{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:40:43Z","timestamp":1771468843074,"version":"3.50.1"},"reference-count":78,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Orthodontic Society DGKFO","award":["Kirschneck 2020"],"award-info":[{"award-number":["Kirschneck 2020"]}]},{"name":"DFG grant GR1301\/19-1","award":["research consortium FOR2407\/1 S. Gr\u00e4ssel"],"award-info":[{"award-number":["research consortium FOR2407\/1 S. Gr\u00e4ssel"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Genetic predisposition, traumatic events, or excessive mechanical exposure provoke arthritic changes in the temporomandibular joint (TMJ). We analysed the impact of mechanical stress that might be involved in the development and progression of TMJ osteoarthritis (OA) on murine synovial fibroblasts (SFs) of temporomandibular origin. SFs were subjected to different protocols of mechanical stress, either to a high-frequency tensile strain for 4 h or to a tensile strain of varying magnitude for 48 h. The TMJ OA induction was evaluated based on the gene and protein secretion of inflammatory factors (Icam-1, Cxcl-1, Cxcl-2, Il-1\u00df, Il-1ra, Il-6, Ptgs-2, PG-E2), subchondral bone remodelling (Rankl, Opg), and extracellular matrix components (Col1a2, Has-1, collagen and hyaluronic acid deposition) using RT-qPCR, ELISA, and HPLC. A short high-frequency tensile strain had only minor effects on inflammatory factors and no effects on the subchondral bone remodelling induction or matrix constituent production. A prolonged tensile strain of moderate and advanced magnitude increased the expression of inflammatory factors. An advanced tensile strain enhanced the Ptgs-2 and PG-E2 expression, while the expression of further inflammatory factors were decreased. The tensile strain protocols had no effects on the RANKL\/OPG expression, while the advanced tensile strain significantly reduced the deposition of matrix constituent contents of collagen and hyaluronic acid. The data indicates that the application of prolonged advanced mechanical stress on SFs promote PG-E2 protein secretion, while the deposition of extracellular matrix components is decreased.<\/jats:p>","DOI":"10.3390\/cells10020298","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T11:40:48Z","timestamp":1612179648000},"page":"298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mechanical Stress Induce PG-E2 in Murine Synovial Fibroblasts Originating from the Temporomandibular Joint"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5090-2713","authenticated-orcid":false,"given":"Ute","family":"Nazet","sequence":"first","affiliation":[{"name":"Department of Orthodontics, University Medical Centre of Regensburg, D-93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Feulner","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Medical Centre of Regensburg, D-93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9791-2070","authenticated-orcid":false,"given":"Dominique","family":"Muschter","sequence":"additional","affiliation":[{"name":"Centre for Medical Biotechnology, Department of Orthopaedic Surgery, Experimental Orthopaedics, University of Regensburg, D-93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Neubert","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, D-93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentin","family":"Schatz","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, D-93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2549-8285","authenticated-orcid":false,"given":"Susanne","family":"Gr\u00e4ssel","sequence":"additional","affiliation":[{"name":"Centre for Medical Biotechnology, Department of Orthopaedic Surgery, Experimental Orthopaedics, University of Regensburg, D-93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Jantsch","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, D-93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Proff","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Medical Centre of Regensburg, D-93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6010-9831","authenticated-orcid":false,"given":"Agnes","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Medical Centre of Regensburg, D-93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9473-8724","authenticated-orcid":false,"given":"Christian","family":"Kirschneck","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Medical Centre of Regensburg, D-93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1007\/s11914-018-0447-7","article-title":"Part I: Development and Physiology of the Temporomandibular Joint","volume":"16","author":"Stocum","year":"2018","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1601-0825.2010.01782.x","article-title":"In vivo morphometric analysis of inflammatory condylar changes in rat temporomandibular joint","volume":"17","author":"Kuroki","year":"2011","journal-title":"Oral Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1177\/0022034515574770","article-title":"Current understanding of pathogenesis and treatment of TMJ osteoarthritis","volume":"94","author":"Wang","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bleuel, J., Zaucke, F., Br\u00fcggemann, G.