{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:47:54Z","timestamp":1793908074435,"version":"4.8.0"},"reference-count":47,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":366,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F32 AR072478"],"award-info":[{"award-number":["F32 AR072478"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AR069619"],"award-info":[{"award-number":["P30 AR069619"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR056624"],"award-info":[{"award-number":["R01 AR056624"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR075737"],"award-info":[{"award-number":["R01 AR075737"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01 RX003375"],"award-info":[{"award-number":["I01 RX003375"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I21 RX003854"],"award-info":[{"award-number":["I21 RX003854"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","oarsijournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Osteoarthritis and Cartilage"],"published-print":{"date-parts":[[2024,1]]},"DOI":"10.1016\/j.joca.2023.09.012","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T11:40:29Z","timestamp":1697802029000},"page":"41-51","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"title":["Modulating mechanobiology as a therapeutic target for synovial fibrosis to restore joint lubrication"],"prefix":"10.1016","volume":"32","author":[{"given":"Edward D.","family":"Bonnevie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla R.","family":"Scanzello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Mauck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.joca.2023.09.012_bib1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/path.2277","article-title":"Cellular and molecular mechanisms of fibrosis","volume":"214","author":"Wynn","year":"2008","journal-title":"J Pathol"},{"key":"10.1016\/j.joca.2023.09.012_bib2","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.2353\/ajpath.2007.070112","article-title":"The myofibroblast: one function, multiple origins","volume":"170","author":"Hinz","year":"2007","journal-title":"Am J Pathol"},{"key":"10.1016\/j.joca.2023.09.012_bib3","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1161\/ATVBAHA.110.220061","article-title":"\u03b2-catenin mediates mechanically regulated, transforming growth factor-\u03b21-induced myofibroblast differentiation of aortic valve interstitial cells","volume":"31","author":"Chen","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1016\/j.joca.2023.09.012_bib4","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1165\/rcmb.2012-0050OC","article-title":"Matrix stiffness-induced myofibroblast differentiation is mediated by intrinsic mechanotransduction","volume":"47","author":"Huang","year":"2012","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.joca.2023.09.012_bib5","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nrm809","article-title":"Myofibroblasts and mechano-regulation of connective tissue remodelling","volume":"3","author":"Tomasek","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.joca.2023.09.012_bib6","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","article-title":"Matrix elasticity directs stem cell lineage specification","volume":"126","author":"Engler","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.joca.2023.09.012_bib7","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10137","article-title":"Role of YAP\/TAZ in mechanotransduction","volume":"474","author":"Dupont","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.joca.2023.09.012_bib8","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nmat4780","article-title":"MicroRNA-21 preserves the fibrotic mechanical memory of mesenchymal stem cells","volume":"16","author":"Li","year":"2017","journal-title":"Nat Mater"},{"issue":"16","key":"10.1016\/j.joca.2023.09.012_bib9","doi-asserted-by":"crossref","first-page":"3921","DOI":"10.1016\/j.biomaterials.2011.02.019","article-title":"The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-\u03b2","volume":"32","author":"Park","year":"2011","journal-title":"Biomaterials"},{"key":"10.1016\/j.joca.2023.09.012_bib10","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1093\/rheumatology\/kev228","article-title":"Unravelling osteoarthritis-related synovial fibrosis: a step closer to solving joint stiffness","volume":"54","author":"Remst","year":"2015","journal-title":"Rheumatology"},{"key":"10.1016\/j.joca.2023.09.012_bib11","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1152\/ajpcell.00041.2018","article-title":"cAMP attenuates TGF-\u2019s profibrotic responses in osteoarthritic synoviocytes: involvement of hyaluronan and PRG4","volume":"315","author":"Qadri","year":"2018","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.joca.2023.09.012_bib12","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/art.38266","article-title":"Gene expression analysis of murine and human osteoarthritis synovium reveals elevation of transforming growth factor \u03b2-responsive genes in osteoarthritis-related fibrosis","volume":"66","author":"Remst","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.joca.2023.09.012_bib13","doi-asserted-by":"crossref","first-page":"R151","DOI":"10.1186\/ar3887","article-title":"Hyaluronan injection in murine osteoarthritis prevents TGFbeta 1-induced synovial neovascularization and fibrosis and maintains articular cartilage integrity by a CD44-dependent mechanism","volume":"14","author":"Li","year":"2012","journal-title":"Arthritis Res Ther"},{"key":"10.1016\/j.joca.2023.09.012_bib14","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: a disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.joca.2023.09.012_bib15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/ar2099","article-title":"The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis","volume":"8","author":"Bondeson","year":"2006","journal-title":"Arthritis Res Ther"},{"key":"10.1016\/j.joca.2023.09.012_bib16","doi-asserted-by":"crossref","first-page":"40","DOI":"10.22203\/eCM.v013a04","article-title":"Bioregulation of lubricin expression by growth factors and cytokines","volume":"13","author":"Jones","year":"2007","journal-title":"Eur Cell Mater"},{"key":"10.1016\/j.joca.2023.09.012_bib17","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/art.22446","article-title":"Boundary lubrication of articular cartilage: role of synovial fluid constituents","volume":"56","author":"Schmidt","year":"2007","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.joca.2023.09.012_bib18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0143415","article-title":"Elastoviscous transitions of articular cartilage reveal a mechanism of synergy between lubricin and hyaluronic acid","volume":"10","author":"Bonnevie","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.joca.2023.09.012_bib19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jbiomech.2018.04.020","article-title":"Microscale frictional strains determine chondrocyte fate in loaded cartilage","volume":"74","author":"Bonnevie","year":"2018","journal-title":"J Biomech"},{"key":"10.1016\/j.joca.2023.09.012_bib20","doi-asserted-by":"crossref","first-page":"5852","DOI":"10.1073\/pnas.1219289110","article-title":"Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis","volume":"110","author":"Waller","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.joca.2023.09.012_bib21","first-page":"113","article-title":"Proteoglycan-4 regulates fibroblast to myofibroblast transition and expression of fibrotic genes in the synovium","volume":"22","author":"Qadri","year":"2020","journal-title":"Pharm Fac Artic Res"},{"key":"10.1016\/j.joca.2023.09.012_bib22","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.joca.2013.05.011","article-title":"The influence of synovial inflammation and hyperplasia on symptomatic outcomes up to 2 years post-operatively in patients undergoing partial meniscectomy","volume":"21","author":"Scanzello","year":"2013","journal-title":"Osteoarthr Cartil"},{"key":"10.1016\/j.joca.2023.09.012_bib23","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2005970","article-title":"CellProfiler 3.0: next-generation image processing for biology","volume":"16","author":"McQuin","year":"2018","journal-title":"PLoS Biol"},{"key":"10.1016\/j.joca.2023.09.012_bib24","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jbiomech.2017.06.011","article-title":"Fibroblast-like synoviocyte mechanosensitivity to fluid shear is modulated by interleukin-1\u03b1","volume":"60","author":"Estell","year":"2017","journal-title":"J Biomech"},{"key":"10.1016\/j.joca.2023.09.012_bib25","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1089\/ten.tea.2018.0142","article-title":"A functional tissue-engineered synovium model to study osteoarthritis progression and treatment","volume":"25","author":"Stefani","year":"2019","journal-title":"Tissue Eng Part A"},{"key":"10.1016\/j.joca.2023.09.012_bib26","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/s41551-019-0458-4","article-title":"Aberrant mechanosensing in injured intervertebral discs as a result of boundary-constraint disruption and residual-strain loss","volume":"3","author":"Bonnevie","year":"2019","journal-title":"Nat Biomed Eng"},{"key":"10.1016\/j.joca.2023.09.012_bib27","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-85276-5","article-title":"Cell morphology and mechanosensing can be decoupled in fibrous microenvironments and identified using artificial neural networks","volume":"11","author":"Bonnevie","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.joca.2023.09.012_bib28","doi-asserted-by":"crossref","DOI":"10.1038\/srep38852","article-title":"High fidelity visualization of cell-to-cell variation and temporal dynamics in nascent extracellular matrix formation","volume":"6","author":"McLeod","year":"2016","journal-title":"Sci Rep"},{"key":"10.1016\/j.joca.2023.09.012_bib29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/pharmaceutics12080706","article-title":"Fasudil loaded PLGA microspheres as potential intravitreal depot formulation for glaucoma therapy","volume":"12","author":"Mietzner","year":"2020","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.joca.2023.09.012_bib30","doi-asserted-by":"crossref","first-page":"L344","DOI":"10.1152\/ajplung.00300.2014","article-title":"Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis","volume":"308","author":"Liu","year":"2015","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.joca.2023.09.012_bib31","first-page":"1147","article-title":"Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis","volume":"293","author":"Georges","year":"2007","journal-title":"Am J Physiol"},{"key":"10.1016\/j.joca.2023.09.012_bib32","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s11926-009-0017-1","article-title":"Tissue stiffness, latent TGF-\u03b21 activation, and mechanical signal transduction: implications for the pathogenesis and treatment of fibrosis","volume":"11","author":"Hinz","year":"2009","journal-title":"Curr Rheumatol Rep"},{"key":"10.1016\/j.joca.2023.09.012_bib33","doi-asserted-by":"crossref","first-page":"pe13","DOI":"10.1126\/stke.110pe13","article-title":"Matrix