{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:03:41Z","timestamp":1791277421442,"version":"4.1.0"},"reference-count":101,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,12,18]],"date-time":"2015-12-18T00:00:00Z","timestamp":1450396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1R01AR064242-010A1"],"award-info":[{"award-number":["1R01AR064242-010A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JDB"],"abstract":"<jats:p>Articular cartilage (AC) covers the diarthrodial joints and is responsible for the mechanical distribution of loads across the joints. The majority of its structure and function is controlled by chondrocytes that regulate Extracellular Matrix (ECM) turnover and maintain tissue homeostasis. Imbalance in their function leads to degenerative diseases like Osteoarthritis (OA). OA is characterized by cartilage degradation, osteophyte formation and stiffening of joints. Cartilage degeneration is a consequence of chondrocyte hypertrophy along with the expression of proteolytic enzymes. Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) are an example of these enzymes that degrade the ECM. Signaling cascades involved in limb patterning and cartilage repair play a role in OA progression. However, the regulation of these remains to be elucidated. Further the role of stem cells and mature chondrocytes in OA progression is unclear. The progress in cell based therapies that utilize Mesenchymal Stem Cell (MSC) infusion for cartilage repair may lead to new therapeutics in the long term. However, many questions are unanswered such as the efficacy of MSCs usage in therapy. This review focuses on the role of chondrocytes in cartilage formation and the progression of OA. Moreover, it summarizes possible alternative therapeutic approaches using MSC infusion for cartilage restoration.<\/jats:p>","DOI":"10.3390\/jdb3040177","type":"journal-article","created":{"date-parts":[[2015,12,18]],"date-time":"2015-12-18T10:15:04Z","timestamp":1450433704000},"page":"177-192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":422,"title":["Role of Chondrocytes in Cartilage Formation, Progression of Osteoarthritis and Cartilage Regeneration"],"prefix":"10.3390","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0729-4067","authenticated-orcid":false,"given":"Hemanth","family":"Akkiraju","sequence":"first","affiliation":[{"name":"Biological Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Nohe","sequence":"additional","affiliation":[{"name":"Biological Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.csm.2004.08.007","article-title":"Basic science of articular cartilage and osteoarthritis","volume":"24","author":"Pearle","year":"2005","journal-title":"Clin. Sports Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S1357-2725(02)00301-1","article-title":"The chondrocyte","volume":"35","author":"Archer","year":"2003","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/scrt49","article-title":"Mesenchymal chondroprogenitor cell origin and therapeutic potential","volume":"2","author":"Barry","year":"2011","journal-title":"Stem Cell Res. Ther."},{"key":"ref_4","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":"Kapoor","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1007\/s11999-011-1857-3","article-title":"The role of growth factors in cartilage repair","volume":"469","author":"Fortier","year":"2011","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1136\/ard.2008.098764","article-title":"Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism","volume":"67","author":"Goldring","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1469-7580.1997.19110001.x","article-title":"Articular cartilage chondrons: Form, function and failure","volume":"191","author":"Poole","year":"1997","journal-title":"J. Anat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/1941738109350438","article-title":"The basic science of articular cartilage: Structure, composition, and function","volume":"1","author":"Bedi","year":"2009","journal-title":"Sports Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/ar380","article-title":"Collagen of articular cartilage","volume":"4","author":"Eyre","year":"2002","journal-title":"Arthritis Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/jemt.1070280505","article-title":"Cartilage proteoglycans: Structure and potential functions","volume":"28","author":"Roughley","year":"1994","journal-title":"Microsc Res. Tech."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1136\/ard.61.suppl_2.ii78","article-title":"Type II collagen degradation and its regulation in articular cartilage in osteoarthritis","volume":"61","author":"Poole","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39027","DOI":"10.1074\/jbc.M006700200","article-title":"Effect of collagen turnover on the accumulation of advanced glycation end products","volume":"275","author":"Verzijl","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/0049-0172(90)90044-G","article-title":"Proteoglycans of articular cartilage: Changes in aging and in joint disease","volume":"20","author":"Hardingham","year":"1990","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"B172","DOI":"10.1093\/gerona\/56.4.B172","article-title":"Telomere erosion and senescence in human articular cartilage chondrocytes","volume":"56","author":"Martin","year":"2001","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/jor.1100150403","article-title":"Age-related decline in chondrocyte response to insulin-like growth factor-I: The role of growth factor binding proteins","volume":"15","author":"Martin","year":"1997","journal-title":"J. Orthop. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19805","DOI":"10.3390\/ijms141019805","article-title":"Interplay between cartilage and subchondral bone contributing to pathogenesis of osteoarthritis","volume":"14","author":"Sharma","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3831","DOI":"10.1002\/art.24069","article-title":"Increased hydraulic conductance of human articular cartilage and subchondral bone plate with progression of osteoarthritis","volume":"58","author":"Hwang","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/ar148","article-title":"Articular cartilage and changes in arthritis. An introduction: Cell biology of osteoarthritis","volume":"3","author":"Sandell","year":"2001","journal-title":"Arthritis Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00264-010-0959-y","article-title":"Treatment of articular cartilage lesions of the knee","volume":"34","author":"Falah","year":"2010","journal-title":"Int. Orthop."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.joca.2004.08.008","article-title":"Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage","volume":"12","author":"Wang","year":"2004","journal-title":"Osteoarthr. Cartil."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1083\/jcb.200211089","article-title":"Type X collagen gene regulation by RUNX2 contributes directly to its hypertrophic chondrocyte-specific expression in vivo","volume":"162","author":"Zheng","year":"2003","journal-title":"J. Cell. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.joca.2011.12.003","article-title":"Chondrocyte hypertrophy and osteoarthritis: Role in initiation and progression of cartilage degeneration?","volume":"20","year":"2012","journal-title":"Osteoarthr. Cartil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5625","DOI":"10.1016\/S0021-9258(19)67640-4","article-title":"Sites of stromelysin cleavage in collagen types II, IX, X, and XI of cartilage","volume":"266","author":"Wu","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.bbapap.2011.06.020","article-title":"Proteases involved in cartilage matrix degradation in osteoarthritis","volume":"1824","author":"Troeberg","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/S0014-5793(99)00897-2","article-title":"Stimulation of angiogenesis through cathepsin B inactivation of the tissue inhibitors of matrix metalloproteinases","volume":"455","author":"Kostoulas","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1177\/1947603513495889","article-title":"The roles of mechanical stresses in the pathogenesis of osteoarthritis: Implications for treatment of joint injuries","volume":"4","author":"Buckwalter","year":"2013","journal-title":"Cartilage"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"507","DOI":"10.2741\/2078","article-title":"Mechanical regulation of matrix metalloproteinases","volume":"12","author":"Blain","year":"2007","journal-title":"Front. Biosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.joca.2004.02.012","article-title":"Increased stromelysin-1 (MMP-3), proteoglycan degradation (3B3- and 7D4) and collagen damage in cyclically load-injured articular cartilage","volume":"12","author":"Lin","year":"2004","journal-title":"Osteoarthr. Cartil."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1002\/art.10623","article-title":"Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: A randomized, double-blind, placebo-controlled, dose-escalation trial","volume":"46","author":"Choy","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1002\/art.1780390914","article-title":"Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis. Suppression of collagenase-1 expression","volume":"39","author":"Caron","year":"1996","journal-title":"Arthritis Rheum."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/art.1780380204","article-title":"Role of interleukin-1, tumor necrosis factor alpha, and interleukin-6 in cartilage proteoglycan metabolism and destruction. Effect of in situ blocking in murine antigen- and zymosan-induced arthritis","volume":"38","author":"Joosten","year":"1995","journal-title":"Arthritis Rheum."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nm.2146","article-title":"Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development","volume":"16","author":"Saito","year":"2010","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/j.joca.2010.08.016","article-title":"Circulating levels of IL-6 and TNF-\u03b1 are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults","volume":"18","author":"Stannus","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1016\/j.biocel.2013.08.018","article-title":"The NF-\u03baB signalling pathway in osteoarthritis","volume":"45","author":"Rigoglou","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/art.24352","article-title":"Interleukin-1beta and tumor necrosis factor alpha inhibit chondrogenesis by human mesenchymal stem cells through NF-kappaB-dependent pathways","volume":"60","author":"Wehling","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1053\/joca.2001.0505","article-title":"Development and regulation of osteophyte formation during experimental osteoarthritis","volume":"10","author":"Hashimoto","year":"2002","journal-title":"Osteoarthr. Cartil."