-P., and Niehoff, A. (2015). Effects of cyclic tensile strain on chondrocyte metabolism: A systematic review. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119816"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.semcdb.2016.05.009","article-title":"The joint synovium: A critical determinant of articular cartilage fate in inflammatory joint diseases","volume":"62","author":"Bhattaram","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1113\/JP270209","article-title":"Cellular electrophysiological principles that modulate secretion from synovial fibroblasts","volume":"595","author":"Clark","year":"2017","journal-title":"J. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/wsbm.157","article-title":"A systems biology approach to synovial joint lubrication in health, injury, and disease","volume":"4","author":"Hui","year":"2012","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1002\/art.30294","article-title":"RNA sensors in human osteoarthritis and rheumatoid arthritis synovial fibroblasts: Immune regulation by vasoactive intestinal peptide","volume":"63","author":"Juarranz","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1002\/art.24140","article-title":"Overexpression of toll-like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: Toll-like receptor expression in early and longstanding arthritis","volume":"58","author":"Ospelt","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/cei.12979","article-title":"The role of stromal cells in inflammatory bone loss","volume":"189","author":"Wehmeyer","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2042-6410-4-4","article-title":"Addressing the gaps: Sex differences in osteoarthritis of the knee","volume":"4","author":"Boyan","year":"2013","journal-title":"Biol. Sex Differ."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.joca.2013.02.653","article-title":"Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury","volume":"21","author":"Boyce","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_13","first-page":"487","article-title":"Articular cartilage: Degeneration and osteoarthritis, repair, regeneration, and transplantation","volume":"47","author":"Buckwalter","year":"1998","journal-title":"Instr. Course Lect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11420-011-9251-y","article-title":"The role of mechanical forces in the initiation and progression of osteoarthritis","volume":"8","author":"Buckwalter","year":"2012","journal-title":"HSS J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s13191-013-0321-3","article-title":"Temporomandibular joint osteoarthritis: Diagnosis and long-term conservative management: A topic review","volume":"14","author":"Kalladka","year":"2014","journal-title":"J. Indian Prosthodont. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.archoralbio.2013.02.008","article-title":"Osteoarthritis in temporomandibular joint of Col2a1 mutant mice","volume":"58","author":"Ricks","year":"2013","journal-title":"Arch. Oral Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.3899\/jrheum.111441","article-title":"Risk factors for temporomandibular joint arthritis in children with juvenile idiopathic arthritis","volume":"39","author":"Stoll","year":"2012","journal-title":"J. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.joca.2015.09.013","article-title":"Synovitis and the risk of knee osteoarthritis: The MOST Study","volume":"24","author":"Felson","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13075-017-1229-9","article-title":"Synovitis in osteoarthritis: Current understanding with therapeutic implications","volume":"19","author":"Mathiessen","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1136\/ard.2011.150243","article-title":"Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: The MOST study","volume":"70","author":"Roemer","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hou, C.-H., Tang, C.-H., Hsu, C.-J., Hou, S.-M., and Liu, J.-F. (2013). CCN4 induces IL-6 production through \u03b1v\u03b25 receptor, PI3K, Akt, and NF-\u03baB singling pathway in human synovial fibroblasts. Arthritis Res. Ther., 15.","DOI":"10.1186\/ar4151"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hou, S.-M., Hou, C.-H., and Liu, J.-F. (2017). CX3CL1 promotes MMP-3 production via the CX3CR1, c-Raf, MEK, ERK, and NF-\u03baB signaling pathway in osteoarthritis synovial fibroblasts. Arthritis Res. Ther., 19.","DOI":"10.1186\/s13075-017-1487-6"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.clim.2004.12.009","article-title":"The fibroblast-like synovial cell in rheumatoid arthritis: A key player in inflammation and joint destruction","volume":"115","author":"Mor","year":"2005","journal-title":"Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.bone.2012.02.012","article-title":"The role of synovitis in osteoarthritis pathogenesis","volume":"51","author":"Scanzello","year":"2012","journal-title":"Bone"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.bone.2010.09.010","article-title":"Subchondral bone loss following orthodontically induced cartilage degradation in the mandibular condyles of rats","volume":"48","author":"Jiao","year":"2011","journal-title":"Bone"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1177\/0022034511421930","article-title":"Role of subchondral bone during early-stage experimental TMJ osteoarthritis","volume":"90","author":"Embree","year":"2011","journal-title":"J. Dent. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.2106\/00004623-199607000-00016","article-title":"Cellular biology of bone-resorbing cells","volume":"78","author":"Athanasou","year":"1996","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/BF02411252","article-title":"Bone acid phosphatase: Tartrate-resistant acid phosphatase as a marker of osteoclast function","volume":"34","author":"Minkin","year":"1982","journal-title":"Calcif. Tissue Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1615\/CritRevEukarGeneExpr.v19.i1.30","article-title":"Action of RANKL and OPG for osteoclastogenesis","volume":"19","author":"Kobayashi","year":"2009","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jaut.2012.06.001","article-title":"Rheumatoid and pyrophosphate arthritis synovial fibroblasts induce osteoclastogenesis independently of RANKL, TNF and IL-6","volume":"39","author":"Dickerson","year":"2012","journal-title":"J. Autoimmun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/1529-0131(200002)43:2<259::AID-ANR4>3.0.CO;2-W","article-title":"Involvement of receptor activator of nuclear factor kappaB ligand\/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis","volume":"43","author":"Takayanagi","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/art.24143","article-title":"Modulation of lubricin biosynthesis and tissue surface properties following cartilage mechanical injury","volume":"60","author":"Jones","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s00418-004-0697-6","article-title":"Expression of collagen type I and type II in consecutive stages of human osteoarthritis","volume":"122","author":"Miosge","year":"2004","journal-title":"Histochem. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Siiskonen, H., Oikari, S., Pasonen-Sepp\u00e4nen, S., and Rilla, K. (2015). Hyaluronan synthase 1: A mysterious enzyme with unexpected functions. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00043"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhong, D., Zhang, M., Yu, J., and Luo, Z.-P. (2018). Local Tensile Stress in the Development of Posttraumatic Osteoarthritis. Biomed Res. Int., 2018.","DOI":"10.1155\/2018\/4210353"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Armaka, M., Gkretsi, V., Kontoyiannis, D., and Kollias, G. (2009). A standardized protocol for the isolation and culture of normal and arthritogenic murine synovial fibroblasts. Nat. Protoc., PREPRINT (Version 1).","DOI":"10.1038\/nprot.2009.102"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1002\/art.40128","article-title":"Genomic Responses of Mouse Synovial Fibroblasts During Tumor Necrosis Factor-Driven Arthritogenesis Greatly Mimic Those in Human Rheumatoid Arthritis","volume":"69","author":"Ntougkos","year":"2017","journal-title":"Arthritis Rheum."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Muschter, D., Beiderbeck, A.-S., Sp\u00e4th, T., Kirschneck, C., Schr\u00f6der, A., and Gr\u00e4ssel, S. (2019). Sensory Neuropeptides and their Receptors Participate in Mechano-Regulation of Murine Macrophages. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030503"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cellsig.2018.12.010","article-title":"Mechanical exposure and diacerein treatment modulates integrin-FAK-MAPKs mechanotransduction in human osteoarthritis chondrocytes","volume":"56","author":"Lohberger","year":"2019","journal-title":"Cell. Signal."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Nazet, U., Schr\u00f6der, A., Gr\u00e4ssel, S., Muschter, D., Proff, P., and Kirschneck, C. (2019). Housekeeping gene validation for RT-qPCR studies on synovial fibroblasts derived from healthy and osteoarthritic patients with focus on mechanical loading. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0225790"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/MOH.0000000000000103","article-title":"The physiological roles of ICAM-1 and ICAM-2 in neutrophil migration into tissues","volume":"22","author":"Lyck","year":"2015","journal-title":"Curr. Opin. Hematol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3109\/10428199609051611","article-title":"New insights into the regulation of ICAM-1 gene expression","volume":"20","author":"Ohh","year":"1996","journal-title":"Leuk. Lymphoma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.aanat.2007.02.008","article-title":"Prevalence and clinical signs of degenerative temporomandibular joint changes validated by magnetic resonance imaging in a non-patient group","volume":"189","author":"Bernhardt","year":"2007","journal-title":"Ann. Anat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1007\/s00103-012-1483-6","article-title":"Study of Health in Pomerania (SHIP). Konzept, Kohortendesign und ausgew\u00e4hlte Ergebnisse","volume":"55","year":"2012","journal-title":"Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1259\/dmfr\/16270943","article-title":"Prevalence of clinical and radiographic signs of osteoarthrosis of the temporomandibular joint in an older persons community","volume":"39","author":"Schmitter","year":"2010","journal-title":"Dentomaxillofac. Radiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4103\/2321-1407.148014","article-title":"Current status of temporomandibular joint disorders and the therapeutic system derived from a series of biomechanical, histological, and biochemical studies","volume":"5","author":"Tanne","year":"2015","journal-title":"APOS Trends Orthod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1016\/j.pain.2011.09.005","article-title":"Cytokine biomarkers and chronic pain: Association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness","volume":"152","author":"Slade","year":"2011","journal-title":"Pain"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.joms.2009.10.027","article-title":"Increased levels of soluble cytokine receptors in the synovial fluid of temporomandibular joint disorders in relation to joint effusion on magnetic resonance images","volume":"68","author":"Kaneyama","year":"2010","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e337","DOI":"10.1016\/j.jcms.2012.02.002","article-title":"Analysis of the cytokine profiles of the synovial fluid in a normal temporomandibular joint: Preliminary study","volume":"40","author":"Kim","year":"2012","journal-title":"J. Craniomaxillofac. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1177\/0022034512441946","article-title":"Sustained inflammation induces degeneration of the temporomandibular joint","volume":"91","author":"Wang","year":"2012","journal-title":"J. Dent. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/art.27204","article-title":"Nonsteroidal antiinflammatory drugs and prostaglandin E(2) modulate the synthesis of osteoprotegerin and RANKL in the cartilage of patients with severe knee osteoarthritis","volume":"62","author":"Tardio","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1002\/art.24258","article-title":"Prostaglandin E2 and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis","volume":"60","author":"Li","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1177\/0022034514560588","article-title":"Effects of enzymatic degradation after loading in temporomandibular joint","volume":"94","author":"Su","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000086195","article-title":"Reduction of temporomandibular joint pain after treatment with a combination of methotrexate and infliximab is associated with changes in synovial fluid and plasma cytokines in rheumatoid arthritis","volume":"180","author":"Kopp","year":"2005","journal-title":"Cells Tissues Organs"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1172\/JCI114622","article-title":"Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist","volume":"85","author":"Arend","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1476-5381.1994.tb16174.x","article-title":"The involvement of bradykinin B1 and B2 receptor mechanisms in cytokine-induced mechanical hyperalgesia in the rat","volume":"113","author":"Davis","year":"1994","journal-title":"Br. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yang, Y., Zhou, X., Li, Y., Chen, A., Liang, W., Liang, G., Huang, B., Li, Q., and Jin, D. (2019). CXCL2 attenuates osteoblast differentiation by inhibiting the ERK1\/2 signaling pathway. J. Cell Sci., 132.","DOI":"10.1242\/jcs.230490"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1182\/blood-2013-02-486217","article-title":"Mast cell and macrophage chemokines CXCL1\/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation","volume":"121","author":"Dudeck","year":"2013","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.archoralbio.2008.04.004","article-title":"Expression of proinflammatory cytokines in osteoarthritis of the temporomandibular joint","volume":"53","author":"Vernal","year":"2008","journal-title":"Arch. Oral Biol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Hou, S.-M., Chen, P.-C., Lin, C.-M., Fang, M.-L., Chi, M.-C., and Liu, J.