elasticity, cytoskeletal tension, and TGF-\u03b2: the insoluble and soluble meet","volume":"1","author":"Wells","year":"2008","journal-title":"Sci Signal"},{"key":"10.1016\/j.joca.2023.09.012_bib34","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1002\/art.22974","article-title":"Association between friction and wear in diarthrodial joints lacking lubricin","volume":"56","author":"Jay","year":"2007","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.joca.2023.09.012_bib35","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1186\/s13075-015-0877-x","article-title":"The interaction of lubricin\/proteoglycan 4 (PRG4) with toll-like receptors 2 and 4: an anti-inflammatory role of PRG4 in synovial fluid","volume":"17","author":"Alquraini","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"10.1016\/j.joca.2023.09.012_bib36","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1161\/hc1002.105938","article-title":"Suppression of coronary artery spasm by the Rho-kinase inhibitor fasudil in patients with vasospastic angina","volume":"105","author":"Masumoto","year":"2002","journal-title":"Circulation"},{"key":"10.1016\/j.joca.2023.09.012_bib37","doi-asserted-by":"crossref","first-page":"438e","DOI":"10.1097\/PRS.0b013e31822b7352","article-title":"Wound contraction is attenuated by fasudil inhibition of Rho-associated kinase","volume":"128","author":"Bond","year":"2011","journal-title":"Plast Reconstr Surg"},{"key":"10.1016\/j.joca.2023.09.012_bib38","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jns.2005.06.003","article-title":"Effects of fasudil in acute ischemic stroke: results of a prospective placebo-controlled double-blind trial","volume":"238","author":"Shibuya","year":"2005","journal-title":"J Neurol Sci"},{"key":"10.1016\/j.joca.2023.09.012_bib39","first-page":"27","article-title":"Verteporfin inhibits YAP function through up-regulating 14-3-3\u03c3 sequestering YAP in the cytoplasm","volume":"6","author":"Wang","year":"2016","journal-title":"Am J Cancer Res"},{"key":"10.1016\/j.joca.2023.09.012_bib40","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.3389\/fphar.2018.01083","article-title":"Fasudil, a rho-kinase inhibitor, exerts cardioprotective function in animal models of myocardial ischemia\/reperfusion injury: a meta-analysis and review of preclinical evidence and possible mechanisms","volume":"9","author":"Huang","year":"2018","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.joca.2023.09.012_bib41","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1002\/jor.24340","article-title":"Cartilage wear particles induce an inflammatory response similar to cytokines in human fibroblast-like synoviocytes","volume":"37","author":"Estell","year":"2019","journal-title":"J Orthop Res"},{"key":"10.1016\/j.joca.2023.09.012_bib42","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/15496","article-title":"CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome","volume":"23","author":"Marcelino","year":"1999","journal-title":"Nat Genet"},{"key":"10.1016\/j.joca.2023.09.012_bib43","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1002\/art.39087","article-title":"Lubricin\/proteoglycan 4 binding to CD44 receptor: a mechanism of the suppression of proinflammatory cytokine-induced synoviocyte proliferation by lubricin","volume":"67","author":"Al-Sharif","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.joca.2023.09.012_bib44","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/nmat3889","article-title":"Mechanical memory and dosing influence stem cell fate","volume":"13","author":"Yang","year":"2014","journal-title":"Nat Mater"},{"key":"10.1016\/j.joca.2023.09.012_bib45","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1007\/s10439-020-02717-4","article-title":"Size-dependent effective diffusivity in healthy human and porcine joint synovium","volume":"49","author":"Guang","year":"2021","journal-title":"Ann Biomed Eng"},{"key":"10.1016\/j.joca.2023.09.012_bib46","doi-asserted-by":"crossref","first-page":"16725","DOI":"10.1038\/s41598-020-73270-2","article-title":"Synovial fluid lubricin increases in spontaneous canine cruciate ligament rupture","volume":"10","author":"Wang","year":"2020","journal-title":"Sci Rep"},{"key":"10.1016\/j.joca.2023.09.012_bib47","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1002\/art.23495","article-title":"Decreased lubricin concentrations and markers of joint inflammation in the synovial fluid of patients with anterior cruciate ligament injury","volume":"58","author":"Elsaid","year":"2008","journal-title":"Arthritis Rheum"}],"container-title":["Osteoarthritis and Cartilage"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1063458423009494?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1063458423009494?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T04:01:29Z","timestamp":1761019289000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1063458423009494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["S1063458423009494"],"URL":"https:\/\/doi.org\/10.1016\/j.joca.2023.09.012","relation":{},"ISSN":["1063-4584"],"issn-type":[{"value":"1063-4584","type":"print"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Modulating mechanobiology as a therapeutic target for synovial fibrosis to restore joint lubrication","name":"articletitle","label":"Article Title"},{"value":"Osteoarthritis and Cartilage","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.joca.2023.09.012","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.","name":"copyright","label":"Copyright"}]}}