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11914-014-0192-5","article-title":"Osteoblast-chondrocyte interactions in osteoarthritis","volume":"12","author":"Findlay","year":"2014","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1093\/rheumatology\/kev228","article-title":"Unravelling osteoarthritis-related synovial fibrosis: A step closer to solving joint stiffness","volume":"54","author":"Remst","year":"2015","journal-title":"Rheumatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S1063-4584(97)80003-9","article-title":"Gene expression of type II collagens in chondro-osteophytes in experimental osteoarthritis","volume":"5","author":"Matyas","year":"1997","journal-title":"Osteoarthr. Cartil."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.joca.2004.03.003","article-title":"Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis","volume":"12","author":"Blom","year":"2004","journal-title":"Osteoarthr. Cartil."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1053\/joca.2002.0873","article-title":"Osteophyte development\u2014Molecular characterization of differentiation stages","volume":"11","author":"Gelse","year":"2003","journal-title":"Osteoarthr. Cartil."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.pharmthera.2015.03.006","article-title":"Pericytes, mesenchymal stem cells and their contributions to tissue repair","volume":"151","author":"Wong","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1053\/joca.1998.0129","article-title":"Differential effects of local application of BMP-2 or TGF-beta 1 on both articular cartilage composition and osteophyte formation","volume":"6","author":"Glansbeek","year":"1998","journal-title":"Osteoarthr. Cartil."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/00003086-200008000-00017","article-title":"Growth factor expression in the osteophytes of the human femoral head in osteoarthritis","volume":"377","author":"Uchino","year":"2000","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_47","first-page":"331","article-title":"Macrophages, synovial tissue and rheumatoid arthritis","volume":"11","author":"Cutolo","year":"1993","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/S8756-3282(01)00638-X","article-title":"Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2","volume":"30","author":"Champagne","year":"2002","journal-title":"Bone"},{"key":"ref_49","first-page":"236","article-title":"Differential expression of collagen types I, II, III, and X in human osteophytes","volume":"73","author":"Aigner","year":"1995","journal-title":"Lab. Invest."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.0022-202X.2003.22133.x","article-title":"Insights into the molecular mechanism of chronic fibrosis: The role of connective tissue growth factor in scleroderma","volume":"122","author":"Leask","year":"2004","journal-title":"J. Invest. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1096\/fj.03-1273rev","article-title":"TGF-beta signaling and the fibrotic response","volume":"18","author":"Leask","year":"2004","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6697","DOI":"10.1074\/jbc.M807859200","article-title":"Growth factor regulation of growth factors in articular chondrocytes","volume":"284","author":"Shi","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8667","DOI":"10.3390\/ijms15058667","article-title":"Signaling pathways in cartilage repair","volume":"15","author":"Mariani","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"R130","DOI":"10.1186\/ar3441","article-title":"Fibroblast growth factor receptor 1 is principally responsible for fibroblast growth factor 2-induced catabolic activities in human articular chondrocytes","volume":"13","author":"Yan","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Shintani, N., Siebenrock, K.A., and Hunziker, E.B. (2013). Tgf-\u03b21 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053086"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"R102","DOI":"10.1186\/ar2305","article-title":"Elevated extracellular matrix production and degradation upon bone morphogenetic protein-2 (BMP-2) stimulation point toward a role for BMP-2 in cartilage repair and remodeling","volume":"9","author":"Vitters","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"R82","DOI":"10.1186\/ar3805","article-title":"Bone morphogenetic protein-2-induced Wnt\/\u03b2-catenin signaling pathway activation through enhanced low-density-lipoprotein receptor-related protein 5 catabolic activity contributes to hypertrophy in osteoarthritic chondrocytes","volume":"14","author":"Papathanasiou","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/jcb.20652","article-title":"The control of chondrogenesis","volume":"97","author":"Goldring","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e000061","DOI":"10.1136\/rmdopen-2015-000061","article-title":"Pathophysiology of osteoarthritis: Canonical NF-kappaB\/IKKbeta-dependent and kinase-independent effects of IKKalpha in cartilage degradation and chondrocyte differentiation","volume":"1","author":"Olivotto","year":"2015","journal-title":"RMD Open"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.joca.2010.03.001","article-title":"Bone morphogenetic proteins and articular cartilage: To serve and protect or a wolf in sheep clothing\u2019s?","volume":"18","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1242\/dev.029926","article-title":"BMP canonical smad signaling through Smad1 and Smad5 is required for endochondral bone formation","volume":"136","author":"Retting","year":"2009","journal-title":"Development"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S1063-4584(03)00004-9","article-title":"Localization of bone morphogenetic protein-2 in human osteoarthritic cartilage and osteophyte","volume":"11","author":"Nakase","year":"2003","journal-title":"Osteoarthr. Cartil."