ArticleBMC musculoskeletal disorders2013
Knee loading reduces MMP13 activity in the mouse cartilage.
Article in BMC musculoskeletal disorders, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Roles of VWA1 and Rac2 in compensatory and decompensatory responses via FGF9/FGFR3 and p38 MAPK signaling pathways in condylar chondrocytes under distinct mechanical stress.Arthritis research & therapy · 2025Article
- Rho GTPase signaling in rheumatic diseases.iScience · 2022Review
- Overexpression of Lrp5 enhanced the anti-breast cancer effects of osteocytes in bone.Bone research · 2021Article
- Mechanical Loading-Driven Tumor Suppression Is Mediated by Lrp5-Dependent and Independent Mechanisms.Cancers · 2021Article
- Generation of the tumor-suppressive secretome from tumor cells.Theranostics · 2021Article
- Alpinetin Protects Chondrocytes and Exhibits Anti-Inflammatory Effects via the NF-κB/ERK Pathway for Alleviating Osteoarthritis.Inflammation · 2020Article
- Knee loading repairs osteoporotic osteoarthritis by relieving abnormal remodeling of subchondral bone via Wnt/β-catenin signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Low-level cyclic tibial compression attenuates early osteoarthritis progression after joint injury in mice.Osteoarthritis and cartilage · 2019Article
- Effects of Rolling-Sliding Mechanical Stimulation on Cartilage PreservedCellular and molecular bioengineering · 2019Article
- Mechanobiological Mechanisms of Load-Induced Osteoarthritis in the Mouse Knee.Journal of biomechanical engineering · 2019Article
- Finite-element analysis of the mouse proximal ulna in response to elbow loading.Journal of bone and mineral metabolism · 2019Article
- CITED2 mediates the cross-talk between mechanical loading and IL-4 to promote chondroprotection.Annals of the New York Academy of Sciences · 2019Article
- Mechanical loading mitigates osteoarthritis symptoms by regulating endoplasmic reticulum stress and autophagy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Collagen XI mutation lowers susceptibility to load-induced cartilage damage in mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2018Article
- Aliskiren has chondroprotective efficacy in a rat model of osteoarthritis through suppression of the local renin-angiotensin system.Molecular medicine reports · 2017Article
- Subcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling.Scientific reports · 2017Article
- Non-invasive Loading Model of Murine Osteoarthritis.Current rheumatology reports · 2016Review
- Knee loading inhibits osteoclast lineage in a mouse model of osteoarthritis.Scientific reports · 2016Article
- Rac1 Signaling Is Required for Anterior Second Heart Field Cellular Organization and Cardiac Outflow Tract Development.Journal of the American Heart Association · 2015Article
- Chondroprotective effects of Salubrinal in a mouse model of osteoarthritis.Bone & joint research · 2015Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundModerate loads with knee loading enhance bone formation, but its effects on the maintenance of the knee are not well understood. In this study, we examined the effects of knee loading on the activity of matrix metalloproteinase13 (MMP13) and evaluated the role of p38 MAPK and Rac1 GTPase in the regulation of MMP13.
methodsKnee loading (0.5-3 N for 5 min) was applied to the right knee of surgically-induced osteoarthritis (OA) mice as well as normal (non-OA) mice, and MMP13 activity in the femoral cartilage was examined. The sham-loaded knee was used as a non-loading control. We also employed primary non-OA and OA human chondrocytes as well as C28/I2 chondrocyte cells, and examined MMP13 activity and molecular signaling in response to shear at 2-20 dyn/cm².
resultsDaily knee loading at 1 N for 2 weeks suppressed cartilage destruction in the knee of OA mice. Induction of OA elevated MMP13 activity and knee loading at 1 N suppressed this elevation. MMP13 activity was also increased in primary OA chondrocytes, and this increase was attenuated by applying shear at 10 dyn/cm². Load-driven reduction in MMP13 was associated with a decrease in the phosphorylation level of p38 MAPK (p-p38) and NFκB (p-NFκB). Molecular imaging using a fluorescence resonance energy transfer (FRET) technique showed that Rac1 activity was reduced by shear at 10 dyn/cm² and elevated by it at 20 dyn/cm². Silencing Rac1 GTPase significantly reduced MMP13 expression and p-p38 but not p-NFκB. Transfection of a constitutively active Rac1 GTPase mutant increased MMP13 activity, while a dominant negative mutant decreased it.
conclusionsKnee loading reduces MMP13 activity at least in part through Rac1-mediated p38 MAPK signaling. This study suggests the possibility of knee loading as a therapy not only for strengthening bone but also preventing tissue degradation of the femoral cartilage.
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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.