{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:18:25Z","timestamp":1792271905078,"version":"4.4.0"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1944394"],"award-info":[{"award-number":["1944394"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2149946"],"award-info":[{"award-number":["2149946"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Synovial fluid is composed of hyaluronan and proteoglycan-4 (PRG4 or lubricin), which work synergistically to maintain joint lubrication. In diseases like osteoarthritis, hyaluronan and PRG4 concentrations can be altered, resulting in lowered synovial fluid viscosity, and pro-inflammatory cytokine concentrations within the synovial fluid increase. Synovial fibroblasts within the synovium are responsible for contributing to synovial fluid and can be targeted to improve endogenous production of hyaluronan and PRG4 and to alter the cytokine profile. We cyclically loaded SW982 synoviocytes to 0%, 5%, 10%, or 20% strain for three hours at 1 Hz. To assess the impact of substrate stiffness, we compared the 0% strain group to cells grown on tissue culture plastic. We measured the expression of hyaluronan turnover genes, hyaluronan localization within the cell layer, hyaluronan concentration, PRG4 concentration, and the cytokine profile within the media. Our results show that the addition of cyclic loading increased\n                    <jats:italic>HAS3<\/jats:italic>\n                    expression, but not in a magnitude-dependent response. Hyaluronidase expression was impacted by strain magnitude, which is exemplified by the decrease in hyaluronan concentration due to cyclic loading. We also show that PRG4 concentration is increased at 5% strain, while higher strain magnitude decreases overall PRG4 concentration. Finally, 10% and 20% strain show a distinct, more pro-inflammatory cytokine profile when compared to the unloaded group. Multivariate analysis showed distinct separation between certain strain groups in being able to predict strain group, hyaluronan concentration, and PRG4 concentration from gene expression or cytokine concentration data, highlighting the complexity of the system. Overall, this study shows that cyclic loading can be used tool to modulate the endogenous production of hyaluronan, PRG4, and cytokines from synovial fibroblasts.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0267921","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T13:26:57Z","timestamp":1672234017000},"page":"e0267921","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Endogenous production of hyaluronan, PRG4, and cytokines is sensitive to cyclic loading in synoviocytes"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2968-1746","authenticated-orcid":true,"given":"Meghana","family":"Pendyala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige S.","family":"Woods","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas K.","family":"Brubaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1924-0587","authenticated-orcid":true,"given":"Elizabeth A.","family":"Blaber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tannin A.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1508-1045","authenticated-orcid":true,"given":"Deva D.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,12,28]]},"reference":[{"issue":"3","key":"pone.0267921.ref001","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":"TA Schmidt","year":"2007","journal-title":"Arthritis Rheum"},{"key":"pone.0267921.ref002","doi-asserted-by":"crossref","first-page":"100","DOI":"10.2174\/1874312901105010100","article-title":"The normal synovium","volume":"5","author":"MD Smith","year":"2011","journal-title":"Open Rheumatol J"},{"issue":"10","key":"pone.0267921.ref003","doi-asserted-by":"crossref","first-page":"4377","DOI":"10.1021\/pr500587x","article-title":"A normative study of the synovial fluid proteome from healthy porcine knee joints","volume":"13","author":"T Bennike","year":"2014","journal-title":"Journal of proteome research"},{"key":"pone.0267921.ref004","doi-asserted-by":"crossref","first-page":"104117","DOI":"10.1016\/j.jmbbm.2020.104117","article-title":"The