metalloproteinases (MMPs) in articular cartilage and cause tissue degradation; however, moderate (physiological) loading maintains cartilage integrity. Here, we test whether CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), a mechanosensitive transcriptional coregulator, mediates this chondroprotective effect of moderate mechanical loading. In vivo, hind-limb immobilization of Sprague-Dawley rats up-regulates MMP-1 and causes rapid, histologically detectable articular cartilage degradation. One hour of daily passive joint motion prevents these changes and up-regulates articular cartilage CITED2. In vitro, moderate (2.5 MPa, 1 Hz) intermittent hydrostatic pressure (IHP) treatment suppresses basal MMP-1 expression and up-regulates CITED2 in human chondrocytes, whereas high IHP (10 MPa) down-regulates CITED2 and increases MMP-1. Competitive binding and transcription assays demonstrate that CITED2 suppresses MMP-1 expression by competing with MMP transactivator, Ets-1 for its coactivator p300. Furthermore, CITED2 up-regulation in vitro requires the p38δ isoform, which is specifically phosphorylated by moderate IHP. Together, these studies identify a novel regulatory pathway involving CITED2 and p38δ, which may be critical for the maintenance of articular cartilage integrity under normal physical activity levels.
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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.