{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:05:00Z","timestamp":1780635900491,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lubricin, also known as proteoglycan 4 (PRG4), is a key glycoprotein involved in boundary lubrication and maintenance of joint homeostasis in the temporomandibular joint (TMJ). However, the clinical evidence regarding synovial fluid (SF) lubricin levels remains limited and fragmented. This scoping review aimed to map and synthesize the available clinical evidence on lubricin levels in patients with temporomandibular disorders (TMDs) and their relationship to clinical outcomes, particularly pain and mandibular mobility. Searches were conducted in PubMed, Scopus, ACM, BASE, Cochrane, ClinicalTrials.gov, and Google Scholar. After duplicate removal and screening, two studies were included in the final synthesis. Preliminary findings from these studies suggest that (SF) lubricin levels may be lower in more advanced TMJ pathology, particularly in degenerative disease. Earlier stages of internal derangement showed lubricin concentrations closer to those observed in healthy controls, whereas advanced internal derangement and osteoarthritic disease were potentially associated with lower levels. One study also reported an inverse correlation between lubricin concentration and pain intensity, while the other demonstrated impaired boundary lubrication in TMD groups. Overall, the available clinical evidence is very limited and insufficient to establish PRG4 as a validated biomarker but suggests a possible association between reduced SF lubricin levels and more advanced TMJ disease. Further well-designed clinical studies are required to confirm these observations and clarify their diagnostic and therapeutic relevance.<\/jats:p>","DOI":"10.3390\/ijms27115035","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:38:42Z","timestamp":1780411122000},"page":"5035","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lubricin Levels in Temporomandibular Joint Disorders: A Scoping Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7698-9254","authenticated-orcid":false,"given":"Pawe\u0142","family":"Sikora","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Medical University of Lublin, Al. Rac\u0142awickie 1, 20-059 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6199-4753","authenticated-orcid":false,"given":"Maciej","family":"Ch\u0119ci\u0144ski","sequence":"additional","affiliation":[{"name":"National Medical Institute of the Ministry of the Interior and Administration, Wo\u0142oska 137, 02-507 Warsaw, Poland"},{"name":"Department of Maxillofacial Surgery, Hospital of the Ministry of the Interior and Administration, Wojska Polskiego 51, 25-375 Kielce, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Horodniczy","sequence":"additional","affiliation":[{"name":"ORTHO.PL Ortodonta Zdrowego U\u015bmiechu Dzieci i Doros\u0142ych Wroc\u0142aw, Buforowa 34, 52-131 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Ch\u0119ci\u0144ska","sequence":"additional","affiliation":[{"name":"National Medical Institute of the Ministry of the Interior and Administration, Wo\u0142oska 137, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8075-9989","authenticated-orcid":false,"given":"Natalia","family":"Turosz","sequence":"additional","affiliation":[{"name":"National Medical Institute of the Ministry of the Interior and Administration, Wo\u0142oska 137, 02-507 Warsaw, Poland"},{"name":"Department of Maxillofacial Surgery, Hospital of the Ministry of the Interior and Administration, Wojska Polskiego 51, 25-375 Kielce, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalina","family":"Roma\u0144czyk","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Preventive Medicine Center, Komorowskiego 12, 30-106 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4345-5657","authenticated-orcid":false,"given":"Amelia","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Preventive Medicine Center, Komorowskiego 12, 30-106 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3348-1950","authenticated-orcid":false,"given":"Maciej","family":"Sikora","sequence":"additional","affiliation":[{"name":"National Medical Institute of the Ministry of the Interior and Administration, Wo\u0142oska 137, 02-507 Warsaw, Poland"},{"name":"Department of Maxillofacial Surgery, Hospital of the Ministry of the Interior and Administration, Wojska Polskiego 51, 25-375 Kielce, Poland"},{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.rehab.2016.03.005","article-title":"Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches","volume":"59","author":"Szychlinska","year":"2016","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_2","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."