effect of albumin and gamma-globulin on synovial fluid lubrication: Implication for knee joint replacements","volume":"113","author":"D Necas","year":"2021","journal-title":"J Mech Behav Biomed Mater"},{"issue":"6","key":"pone.0267921.ref005","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1111\/eos.12082","article-title":"Synthesis of hyaluronan and superficial zone protein in synovial membrane cells modulated by fluid flow","volume":"121","author":"T Yanagida-Suekawa","year":"2013","journal-title":"Eur J Oral Sci"},{"issue":"1","key":"pone.0267921.ref006","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1006\/abbi.1994.1219","article-title":"A novel proteoglycan synthesized and secreted by chondrocytes of the superficial zone of articular cartilage","volume":"311","author":"BL Schumacher","year":"1994","journal-title":"Archives of biochemistry and biophysics"},{"key":"pone.0267921.ref007","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13075-016-0922-4","article-title":"Hyaluronan concentration and size distribution in human knee synovial fluid: variations with age and cartilage degeneration","volume":"18","author":"MM Temple-Wong","year":"2016","journal-title":"Arthritis Res Ther"},{"key":"pone.0267921.ref008","doi-asserted-by":"crossref","first-page":"622","DOI":"10.12688\/f1000research.6885.1","article-title":"Viscoelastic Properties of Hyaluronan in Physiological Conditions","volume":"4","author":"MK Cowman","year":"2015","journal-title":"F1000Res"},{"issue":"12","key":"pone.0267921.ref009","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1002\/art.34674","article-title":"Diminished cartilage-lubricating ability of human osteoarthritic synovial fluid deficient in proteoglycan 4: Restoration through proteoglycan 4 supplementation","volume":"64","author":"TE Ludwig","year":"2012","journal-title":"Arthritis Rheum"},{"issue":"2","key":"pone.0267921.ref010","first-page":"365","article-title":"Synovial membrane inflammation and cytokine production in patients with early osteoarthritis","volume":"24","author":"MD Smith","year":"1997","journal-title":"J Rheumatol"},{"issue":"1","key":"pone.0267921.ref011","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s13075-019-1923-x","article-title":"Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation","volume":"21","author":"CA Haraden","year":"2019","journal-title":"Arthritis Res Ther"},{"issue":"3","key":"pone.0267921.ref012","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.rdc.2019.04.011","article-title":"Intra-articular Hyaluronan Therapy for Symptomatic Knee Osteoarthritis.","volume":"45","author":"C Richardson","year":"2019","journal-title":"Rheum Dis Clin North Am"},{"issue":"4","key":"pone.0267921.ref013","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1080\/15216540214929","article-title":"Mammalian hyaluronan synthases","volume":"54","author":"N Itano","year":"2002","journal-title":"IUBMB Life"},{"issue":"4","key":"pone.0267921.ref014","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1002\/art.38315","article-title":"Gene expression pattern of cells from inflamed and normal areas of osteoarthritis synovial membrane","volume":"66","author":"C Lambert","year":"2014","journal-title":"Arthritis Rheumatol"},{"issue":"6","key":"pone.0267921.ref015","doi-asserted-by":"crossref","first-page":"R514","DOI":"10.1186\/ar1223","article-title":"Expression analysis of three isoforms of hyaluronan synthase and hyaluronidase in the synovium of knees in osteoarthritis and rheumatoid arthritis by quantitative real-time reverse transcriptase polymerase chain reaction","volume":"6","author":"M Yoshida","year":"2004","journal-title":"Arthritis Res Ther"},{"issue":"5","key":"pone.0267921.ref016","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1161\/01.RES.0000119169.87429.A0","article-title":"Induction of hyaluronic acid synthase 2 (HAS2) in human vascular smooth muscle cells by vasodilatory prostaglandins","volume":"94","author":"M Sussmann","year":"2004","journal-title":"Circ Res"},{"issue":"2","key":"pone.0267921.ref017","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.bbrc.2004.02.046","article-title":"Compound