{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:02:38Z","timestamp":1793138558533,"version":"4.5.0"},"reference-count":95,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n Garc\u00eda-Cugat"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Proteoglycans are vital components of the extracellular matrix in articular cartilage, providing biomechanical properties crucial for its proper functioning. They are key players in chondral diseases, specifically in the degradation of the extracellular matrix. Evaluating proteoglycan molecules can serve as a biomarker for joint degradation in osteoarthritis patients, as well as assessing the quality of repaired tissue following different treatment strategies for chondral injuries. Despite ongoing research, understanding osteoarthritis and cartilage repair remains unclear, making the identification of key molecules essential for early diagnosis and effective treatment. This review offers an overview of proteoglycans as primary molecules in articular cartilage. It describes the various types of proteoglycans present in both healthy and damaged cartilage, highlighting their roles. Additionally, the review emphasizes the importance of assessing proteoglycans to evaluate the quality of repaired articular tissue. It concludes by providing a visual and narrative description of aggrecan distribution and presence in healthy cartilage. Proteoglycans, such as aggrecan, biglycan, decorin, perlecan, and versican, significantly contribute to maintaining the health of articular cartilage and the cartilage repair process. Therefore, studying these proteoglycans is vital for early diagnosis, evaluating the quality of repaired cartilage, and assessing treatment effectiveness.<\/jats:p>","DOI":"10.3390\/ijms241310824","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:41:45Z","timestamp":1687999305000},"page":"10824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Proteoglycans in Articular Cartilage and Their Contribution to Chondral Injury and Repair Mechanisms"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3848-9510","authenticated-orcid":false,"given":"Lourdes","family":"Alcaide-Ruggiero","sequence":"first","affiliation":[{"name":"Departamento de Medicina y Cirug\u00eda Animal, Facultad de Veterinaria, Universidad de C\u00f3rdoba, Hospital Cl\u00ednico Veterinario, Campus de Rabanales, Ctra. Madrid-C\u00e1diz Km 396, 14014 C\u00f3rdoba, Spain"},{"name":"Fundaci\u00f3n Garc\u00eda-Cugat, Plaza Alfonso Com\u00edn 5\u20137, 08023 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Cugat","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Garc\u00eda-Cugat, Plaza Alfonso Com\u00edn 5\u20137, 08023 Barcelona, Spain"},{"name":"Instituto Cugat y Mutualidad de Futbolistas Espa\u00f1oles, Delegaci\u00f3n Catalana, 08023 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7627-4767","authenticated-orcid":false,"given":"Juan Manuel","family":"Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Departamento de Medicina y Cirug\u00eda Animal, Facultad de Veterinaria, Universidad de C\u00f3rdoba, Hospital Cl\u00ednico Veterinario, Campus de Rabanales, Ctra. Madrid-C\u00e1diz Km 396, 14014 C\u00f3rdoba, Spain"},{"name":"Fundaci\u00f3n Garc\u00eda-Cugat, Plaza Alfonso Com\u00edn 5\u20137, 08023 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0945-053X(97)90037-8","article-title":"History of extracellular matrix: A personal view","volume":"16","author":"Piez","year":"1997","journal-title":"Matrix Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2015.11.001","article-title":"Extracellular matrix structure","volume":"97","author":"Theocharis","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1097\/IJG.0000000000000108","article-title":"Biology of the extracellular matrix: An overview","volume":"23","author":"Yue","year":"2014","journal-title":"J. Glaucoma."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/bph.14195","article-title":"The extracellular matrix as a key regulator of intracellular signalling networks","volume":"176","author":"Hastings","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s13046-022-02484-1","article-title":"The extracellular matrix alteration, implication in modulation of drug resistance mechanism: Friends or foes?","volume":"41","author":"Jurj","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11320","DOI":"10.1021\/acsnano.9b04477","article-title":"Decorin regulates the aggrecan network integrity and biomechanical functions of cartilage extracellular matrix","volume":"13","author":"Han","year":"2019","journal-title":"ACS Nano"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gilbert, S.J., Bonnet, C.S., and Blain, E.J. (2021). Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413595"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Alcaide-Ruggiero, L., Molina-Hern\u00e1ndez, V., Granados, M.M., and Dom\u00ednguez, J.M. (2021). Main and Minor Types of Collagens in the Articular Cartilage: The Role of Collagens in Repair Tissue Evaluation in Chondral Defects. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413329"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/jor.23757","article-title":"Functional Properties of Chondrocytes and Articular Cartilage using Optical Imaging to Scanning Probe Microscopy","volume":"36","author":"Xia","year":"2018","journal-title":"J. Orthop. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0945-053X(02)00026-4","article-title":"Retention of the native chondrocyte pericellular matrix results in significantly improved matrix production","volume":"21","author":"Larson","year":"2002","journal-title":"Matrix Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"37698","DOI":"10.1074\/jbc.M304638200","article-title":"Complexes of matrilin-1 and biglycan or decorin connect collagen VI microfibrils to both collagen II and aggrecan","volume":"278","author":"Wiberg","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"421","DOI":"10.5435\/00124635-200311000-00006","article-title":"Articular cartilage biology","volume":"11","author":"Maloney","year":"2003","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/bmb\/ldn025","article-title":"Articular cartilage: Structure, injuries and review of management","volume":"87","author":"Bhosale","year":"2008","journal-title":"Br. Med. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/00132585-200609000-00006","article-title":"Articular cartilage: Injury pathways and treatment options","volume":"14","author":"Simon","year":"2006","journal-title":"Sport. Med. Arthrosc. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1126\/science.1222454","article-title":"Unlike bone, cartilage regeneration remains elusive","volume":"338","author":"Huey","year":"2012","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40634-014-0008-7","article-title":"The role of aggrecan in normal and osteoarthritic cartilage","volume":"1","author":"Roughley","year":"2014","journal-title":"J. Exp. Orthop."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0968-0160(01)00133-8","article-title":"Natural progression of osteo-chondral defect in the femoral condyle","volume":"9","author":"Prakash","year":"2002","journal-title":"Knee"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/art.23177","article-title":"Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I","volume":"58","author":"Helmick","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Alberton, P., Dugonitsch, H.C., Hartmann, B., Li, P., Farkas, Z., Saller, M.M., Clausen-Schaumann, H., and Aszodi, A. (2019). Aggrecan hypomorphism compromises articular cartilage biomechanical properties and is associated with increased incidence of spontaneous osteoarthritis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051008"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.matbio.2018.05.005","article-title":"Cartilage diseases","volume":"71\u201372","author":"Krishnan","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_21","first-page":"1","article-title":"Roles of Articular Cartilage Aging and Chondrocyte Senescence in the Pathogenesis of Osteoarthritis","volume":"21","author":"Martin","year":"2001","journal-title":"Iowa Orthop. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Masson, A.O., and Krawetz, R.J. (2020). Understanding cartilage protection in OA and injury: A spectrum of possibilities. BMC Musculoskelet. Disord., 21.","DOI":"10.1186\/s12891-020-03363-6"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"452315","DOI":"10.1155\/2014\/452315","article-title":"Metabolism of cartilage proteoglycans in health and disease","volume":"2014","author":"Vynios","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1111\/febs.12197","article-title":"Recombinant production of proteoglycans and their bioactive domains","volume":"280","author":"Lord","year":"2013","journal-title":"FEBS J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1369\/0022155412464638","article-title":"An introduction to proteoglycans and their localization","volume":"60","author":"Couchman","year":"2012","journal-title":"J. Histochem. Cytochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0021-9258(19)78194-0","article-title":"Proteinpolysaccharide Complex from bovine nasal cartilage: A comparison of low and high shear extraction procedures","volume":"244","author":"Sajdera","year":"1969","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.matbio.2015.02.003","article-title":"Proteoglycan form and function: A comprehensive nomenclature of proteoglycans","volume":"42","author":"Iozzo","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/B978-0-12-800267-4.00006-7","article-title":"Development of mast cells and importance of their tryptase and chymase serine proteases in inflammation and wound healing","volume":"122","author":"Douaiher","year":"2014","journal-title":"Adv. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"327","DOI":"10.3389\/fonc.2013.00327","article-title":"Serglycin: At the crossroad of inflammation and malignancy","volume":"3","author":"Korpetinou","year":"2014","journal-title":"Front. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4927","DOI":"10.4049\/jimmunol.1100806","article-title":"Serglycin: A structural and functional chameleon with wide impact on immune cells","volume":"187","author":"Kolset","year":"2011","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18257","DOI":"10.1074\/jbc.M510330200","article-title":"Identification and characterization of versican\/PG-M aggregates in cartilage","volume":"281","author":"Matsumoto","year":"2006","journal-title":"J Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1369\/0022155412464376","article-title":"The different roles of aggrecan interaction domains","volume":"60","author":"Aspberg","year":"2012","journal-title":"J. Histochem. Cytochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4242","DOI":"10.1016\/S0021-9258(19)42508-8","article-title":"Aggregation of Cartilage Proteoglycans: II. Oligosaccharide competitors of the proteoglycan-hyaluronic acid interaction","volume":"249","author":"Hascall","year":"1974","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nrm3902","article-title":"Extracellular matrix assembly: A multiscale deconstruction","volume":"15","author":"Mouw","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hayes, A.J., and Melrose, J. (2020). Aggrecan, the primary weight-bearing cartilage proteoglycan, has context-dependent, cell-directive properties in embryonic development and neurogenesis: Aggrecan glycan side chain modifications convey interactive biodiversity. Biomolecules, 10.","DOI":"10.3390\/biom10091244"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1007\/s00167-022-07295-7","article-title":"Particulate cartilage and platelet-rich plasma treatment for knee chondral defects in sheep","volume":"31","author":"Morgaz","year":"2023","journal-title":"Knee Surg. Sport. Traumatol. Arthrosc."},{"key":"ref_37","unstructured":"Alcaide-Ruggiero, L., Molina-Hern\u00e1ndez, V., Morgaz, J., Fern\u00e1ndez-Sarmiento, J.A., Granados, M.M., Carrillo, J.M., Cugat, R., and Dom\u00ednguez, J.M. (2023, January 17\u201319). Reparaci\u00f3n de defectos condrales de rodilla en ovejas tras el tratamiento con cart\u00edlago aut\u00f3logo particulado y plasma rico en plaquetas. Proceedings of the XXVII Congreso Internacional de la Sociedad Espa\u00f1ola de Cirug\u00eda Veterinaria, Alicante, Spain."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.ajpath.2012.04.029","article-title":"Decorin: A Guardian from the Matrix","volume":"181","author":"Neill","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1369\/0022155412456380","article-title":"Biglycan: A Multivalent Proteoglycan Providing Structure and Signals","volume":"60","author":"Nastase","year":"2012","journal-title":"J. Histochem. Cytochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.joca.2021.03.019","article-title":"Differentiated activities of decorin and biglycan in the progression of post-traumatic osteoarthritis","volume":"29","author":"Han","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1369\/0022155420937371","article-title":"Biglycan in the skeleton","volume":"68","author":"Kram","year":"2020","journal-title":"J. Histochem. Cytochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1186\/ar326","article-title":"Articular cartilage and changes in arthritis noncollagenous proteins and proteoglycans in the extracellular matrix of cartilage","volume":"3","author":"Roughley","year":"2001","journal-title":"Arthritis Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1369\/0022155420953922","article-title":"Versican: A dynamic regulator of the extracellular matrix","volume":"68","author":"Islam","year":"2020","journal-title":"J. Histochem. Cytochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21114","DOI":"10.1074\/jbc.M109.096479","article-title":"Versican facilitates chondrocyte differentiation and regulates joint morphogenesis","volume":"285","author":"Choocheep","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s10735-019-09823-1","article-title":"Type XI collagen-perlecan-HS interactions stabilise the pericellular matrix of annulus fibrosus cells and chondrocytes providing matrix stabilisation and homeostasis","volume":"50","author":"Smith","year":"2019","journal-title":"J. Mol. Hist."