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hill, A., Duran, J., and Purcell, P. (2014). Lubricin Protects the Temporomandibular Joint Surfaces from Degeneration. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106497"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fu, P.-J., Zheng, S.-Y., Luo, Y., Ren, Z.-Q., Li, Z.-H., Wang, Y.-P., and Lu, B.-B. (2025). Prg4 and Osteoarthritis: Functions, Regulatory Factors, and Treatment Strategies. Biomedicines, 13.","DOI":"10.3390\/biomedicines13030693"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3893","DOI":"10.1021\/acs.biomac.3c01348","article-title":"O-Glycans Expand Lubricin and Attenuate Its Viscosity and Shear Thinning","volume":"25","author":"Boushehri","year":"2024","journal-title":"Biomacromolecules"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/eos.12119","article-title":"Transcriptional Regulation of Proteoglycan 4 by 17\u03b2-Estradiol in Immortalized Baboon Temporomandibular Joint Disc Cells","volume":"122","author":"McDaniel","year":"2014","journal-title":"Eur. J. Oral Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"An, H., Liu, Y., Yi, J., Xie, H., Li, C., Wang, X., and Chai, W. (2022). Research Progress of Cartilage Lubrication and Biomimetic Cartilage Lubrication Materials. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.1012653"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bayer, I.S. (2018). Advances in Tribology of Lubricin and Lubricin-Like Synthetic Polymer Nanostructures. Lubricants, 6.","DOI":"10.3390\/lubricants6020030"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"szaf043","DOI":"10.1093\/stcltm\/szaf043","article-title":"Mesenchymal Progenitor\u2013Derived Proteoglycan 4 Regulates the Transdifferentiation of Chondrocytes into Osteoblasts during Fracture Healing","volume":"14","author":"Ninkovic","year":"2025","journal-title":"Stem Cells Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/jop.12273","article-title":"Up-Regulation of Proteoglycan 4 in Temporomandibular Osteoarthritic Synovial Cells by Hyaluronic Acid","volume":"44","author":"Guo","year":"2015","journal-title":"J. Oral Pathol. Med."},{"key":"ref_11","first-page":"e793","article-title":"Lubricin in Synovial Fluid of Mild and Severe Temporomandibular Joint Internal Derangements","volume":"21","author":"Leonardi","year":"2016","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1016\/j.joms.2010.01.018","article-title":"Boundary-Lubricating Ability and Lubricin in Synovial Fluid of Patients with Temporomandibular Joint Disorders","volume":"68","author":"Wei","year":"2010","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Colville, M.J., Huang, L.-T., Schmidt, S., Chen, K., Vishwanath, K., Su, J., Williams, R.M., Bonassar, L.J., Reesink, H.L., and Paszek, M.J. (2024). Recombinant Manufacturing of Multispecies Biolubricants. bioRxiv.","DOI":"10.1101\/2024.05.05.592580"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Iturriaga, V., V\u00e1squez, B., Wen, S., Bornhardt, T., Navarrete, J., and Sol, M. (2025). del Intra-Articular Administration of Recombinant Human Proteoglycan 4 (rhPRG4) as a Potential Therapy for Temporomandibular Joint Osteoarthritis: A Preclinical Histopathological Study. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199305"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jor.23367","article-title":"Reduction of Friction by Recombinant Human Proteoglycan 4 in IL-1\u03b1 Stimulated Bovine Cartilage Explants","volume":"35","author":"Larson","year":"2017","journal-title":"J. Orthop. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112906","DOI":"10.1016\/j.colsurfb.2022.112906","article-title":"Recombinant Lubricin Improves Anti-Adhesive, Wear Protection, and Lubrication of Collagen II Surface","volume":"220","author":"Yuan","year":"2022","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jss.2016.08.092","article-title":"Recombinant Human Lubricin for Prevention of Postoperative Intra-Abdominal Adhesions in a Rat Model","volume":"208","author":"Oh","year":"2017","journal-title":"J. Surg. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101051","DOI":"10.1016\/j.reth.2025.101051","article-title":"Lubricin Maintains Temporomandibular Joint Homeostasis by Regulating Synovial Inflammation","volume":"31","author":"Negishi","year":"2025","journal-title":"Regen. Ther."},{"key":"ref_19","unstructured":"(2026, April 09). ACM Digital Library. Available online: https:\/\/dl.acm.org\/."