-F. (2020). CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK, and AP-1 pathway. Arthritis Res. Ther., 22.","DOI":"10.1186\/s13075-020-02331-8"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1002\/art.33445","article-title":"Regulation of subchondral bone osteoblast metabolism by cyclic compression","volume":"64","author":"Sanchez","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.joca.2008.05.021","article-title":"Altered functional loading causes differential effects in the subchondral bone and condylar cartilage in the temporomandibular joint from young mice","volume":"17","author":"Chen","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1111\/joor.12649","article-title":"Th1\/Th17\/Th22 immune response and their association with joint pain, imagenological bone loss, RANKL expression and osteoclast activity in temporomandibular joint osteoarthritis: A preliminary report","volume":"45","author":"Monasterio","year":"2018","journal-title":"J. Oral Rehabil."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1113\/jphysiol.1995.sp020722","article-title":"Effect of intra-articular hyaluronan on pressure-flow relation across synovium in anaesthetized rabbits","volume":"485","author":"McDonald","year":"1995","journal-title":"J. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1113\/jphysiol.1953.sp004842","article-title":"The physiological function of hyaluronic acid in synovial fluid; viscous, elastic and lubricant properties","volume":"119","author":"Ogston","year":"1953","journal-title":"J. Physiol."},{"key":"ref_66","first-page":"721","article-title":"The intrinsic viscosity of synovial fluid hyaluronic acid","volume":"48","author":"Bollet","year":"1956","journal-title":"J. Lab. Clin. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/clinchem\/5.5.465","article-title":"Concentration of hyaluronic acid in synovial fluid","volume":"5","author":"Decker","year":"1959","journal-title":"Clin. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3233\/BIR-1993-305-612","article-title":"Comparisons of the oscillatory shear viscoelasticity and composition of pathological synovial fluids","volume":"30","author":"Gomez","year":"1993","journal-title":"Biorheology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s00441-012-1504-7","article-title":"Lentiviral-mediated over-expression of hyaluronan synthase-1 (HAS-1) decreases the cellular inflammatory response and results in regenerative wound repair","volume":"351","author":"Caskey","year":"2013","journal-title":"Cell Tissue Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8753","DOI":"10.1074\/jbc.M303945200","article-title":"Differential effect of transforming growth factor beta (TGF-beta) on the genes encoding hyaluronan synthases and utilization of the p38 MAPK pathway in TGF-beta-induced hyaluronan synthase 1 activation","volume":"279","author":"Stuhlmeier","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1111\/j.0022-202X.2004.22332.x","article-title":"Differential regulation by IL-1beta and EGF of expression of three different hyaluronan synthases in oral mucosal epithelial cells and fibroblasts and dermal fibroblasts: Quantitative analysis using real-time RT-PCR","volume":"122","author":"Yamada","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1111\/j.1742-4658.2011.08070.x","article-title":"Transcriptional and post-translational regulation of hyaluronan synthesis","volume":"278","author":"Tammi","year":"2011","journal-title":"FEBS J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.matbio.2010.12.003","article-title":"Hyaluronan deposition and correlation with inflammation in a murine ovalbumin model of asthma","volume":"30","author":"Cheng","year":"2011","journal-title":"Matrix Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1002\/art.21038","article-title":"Association of articular cartilage degradation and loss of boundary-lubricating ability of synovial fluid following injury and inflammatory arthritis","volume":"52","author":"Elsaid","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/art.21638","article-title":"Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage","volume":"54","author":"Sato","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Sanchez, A., Blanco, M., Correa, B., Perez-Martin, R.I., and Sotelo, C.G. (2018). Effect of Fish Collagen Hydrolysates on Type I Collagen mRNA Levels of Human Dermal Fibroblast Culture. Mar. Drugs, 16.","DOI":"10.3390\/md16050144"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.aanat.2011.10.004","article-title":"Functional states of mandibular movements and synovial pumps of the temporomandibular joint. Is it possible to provide a biomechanically correct replacement for the TMJ?","volume":"194","author":"Hahn","year":"2012","journal-title":"Ann. Anat."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/j.1365-2842.2012.02307.x","article-title":"Synovial fluid dynamics with small disc perforation in temporomandibular joint","volume":"39","author":"Xu","year":"2012","journal-title":"J. Oral Rehabil."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/2\/298\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:18:23Z","timestamp":1760159903000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/2\/298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,1]]},"references-count":78,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["cells10020298"],"URL":"https:\/\/doi.org\/10.3390\/cells10020298","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,1]]}}}