K induces expression of hyaluronan synthase 2 gene in transformed human keratinocytes and increases hyaluronan in hairless mouse skin","volume":"316","author":"S Kim","year":"2004","journal-title":"Biochemical and biophysical research communications"},{"issue":"4","key":"pone.0267921.ref018","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/03008207.2020.1751140","article-title":"Proteoglycan-4 and hyaluronan composition in synovial fluid and serum from clinical equine subjects: relationship to cartilage boundary lubrication and viscosity of synovial fluid","volume":"62","author":"A Matheson","year":"2021","journal-title":"Connect Tissue Res"},{"issue":"20","key":"pone.0267921.ref019","doi-asserted-by":"crossref","first-page":"18090","DOI":"10.1021\/acsami.9b01493","article-title":"Interactions between Lubricin and Hyaluronic Acid Synergistically Enhance Antiadhesive Properties","volume":"11","author":"H Ye","year":"2019","journal-title":"ACS Appl Mater Interfaces"},{"issue":"6","key":"pone.0267921.ref020","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3233\/BIR-14037","article-title":"Effects of concentration and structure on proteoglycan 4 rheology and interaction with hyaluronan","volume":"51","author":"TE Ludwig","year":"2014","journal-title":"Biorheology"},{"issue":"1","key":"pone.0267921.ref021","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.0105-2896.2009.00859.x","article-title":"Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis","volume":"233","author":"B Bartok","year":"2010","journal-title":"Immunol Rev"},{"issue":"1","key":"pone.0267921.ref022","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s12964-020-00678-8","article-title":"Reprogramming of synovial macrophage metabolism by synovial fibroblasts under inflammatory conditions","volume":"18","author":"N Saeki","year":"2020","journal-title":"Cell Commun Signal"},{"issue":"1\u20132","key":"pone.0267921.ref023","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jim.2013.08.007","article-title":"Chemokine and cytokine levels in osteoarthritis and rheumatoid arthritis synovial fluid","volume":"396","author":"U Hampel","year":"2013","journal-title":"J Immunol Methods"},{"issue":"7","key":"pone.0267921.ref024","doi-asserted-by":"crossref","first-page":"639","DOI":"10.3109\/1354750X.2016.1171907","article-title":"Plasma and synovial fluid inflammatory cytokine profiles in primary knee osteoarthritis","volume":"21","author":"T Mabey","year":"2016","journal-title":"Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals"},{"issue":"1","key":"pone.0267921.ref025","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12891-018-1955-4","article-title":"Serum and synovial fluid cytokine profiling in hip osteoarthritis: distinct from knee osteoarthritis and correlated with pain","volume":"19","author":"G Ren","year":"2018","journal-title":"BMC Musculoskelet Disord"},{"issue":"1","key":"pone.0267921.ref026","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrrheum.2010.196","article-title":"Role of proinflammatory cytokines in the pathophysiology of osteoarthritis.","volume":"7","author":"M Kapoor","year":"2011","journal-title":"Nat Rev Rheumatol"},{"issue":"7","key":"pone.0267921.ref027","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.jbiomech.2013.02.027","article-title":"Muscular loading of joints triggers cellular secretion of PRG4 into the joint fluid","volume":"46","author":"Z Abusara","year":"2013","journal-title":"J Biomech"},{"issue":"3","key":"pone.0267921.ref028","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3109\/03008209409061971","article-title":"Proteoglycan and collagen alterations in canine knee articular cartilage following 20 km daily running exercise for 15 weeks","volume":"30","author":"AM Saamamen","year":"1994","journal-title":"Connect Tissue Res"},{"issue":"9","key":"pone.0267921.ref029","first-page":"1586","article-title":"Coordinated regulation of hyaluronan and aggrecan content in the articular cartilage of immobilized and exercised dogs","volume":"23","author":"J Haapala","year":"1996","journal-title":"J