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1046\/j.1469-7580.2003.00158.x","article-title":"Expression of bone morphogenetic proteins and cartilage-derived morphogenetic proteins during osteophyte formation in humans","volume":"202","author":"Zoricic","year":"2003","journal-title":"J. Anat."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/ar3837","article-title":"The interaction of canonical bone morphogenetic protein- and Wnt-signaling pathways may play an important role in regulating cartilage degradation in osteoarthritis","volume":"14","author":"Chan","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.joca.2009.06.008","article-title":"TGF-beta signaling in chondrocyte terminal differentiation and osteoarthritis: Modulation and integration of signaling pathways through receptor-smads","volume":"17","author":"Blom","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/art.24247","article-title":"Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: Prominent role of Wnt-induced signaling protein 1","volume":"60","author":"Blom","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/(SICI)1521-1878(200002)22:2<138::AID-BIES5>3.0.CO;2-4","article-title":"All for one and one for all: Condensations and the initiation of skeletal development","volume":"22","author":"Hall","year":"2000","journal-title":"Bioessays"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1053\/joca.1999.0306","article-title":"Cellular interactions and signaling in cartilage development","volume":"8","author":"DeLise","year":"2000","journal-title":"Osteoarthr. Cartil."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2106\/00004623-200300002-00019","article-title":"Cellular signaling in developmental chondrogenesis: N-cadherin, Wnts, and BMP-2","volume":"85-A","author":"Tuan","year":"2003","journal-title":"J. Bone Joint Surg. Am."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1046\/j.1474-9728.2002.00008.x","article-title":"The role of chondrocyte senescence in osteoarthritis","volume":"1","author":"Price","year":"2002","journal-title":"Aging Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"619","DOI":"10.3233\/BIR-1981-183-624","article-title":"Measurement of swelling pressure in cartilage and comparison with the osmotic pressure of constituent proteoglycans","volume":"18","author":"Maroudas","year":"1981","journal-title":"Biorheology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3233\/BIR-1979-16609","article-title":"Swelling pressures of proteoglycans at the concentrations found in cartilaginous tissues","volume":"16","author":"Urban","year":"1979","journal-title":"Biorheology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.joca.2007.02.022","article-title":"Chondrocyte moves: Clever strategies?","volume":"15","author":"Morales","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S1063-4584(05)80320-6","article-title":"Ultrastructural study of chondrocytes from fibrillated and non-fibrillated human osteoarthritic cartilage","volume":"4","author":"Kouri","year":"1996","journal-title":"Osteoarthr. Cartil."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1002\/art.23485","article-title":"Synovial fluid mesenchymal stem cells in health and early osteoarthritis: Detection and functional evaluation at the single-cell level","volume":"58","author":"Jones","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"119","DOI":"10.14712\/fb2011057030119","article-title":"Isolation and characterization of synovial mesenchymal stem cells","volume":"57","author":"Rosocha","year":"2011","journal-title":"Folia Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1097\/00003086-199311000-00047","article-title":"Bone morphogenetic protein-induced muscle- and synovium-derived cartilage differentiation in vitro","volume":"296","author":"Iwata","year":"1993","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1002\/jor.20659","article-title":"Autologous synovial fluid enhances migration of mesenchymal stem cells from synovium of osteoarthritis patients in tissue culture system","volume":"26","author":"Zhang","year":"2008","journal-title":"J. Orthop. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1469-7580.2009.01115.x","article-title":"Identification of a stem cell niche in the zone of ranvier within the knee joint","volume":"215","author":"Karlsson","year":"2009","journal-title":"J. Anat."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1302\/0301-620X.85B5.13587","article-title":"Tissue-engineered cartilage and bone using stem cells from human infrapatellar fat pads","volume":"85","author":"Dragoo","year":"2003","journal-title":"J. Bone Joint Surg. Br."