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11174","DOI":"10.1021\/bi8013938","article-title":"Diverse cell signaling events modulated by perlecan","volume":"47","author":"Whitelock","year":"2008","journal-title":"Biochemistry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"856261","DOI":"10.3389\/fcell.2022.856261","article-title":"Perlecan, A multi-functional, cell-instructive, matrix-stabilizing proteoglycan with roles in tissue development has relevance to connective tissue repair and regeneration","volume":"10","author":"Hayes","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Guilak, F., Hayes, A.J., and Melrose, J. (2021). Perlecan in pericellular mechanosensory cell-matrix communication, extracellular matrix stabilisation and mechanoregulation of load-bearing connective tissues. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052716"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1089\/scd.2016.0054","article-title":"The CS Sulfation Motifs 4C3, 7D4, 3B3[\u2212]; and perlecan identify stem cell populations and their niches, activated progenitor cells and transitional areas of tissue development in the fetal human elbow","volume":"25","author":"Hayes","year":"2016","journal-title":"Stem Cells Dev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nrrheum.2010.198","article-title":"The role of the cartilage matrix in osteoarthritis","volume":"7","author":"Saxne","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/jor.1100050406","article-title":"Chondrons in cartilage: Ultrastructural analysis of the pericellular microenvironment in adult human articular cartilages","volume":"5","author":"Poole","year":"1987","journal-title":"J. Orthop. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"237","DOI":"10.22203\/eCM.v027a17","article-title":"Roles of type VI collagen and decorin in human mesenchymal stem cell biophysics during chondrogenic differentiation","volume":"27","author":"Twomey","year":"2014","journal-title":"Eur. Cells Mater."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"40","DOI":"10.22203\/eCM.v032a03","article-title":"Pericellular colocalisation and interactive properties of type VI collagen and perlecan in the intervertebral disc","volume":"32","author":"Hayes","year":"2016","journal-title":"Eur. Cells Mater."},{"key":"ref_54","first-page":"5658","article-title":"Evaluation of correlation of articular cartilage staining for DDR2 and proteoglycans with histological tissue damage and the results of radiographic assessment in patients with early stages of knee osteoarthritis","volume":"8","author":"Suutre","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1177\/0022034508330432","article-title":"Proteoglycans and mechanical behavior of condylar cartilage","volume":"88","author":"Lu","year":"2009","journal-title":"J. Dent. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3233\/BIR-1985-22206","article-title":"Studies of hydration and swelling pressure in normal and osteoarthritic cartilage","volume":"22","author":"Maroudas","year":"1985","journal-title":"Biorheology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1042\/bj3580615","article-title":"Analysis of aggrecan in human knee cartilage and synovial fluid indicates that aggrecanase (ADAMTS) activity is responsible for the catabolic turnover and loss of whole aggrecan whereas other protease activity is required for C-terminal processing in vivo","volume":"358","author":"Sandy","year":"2001","journal-title":"Biochem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5574582","DOI":"10.1155\/2021\/5574582","article-title":"Biomarkers of Joint Damage in Osteoarthritis: Current Status and Future Directions","volume":"2021","author":"Kumavat","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"R230","DOI":"10.1186\/ar3217","article-title":"Association between synovial fluid levels of aggrecan ARGS fragments and radiographic progression in knee osteoarthritis","volume":"12","author":"Larsson","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/jor.1100140502","article-title":"Contents and distributions of the proteoglycans decorin and biglycan in normal and osteoarthritic human articular cartilage","volume":"14","author":"Poole","year":"1996","journal-title":"J. Orthop. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.joca.2014.04.026","article-title":"The role of small leucine-rich proteoglycans in osteoarthritis pathogenesis","volume":"22","author":"Ni","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1136\/annrheumdis-2016-209319","article-title":"Forced exercise-induced osteoarthritis is attenuated in mice lacking the small leucine-rich proteoglycan decorin","volume":"76","author":"Gronau","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1186\/s13075-015-0902-0","article-title":"Soluble biglycan: A potential mediator of cartilage degradation in osteoarthritis","volume":"17","author":"Barreto","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1681\/ASN.2014010117","article-title":"beyond tissue injury\u2014Damage-associated molecular patterns, toll-like receptors, and inflammasomes also drive regeneration and fibrosis","volume":"25","author":"Anders","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1159\/000075029","article-title":"Perlecan functions in chondrogenesis: Insights from in vitro and in vivo models","volume":"176","author":"Gomes","year":"2004","journal-title":"Cells Tissues Organs."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Garcia, J., McCarthy, H.S., Kuiper, J.H., Melrose, J., and Roberts, S. (2021). Perlecan in the natural and cell therapy repair of human adult articular cartilage: Can modifications in this proteoglycan be a novel therapeutic approach?. Biomolecules, 11.","DOI":"10.3390\/biom11010092"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.actbio.2021.08.032","article-title":"Impact of perlecan, a core component of basement membrane, on regeneration of cartilaginous tissues","volume":"135","author":"Gao","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/bies.20748","article-title":"Perlecan, the \u201cjack of all trades\u201d proteoglycan of cartilaginous weight-bearing connective tissues","volume":"30","author":"Melrose","year":"2008","journal-title":"BioEssays"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.joca.2004.07.004","article-title":"Perlecan in late stages of osteoarthritis of the human knee joint","volume":"12","author":"Tesche","year":"2004","journal-title":"Osteoarthr. Cartil."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Biomarkers Definitions Working Group (2001). Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin. Pharmacol. Ther., 69, 89\u201395.","DOI":"10.1067\/mcp.2001.113989"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3109\/1354750X.2016.1140930","article-title":"Biomarkers of (osteo)arthritis","volume":"20","author":"Mobasheri","year":"2015","journal-title":"Biomarkers"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"82S","DOI":"10.1177\/1947603520942941","article-title":"Synovial Fluid Biomarkers in Knee Osteoarthritis: A Systematic Reviewand Quantitative Evaluation Using BIPEDs Criteria","volume":"13","author":"Boffa","year":"2021","journal-title":"Cartilage"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.bone.2011.11.019","article-title":"Diagnosis of Osteoarthritis: Imaging","volume":"51","author":"Braun","year":"2012","journal-title":"Bone"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3668568","DOI":"10.1155\/2021\/3668568","article-title":"Effect of Resveratrol on Serum Levels of Type II Collagen and Aggrecan in Patients with Knee Osteoarthritis: A Pilot Clinical Study","volume":"2021","author":"Marouf","year":"2021","journal-title":"BioMed Res. Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1365-2613.2009.00695.x","article-title":"Proteoglycans and more-from molecules to biology","volume":"90","year":"2009","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/BOR.0000000000000845","article-title":"Blood and urine biomarkers in osteoarthritis\u2014An update on cartilage associated type II collagen and aggrecan markers","volume":"34","author":"Mobasheri","year":"2022","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/ar2735","article-title":"Synovial fluid level of aggrecan ARGS fragments is a more sensitive marker of joint disease than glycosaminoglycan or aggrecan levels: A cross-sectional study","volume":"11","author":"Larsson","year":"2009","journal-title":"Arthritis Res. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1002\/anr.1780321113","article-title":"Increased levels of proteoglycan fragments in knee joint fluid after injury","volume":"32","author":"Lohmander","year":"1989","journal-title":"Arthritis Rheum."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"453","DOI":"10.4103\/ijmr.IJMR_2020_18","article-title":"Relationship between increased serum & synovial fluid decorin levels & knee osteoarthritis","volume":"153","author":"Ozler","year":"2021","journal-title":"Indian J. Med. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"11","DOI":"10.53350\/pjmhs20221611324","article-title":"Validation of Levels of Decorin as A Reliable Biomarker of Osteoarthritis: Comparison of Serum and Synovial Fluid Levels","volume":"16","author":"Anwar","year":"2022","journal-title":"Pak. J. Med. Health Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1308\/003588412X13171221592573","article-title":"The present state of treatments for articular cartilage defects in the knee","volume":"94","author":"Perera","year":"2012","journal-title":"Ann. R. Coll. Surg. Engl."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1177\/1947603519833144","article-title":"Knee Cartilage Defect Characteristics Vary among SymptomaticRecreational and Competitive Scholastic Athletes Eligible for Cartilage Restoration Surgery","volume":"12","author":"Everhart","year":"2021","journal-title":"Cartilage"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jmbbm.2019.05.040","article-title":"Combined enzymatic degradation of proteoglycans and collagen significantly alters intratissue strains in articular cartilage during cyclic compression","volume":"98","author":"Pastrama","year":"2019","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1021\/acs.jproteome.5b00946","article-title":"Elucidating the Molecular Composition of Cartilage by Proteomics","volume":"15","author":"Hsueh","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"R59","DOI":"10.1186\/ar4231","article-title":"A novel in vitro bovine cartilage punch model for assessing the regeneration of focal cartilage defects with biocompatible bacterial nanocellulose","volume":"15","author":"Pretzel","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Mori, H., Kondo, E., Kawaguchi, Y., Kitamura, N., Nagai, N., Iida, H., and Yasuda, K. (2013). Development of a salmon-derived crosslinked atelocollagen sponge disc containing osteogenic protein-1 for articular cartilage regeneration: In vivo evaluations with rabbits. BMC Musculoskelet. Disord., 14.","DOI":"10.1186\/1471-2474-14-174"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/rb\/rbz039","article-title":"Platelet-rich plasma combined with injectable hyaluronic acid hydrogel for porcine cartilage regeneration: A 6-month follow-up","volume":"7","author":"Yan","year":"2019","journal-title":"Regen. Biomater."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2325967119867618","DOI":"10.1177\/2325967119867618","article-title":"Chondrocytes From device-minced articular cartilage show potent outgrowth into fibrin and collagen hydrogels","volume":"7","author":"Levinson","year":"2019","journal-title":"Orthop. J. Sport. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.2147\/CIA.S140976","article-title":"REAC regenerative treatment efficacy in experimental chondral lesions: A pilot study on ovine animal model","volume":"12","author":"Passino","year":"2017","journal-title":"Clin. Interv. Aging"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1089\/ten.tec.2017.0109","article-title":"Age-dependent subchondral bone remodeling and cartilage repair in a minipig defect model","volume":"23","author":"Pfeifer","year":"2017","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1021\/acsnano.5b06663","article-title":"Photo-cross-linked scaffold with kartogenin-encapsulated nanoparticles for cartilage regeneration","volume":"10","author":"Shi","year":"2016","journal-title":"ACS Nano"},{"key":"ref_92","first-page":"617365","article-title":"Articular Cartilage Repair Using Marrow Stimulation Augmented with a Viable Chondral Allograft: 9-Month Postoperative Histological Evaluation","volume":"2015","author":"Hoffman","year":"2015","journal-title":"Case Rep. Orthop."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40634-015-0031-3","article-title":"Experimental articular cartilage repair in the G\u00f6ttingen minipig: The influence of multiple defects per knee","volume":"2","author":"Christensen","year":"2015","journal-title":"J. Exp. Orthop."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"16225","DOI":"10.1038\/srep16225","article-title":"A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: A pilot study","volume":"5","author":"Peck","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.joca.2010.03.013","article-title":"The effect of platelet rich plasma combined with microfractures on the treatment of chondral defects: An experimental study in a sheep model","volume":"18","author":"Milano","year":"2010","journal-title":"Osteoarthr. Cartil."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10824\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:03:10Z","timestamp":1760126590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,28]]},"references-count":95,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241310824"],"URL":"https:\/\/doi.org\/10.3390\/ijms241310824","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,28]]}}}