Rheumatol"},{"issue":"5","key":"pone.0267921.ref030","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.rehab.2019.04.006","article-title":"Efficacy and potential determinants of exercise therapy in knee and hip osteoarthritis: A systematic review and meta-analysis","volume":"62","author":"SL Goh","year":"2019","journal-title":"Ann Phys Rehabil Med"},{"issue":"1","key":"pone.0267921.ref031","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s10616-013-9669-9","article-title":"Hyaluronic acid secretion by synoviocytes alters under cyclic compressive load in contracted collagen gels","volume":"67","author":"K Uehara","year":"2015","journal-title":"Cytotechnology"},{"issue":"9","key":"pone.0267921.ref032","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1302\/2046-3758.39.2000287","article-title":"Cyclic compressive loading on 3D tissue of human synovial fibroblasts upregulates prostaglandin E2 via COX-2 production without IL-1beta and TNF-alpha","volume":"3","author":"K Shimomura","year":"2014","journal-title":"Bone Joint Res"},{"issue":"6","key":"pone.0267921.ref033","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1089\/ten.2006.12.1527","article-title":"Effects of dynamic compressive load on collagen-based scaffolds seeded with fibroblast-like synoviocytes","volume":"12","author":"DB Fox","year":"2006","journal-title":"Tissue Eng"},{"issue":"3","key":"pone.0267921.ref034","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20030585","article-title":"Impact of Mechanical Load on the Expression Profile of Synovial Fibroblasts from Patients with and without Osteoarthritis","volume":"20","author":"A Schroder","year":"2019","journal-title":"International journal of molecular sciences"},{"issue":"1","key":"pone.0267921.ref035","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3892\/mmr.2012.1168","article-title":"Effects of exercise therapy on knee joint function and synovial fluid cytokine levels in patients with knee osteoarthritis","volume":"7","author":"SL Zhang","year":"2013","journal-title":"Mol Med Rep"},{"issue":"1","key":"pone.0267921.ref036","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1186\/s13104-020-05249-1","article-title":"Mechanical stimulation of human dermal fibroblasts regulates pro-inflammatory cytokines: potential insight into soft tissue manual therapies","volume":"13","author":"A Anloague","year":"2020","journal-title":"BMC research notes"},{"issue":"8","key":"pone.0267921.ref037","doi-asserted-by":"crossref","first-page":"e0182369","DOI":"10.1371\/journal.pone.0182369","article-title":"Variable stretch reduces the pro-inflammatory response of alveolar epithelial cells.","volume":"12","author":"I Rentzsch","year":"2017","journal-title":"PLoS One"},{"issue":"11","key":"pone.0267921.ref038","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21113874","article-title":"Early OA Stage Like Response Occurs after Dynamic Stretching of Human Synovial Fibroblasts","volume":"21","author":"U Nazet","year":"2020","journal-title":"International journal of molecular sciences"},{"issue":"3","key":"pone.0267921.ref039","doi-asserted-by":"crossref","first-page":"190","DOI":"10.3109\/03008207.2010.508853","article-title":"Cyclic mechanical stretch downregulates IL-1beta-induced COX-2 expression and PGE(2) production in rheumatoid arthritis fibroblast-like synoviocytes","volume":"52","author":"P Wang","year":"2011","journal-title":"Connect Tissue Res"},{"issue":"8","key":"pone.0267921.ref040","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.matbio.2005.08.006","article-title":"Hyaluronan secretion by synoviocytes is mechanosensitive","volume":"24","author":"TS Momberger","year":"2005","journal-title":"Matrix Biol"},{"key":"pone.0267921.ref041","doi-asserted-by":"crossref","first-page":"109392","DOI":"10.1016\/j.cellsig.2019.109392","article-title":"TGF-beta1 promotes hyaluronan synthesis by upregulating hyaluronan synthase 2 expression in human granulosa-lutein cells","volume":"63","author":"F Wang","year":"2019","journal-title":"Cell Signal"},{"issue":"5","key":"pone.0267921.ref042","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1007\/s10753-019-01043-9","article-title":"Role of Hyaluronan in Inflammatory Effects on Human