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1002\/1529-0131(200108)44:8<1928::AID-ART331>3.0.CO;2-P","article-title":"Multipotent mesenchymal stem cells from adult human synovial membrane","volume":"44","author":"Tylzanowski","year":"2001","journal-title":"Arthritis Rheum."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.matbio.2014.08.015","article-title":"Resident mesenchymal progenitors of articular cartilage","volume":"39","author":"Candela","year":"2014","journal-title":"Matrix Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s00441-006-0308-z","article-title":"Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle","volume":"327","author":"Yoshimura","year":"2007","journal-title":"Cell Tissue Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"R85","DOI":"10.1186\/ar2719","article-title":"Mesenchymal progenitor cell markers in human articular cartilage: Normal distribution and changes in osteoarthritis","volume":"11","author":"Grogan","year":"2009","journal-title":"Arthritis Res. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1478-811X-9-12","article-title":"Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC","volume":"9","author":"Hass","year":"2011","journal-title":"Cell. Commun. Signal."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/scrt116","article-title":"Mesenchymal stem cells for cartilage repair in osteoarthritis","volume":"3","author":"Gupta","year":"2012","journal-title":"Stem Cell Res. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1126\/science.276.5309.71","article-title":"Marrow stromal cells as stem cells for nonhematopoietic tissues","volume":"276","author":"Prockop","year":"1997","journal-title":"Science"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1177\/0363546509359067","article-title":"Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: An observational cohort study","volume":"38","author":"Nejadnik","year":"2010","journal-title":"Am. J. Sports Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.1016\/j.biomaterials.2006.03.017","article-title":"The differentiation of bone marrow mesenchymal stem cells into chondrocyte-like cells on poly-l-lactic acid (PLLA) scaffolds","volume":"27","author":"Richardson","year":"2006","journal-title":"Biomaterials"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.joca.2008.01.004","article-title":"Characterization of proteoglycan production and processing by chondrocytes and bmscs in tissue engineered constructs","volume":"16","author":"Connelly","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"a015479","DOI":"10.1101\/cshperspect.a015479","article-title":"The innate immune system and transplantation","volume":"3","author":"Farrar","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"975871","DOI":"10.1155\/2012\/975871","article-title":"Markers for characterization of bone marrow multipotential stromal cells","volume":"2012","author":"Boxall","year":"2012","journal-title":"Stem Cells Int."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1089\/scd.2007.0217","article-title":"Comparative analysis of mesenchymal stem cells from bone marrow, cartilage, and adipose tissue","volume":"17","author":"Peng","year":"2008","journal-title":"Stem Cells Dev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/scrt501","article-title":"Synovial fluid and synovial membrane mesenchymal stem cells: Latest discoveries and therapeutic perspectives","volume":"5","author":"Casado","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1002\/art.21212","article-title":"Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source","volume":"52","author":"Sakaguchi","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.1002\/art.10696","article-title":"Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells","volume":"46","author":"Jones","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"R74","DOI":"10.1186\/ar2448","article-title":"Human infrapatellar fat pad-derived stem cells express the pericyte marker 3G5 and show enhanced chondrogenesis after expansion in fibroblast growth factor-2","volume":"10","author":"Khan","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"546","DOI":"10.2174\/138945010791011866","article-title":"Intraarticular treatments for osteoarthritis: New perspectives","volume":"11","author":"Chevalier","year":"2010","journal-title":"Curr. Drug Targets"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1097\/01.blo.0000143938.30681.9d","article-title":"The impact of osteoarthritis: Implications for research","volume":"427","author":"Buckwalter","year":"2004","journal-title":"Clin. Orthop. Relat. Res."}],"container-title":["Journal of Developmental Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2221-3759\/3\/4\/177\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:54:20Z","timestamp":1760216060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2221-3759\/3\/4\/177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,18]]},"references-count":101,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,12]]}},"alternative-id":["jdb3040177"],"URL":"https:\/\/doi.org\/10.3390\/jdb3040177","relation":{},"ISSN":["2221-3759"],"issn-type":[{"value":"2221-3759","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,18]]}}}