},{"key":"ref_20","unstructured":"(2026, April 09). BASE\u2014Bielefeld Academic Search Engine|Services. Available online: https:\/\/api.base-search.net\/."},{"key":"ref_21","unstructured":"(2026, April 09). Home|ClinicalTrials.Gov, Available online: https:\/\/clinicaltrials.gov\/."},{"key":"ref_22","unstructured":"(2026, April 09). Cochrane. Available online: https:\/\/www.cochrane.org\/."},{"key":"ref_23","unstructured":"(2026, April 09). Google Scholar. Available online: https:\/\/scholar.google.com\/."},{"key":"ref_24","unstructured":"(2026, April 09). PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/."},{"key":"ref_25","unstructured":"(2026, April 09). Scopus\u2014Sources. Available online: https:\/\/www.scopus.com\/sources."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e011458","DOI":"10.1136\/bmjopen-2016-011458","article-title":"Development of a Critical Appraisal Tool to Assess the Quality of Cross-Sectional Studies (AXIS)","volume":"6","author":"Downes","year":"2016","journal-title":"BMJ Open"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Roggio, F., Petrigna, L., Trovato, B., Di Rosa, M., and Musumeci, G. (2023). The Role of Lubricin, Irisin and Exercise in the Prevention and Treatment of Osteoarthritis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065126"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"666","DOI":"10.33594\/000000818","article-title":"Knee Joint Response to Mechanical Loading: Bounding Mechanotransduction with Rehabilitation","volume":"59","author":"Swinnen","year":"2025","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6194","DOI":"10.1073\/pnas.0608558104","article-title":"The Role of Lubricin in the Mechanical Behavior of Synovial Fluid","volume":"104","author":"Jay","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","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. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1177\/0363546516686965","article-title":"Intra-articular recombinant human proteoglycan 4 mitigates cartilage damage after destabilization of the medial meniscus in the Yucatan minipig","volume":"45","author":"Waller","year":"2017","journal-title":"Am. J. Sports Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100598","DOI":"10.1016\/j.modpat.2024.100598","article-title":"Chondroid Synoviocytic Neoplasm: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of a Distinctive Tumor of Synoviocytes","volume":"37","author":"Kao","year":"2024","journal-title":"Mod. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Qadri, M.M. (2023). Targeting CD44 Receptor Pathways in Degenerative Joint Diseases: Involvement of Proteoglycan-4 (PRG4). Pharmaceuticals, 16.","DOI":"10.3390\/ph16101425"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Demerjian, G.G., Barkhordarian, A., and Chiappelli, F. (2018). Lubricin: Toward a Molecular Mechanism for Temporomandibular Joint Disorders. Temporomandibular Joint and Airway Disorders, Springer International Publishing.","DOI":"10.1007\/978-3-319-76367-5"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/odi.12760","article-title":"Glucosamine Oral Administration as an Adjunct to Hyaluronic Acid Injection in Treating Temporomandibular Joint Osteoarthritis","volume":"24","author":"Cen","year":"2018","journal-title":"Oral Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/j.1600-0714.2011.01012.x","article-title":"Lubricin Immunohistochemical Expression in Human Temporomandibular Joint Disc with Internal Derangement","volume":"40","author":"Leonardi","year":"2011","journal-title":"J. Oral Pathol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.tripleo.2009.11.007","article-title":"Effects of Intra-Articular Administration of Sodium Hyaluronate on Plasminogen Activator System in Temporomandibular Joints with Osteoarthritis","volume":"109","author":"Tang","year":"2010","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1159\/000070570","article-title":"\u2018Friction and Adhesive Forces\u2019\u2014Possible Underlying Causes for Temporomandibular Joint Internal Derangement","volume":"174","author":"Nitzan","year":"2003","journal-title":"Cells Tissues Organs"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/5035\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:46:00Z","timestamp":1780634760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/5035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":38,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27115035"],"URL":"https:\/\/doi.org\/10.3390\/ijms27115035","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]}}}