Articular Chondrocytes","volume":"42","author":"MK Cowman","year":"2019","journal-title":"Inflammation"},{"issue":"3","key":"pone.0267921.ref043","first-page":"252","article-title":"Viewing hyaluronan: imaging contributes to imagining new roles for this amazing matrix polymer. The journal of histochemistry and cytochemistry: official journal of the","volume":"59","author":"CA de la Motte","year":"2011","journal-title":"Histochemistry Society"},{"key":"pone.0267921.ref044","article-title":"Image Processing with ImageJ.","author":"MD Abr\u00e0moff","year":"2004","journal-title":"Biophotonics International"},{"issue":"7","key":"pone.0267921.ref045","first-page":"676","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat MethodsPubMed Central PMCID"},{"key":"pone.0267921.ref046","first-page":"100916","article-title":"A simple method for quantitating confocal fluorescent images","volume":"25","author":"MH Shihan","year":"2021","journal-title":"Biochem Biophys Rep"},{"key":"pone.0267921.ref047","doi-asserted-by":"crossref","first-page":"787193","DOI":"10.3389\/fphar.2021.787193","article-title":"Proteomics Analysis of Tears and Saliva From Sjogren\u2019s Syndrome Patients.","volume":"12","author":"N Das","year":"2021","journal-title":"Front Pharmacol"},{"key":"pone.0267921.ref048","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.exer.2014.06.015","article-title":"Characterization of full-length recombinant human Proteoglycan 4 as an ocular surface boundary lubricant","volume":"127","author":"ML Samsom","year":"2014","journal-title":"Experimental eye research"},{"key":"pone.0267921.ref049","author":"R Development Core Team","year":"2010"},{"key":"pone.0267921.ref050","author":"RStudio Team","year":"2020"},{"issue":"11","key":"pone.0267921.ref051","doi-asserted-by":"crossref","first-page":"e1005752","DOI":"10.1371\/journal.pcbi.1005752","article-title":"mixOmics: An R package for \u2019omics feature selection and multiple data integration","volume":"13","author":"F Rohart","year":"2017","journal-title":"PLoS Comput Biol"},{"issue":"2","key":"pone.0267921.ref052","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1080\/03008207.2018.1470167","article-title":"Conditioned media from human osteoarthritic synovium induces inflammation in a synoviocyte cell line","volume":"60","author":"E Belluzzi","year":"2019","journal-title":"Connect Tissue Res"},{"issue":"8","key":"pone.0267921.ref053","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1002\/term.2704","article-title":"Cultures of a human synovial cell line to evaluate platelet-rich plasma and hyaluronic acid effects","volume":"12","author":"E Olivotto","year":"2018","journal-title":"J Tissue Eng Regen Med"},{"issue":"35","key":"pone.0267921.ref054","doi-asserted-by":"crossref","first-page":"22884","DOI":"10.1021\/acsami.6b07097","article-title":"Softening Substrates Promote Chondrocytes Phenotype via RhoA\/ROCK Pathway.","volume":"8","author":"T Zhang","year":"2016","journal-title":"ACS Appl Mater Interfaces"},{"issue":"11","key":"pone.0267921.ref055","doi-asserted-by":"crossref","first-page":"e27170","DOI":"10.1371\/journal.pone.0027170","article-title":"Extracellular matrix ligand and stiffness modulate immature nucleus pulposus cell-cell interactions","volume":"6","author":"CL Gilchrist","year":"2011","journal-title":"PLoS One"},{"issue":"11","key":"pone.0267921.ref056","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1002\/jor.23212","article-title":"First in vivo detection and characterization of hyaluronan-coated extracellular vesicles in human synovial fluid","volume":"34","author":"AM Mustonen","year":"2016","journal-title":"J Orthop Res"},{"key":"pone.0267921.ref057","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.semcancer.2019.07.002","article-title":"Intracellular hyaluronan: Importance for cellular functions","volume":"62","author":"SS Skandalis","year":"2020","journal-title":"Semin Cancer Biol"},{"issue":"1\u20132","key":"pone.0267921.ref058","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bbagen.2004.02.013","article-title":"Intracellular hyaluronan: a new frontier for inflammation?","volume":"1673","author":"VC Hascall","year":"2004","journal-title":"Biochim Biophys Acta"},{"issue":"6","key":"pone.0267921.ref059","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1002\/art.21831","article-title":"Dynamic shear stimulation of bovine cartilage biosynthesis of proteoglycan 4","volume":"54","author":"GE Nugent","year":"2006","journal-title":"Arthritis Rheum"},{"issue":"8","key":"pone.0267921.ref060","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.joca.2012.04.019","article-title":"Dynamic compression improves biosynthesis of human zonal chondrocytes from osteoarthritis patients","volume":"20","author":"JE Jeon","year":"2012","journal-title":"Osteoarthritis Cartilage"},{"issue":"3","key":"pone.0267921.ref061","first-page":"191","article-title":"Static and dynamic compression regulate cartilage metabolism of PRoteoGlycan 4 (PRG4)","volume":"43","author":"GE Nugent","year":"2006","journal-title":"Biorheology"},{"key":"pone.0267921.ref062","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1186\/s12891-015-0842-5","article-title":"Cartilage boundary lubrication synergism is mediated by hyaluronan concentration and PRG4 concentration and structure","volume":"16","author":"TE Ludwig","year":"2015","journal-title":"BMC Musculoskelet Disord"},{"issue":"3","key":"pone.0267921.ref063","doi-asserted-by":"crossref","first-page":"170","DOI":"10.2174\/1573397113666170427125918","article-title":"Synovial Fluid and Serum Concentrations of Inflammatory Markers in Rheumatoid Arthritis, Psoriatic Arthritis and Osteoarthitis: A Systematic Review","volume":"13","author":"E Altobelli","year":"2017","journal-title":"Curr Rheumatol Rev"},{"issue":"2","key":"pone.0267921.ref064","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3233\/THC-191811","article-title":"Elevated synovial fluid IL-33 and IL-6 levels and cartilage degeneration in stage III osteonecrosis of the femoral head","volume":"28","author":"YH Gao","year":"2020","journal-title":"Technology and health care: official journal of the European Society for Engineering and Medicine"},{"key":"pone.0267921.ref065","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.intimp.2018.09.011","article-title":"Enhanced neutrophil autophagy and increased concentrations of IL-6, IL-8, IL-10 and MCP-1 in rheumatoid arthritis","volume":"65","author":"Q An","year":"2018","journal-title":"Int Immunopharmacol"},{"key":"pone.0267921.ref066","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cyto.2015.12.020","article-title":"IL-9, a local growth factor for synovial T cells in inflammatory arthritis","volume":"79","author":"S Kundu-Raychaudhuri","year":"2016","journal-title":"Cytokine"},{"issue":"3","key":"pone.0267921.ref067","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1006\/clin.1995.1157","article-title":"Macrophage inflammatory protein-1 beta: a C-C chemokine in osteoarthritis","volume":"77","author":"AE Koch","year":"1995","journal-title":"Clin Immunol Immunopathol"},{"issue":"9","key":"pone.0267921.ref068","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1111\/joor.13041","article-title":"Increased chemokine RANTES in synovial fluid and its role in early-stage degenerative temporomandibular joint disease","volume":"47","author":"SY Feng","year":"2020","journal-title":"J Oral Rehabil"},{"issue":"1","key":"pone.0267921.ref069","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cyto.2010.03.015","article-title":"Modulation of the response of rheumatoid arthritis synovial fibroblasts to proinflammatory stimulants with cyclic tensile strain","volume":"51","author":"RA Bader","year":"2010","journal-title":"Cytokine"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0267921","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T13:27:53Z","timestamp":1672234073000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0267921"}},"subtitle":[],"editor":[{"given":"Andre","family":"van Wijnen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,12,28]]},"references-count":69,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0267921","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.04.20.488903","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,28]]}}}