{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T12:42:29Z","timestamp":1771332149704,"version":"3.50.1"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T00:00:00Z","timestamp":1687651200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T00:00:00Z","timestamp":1687651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2014-04586"],"award-info":[{"award-number":["RGPIN-2014-04586"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"crossref","award":["JELF"],"award-info":[{"award-number":["JELF"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012260","name":"Calgary Foundation","doi-asserted-by":"publisher","award":["Grace Glaum Professorship"],"award-info":[{"award-number":["Grace Glaum Professorship"]}],"id":[{"id":"10.13039\/100012260","id-type":"DOI","asserted-by":"publisher"}]},{"name":"McCaig Institute"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Osteoarthritis (OA) is a chronic debilitating disease impacting a significant percentage of the global population. While there are numerous surgical and non-invasive interventions that can postpone joint replacement, there are no current treatments which can reverse the joint damage occurring during the pathogenesis of the disease. While many groups are investigating the use of stem cell therapies in the treatment of OA, we still don\u2019t have a clear understanding of the role of these cells in the body, including heterogeneity of tissue resident adult mesenchymal progenitor cells (MPCs).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In the current study, we examined MPCs from the synovium and individuals with or without a traumatic knee joint injury and explored the chondrogenic differentiation capacity of these MPCs in vitro and in vivo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found that there is heterogeneity of MPCs with the adult synovium and distinct sub-populations of MPCs and the abundancy of these sub-populations change with joint injury. Furthermore, only some of these sub-populations have the ability to effect cartilage repair in vivo. Using an unbiased proteomics approach, we were able to identify cell surface markers that identify this pro-chondrogenic MPC population in normal and injured joints, specifically CD82<jats:sup>Low<\/jats:sup>CD59<jats:sup>+<\/jats:sup> synovial MPCs have robust cartilage regenerative properties in vivo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The results of this study clearly show that cells within the adult human joint can impact cartilage repair and that these sub-populations exist within joints that have undergone a traumatic joint injury. Therefore, these populations can be exploited for the treatment of cartilage injuries and OA in future clinical trials.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13287-023-03396-3","type":"journal-article","created":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T16:01:39Z","timestamp":1687708899000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mesenchymal progenitor cells from non-inflamed versus inflamed synovium post-ACL injury present with distinct phenotypes and cartilage regeneration capacity"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2576-4504","authenticated-orcid":false,"given":"Roman J.","family":"Krawetz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Larijani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica May","family":"Corpuz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Ninkovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nabangshu","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Mohtadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Rezansoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Dufour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,6,25]]},"reference":[{"issue":"1","key":"3396_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nrrheum.2010.196","volume":"7","author":"M Kapoor","year":"2011","unstructured":"Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier J-P, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7(1):33\u201342.","journal-title":"Nat Rev Rheumatol"},{"issue":"1","key":"3396_CR2","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13075-017-1229-9","volume":"19","author":"A Mathiessen","year":"2017","unstructured":"Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Res Ther. 2017;19(1):18. https:\/\/doi.org\/10.1186\/s13075-017-1229-9.","journal-title":"Arthritis Res Ther"},{"key":"3396_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep23076","volume":"6","author":"J Mak","year":"2016","unstructured":"Mak J, Jablonski CL, Leonard CA, Dunn JF, Raharjo E, Matyas JR, et al. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model. Sci Rep. 2016;6:1\u201312.","journal-title":"Sci Rep"},{"issue":"11","key":"3396_CR4","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.1002\/art.34626","volume":"64","author":"M ter Huurne","year":"2012","unstructured":"ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, et al. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum. 2012;64(11):3604\u201313.","journal-title":"Arthritis Rheum"},{"issue":"8","key":"3396_CR5","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1002\/sctm.18-0183","volume":"8","author":"J Chahal","year":"2019","unstructured":"Chahal J, G\u00f3mez-Aristiz\u00e1bal A, Shestopaloff K, Bhatt S, Chaboureau A, Fazio A, et al. Bone marrow mesenchymal stromal cell treatment in patients with osteoarthritis results in overall improvement in pain and symptoms and reduces synovial inflammation. Stem Cells Transl Med. 2019;8(8):746\u201357.","journal-title":"Stem Cells Transl Med"},{"issue":"8","key":"3396_CR6","doi-asserted-by":"publisher","first-page":"e0221317","DOI":"10.1371\/journal.pone.0221317","volume":"14","author":"C Magri","year":"2019","unstructured":"Magri C, Schramme M, Febre M, Cauvin E, Labadie F, Saulnier N, et al. Comparison of efficacy and safety of single versus repeated intra-articular injection of allogeneic neonatal mesenchymal stem cells for treatment of osteoarthritis of the metacarpophalangeal\/metatarsophalangeal joint in horses: a clinical pilot study. PLoS. 2019;14(8):e0221317. https:\/\/doi.org\/10.1371\/journal.pone.0221317.","journal-title":"PLoS"},{"issue":"6","key":"3396_CR7","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.joca.2018.02.906","volume":"26","author":"DS Jevotovsky","year":"2018","unstructured":"Jevotovsky DS, Alfonso AR, Einhorn TA, Chiu ES. Osteoarthritis and stem cell therapy in humans: a systematic review. Osteoarthr Cartil. 2018;26(6):711\u201329.","journal-title":"Osteoarthr Cartil"},{"issue":"3","key":"3396_CR8","doi-asserted-by":"publisher","first-page":"215","DOI":"10.2174\/1574888X12666170915120620","volume":"13","author":"A Borakati","year":"2018","unstructured":"Borakati A, Mafi R, Mafi P, Khan WS. A systematic review and meta-analysis of clinical trials of mesenchymal stem cell therapy for cartilage repair. Curr Stem Cell Res Ther. 2018;13(3):215\u201325.","journal-title":"Curr Stem Cell Res Ther"},{"key":"3396_CR9","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.mad.2015.05.005","volume":"149","author":"AO Masson","year":"2015","unstructured":"Masson AO, Hess R, O\u2019Brien K, Bertram KL, Tailor P, Irvine E, et al. Increased levels of p21((CIP1\/WAF1)) correlate with decreased chondrogenic differentiation potential in synovial membrane progenitor cells. Mech Ageing Dev. 2015;149:31\u201340.","journal-title":"Mech Ageing Dev"},{"issue":"1","key":"3396_CR10","first-page":"1","volume":"13","author":"A Fichadiya","year":"2016","unstructured":"Fichadiya A, Bertram KL, Ren G, Yates RM, Krawetz RJ. Characterizing heterogeneity in the response of synovial mesenchymal progenitor cells to synovial macrophages in normal individuals and patients with osteoarthritis. J Inflamm (United Kingdom). 2016;13(1):1\u201311.","journal-title":"J Inflamm (United Kingdom)."},{"issue":"10","key":"3396_CR11","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1002\/stem.1477","volume":"31","author":"Q Harris","year":"2013","unstructured":"Harris Q, Seto J, O\u2019Brien K, Lee PS, Kondo C, Heard BJ, et al. Monocyte chemotactic protein-1 inhibits chondrogenesis of synovial mesenchymal progenitor cells: an in vitro study. Stem Cells. 2013;31(10):2253\u201365. https:\/\/doi.org\/10.1002\/stem.1477.","journal-title":"Stem Cells"},{"key":"3396_CR12","doi-asserted-by":"crossref","unstructured":"Krawetz RJ, Wu YE, Martin L, Rattner JB, Matyas JR, Hart DA. Synovial Fluid Progenitors Expressing CD90+ from Normal but Not Osteoarthritic Joints Undergo Chondrogenic Differentiation without Micro-Mass Culture. PLoS One. 2012;7(8):e43616.","DOI":"10.1371\/journal.pone.0043616"},{"issue":"1","key":"3396_CR13","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/s12891-019-2495-2","volume":"20","author":"A Affan","year":"2019","unstructured":"Affan A, Al-Jezani N, Railton P, Powell JN, Krawetz RJ. Multiple mesenchymal progenitor cell subtypes with distinct functional potential are present within the intimal layer of the hip synovium. BMC Musculoskelet Disord. 2019;20(1):125.","journal-title":"BMC Musculoskelet Disord"},{"issue":"5","key":"3396_CR14","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/s41419-022-04919-1","volume":"13","author":"RJ Krawetz","year":"2022","unstructured":"Krawetz RJ, Wu YE, Bertram KL, Shonak A, Masson AO, Ren G, et al. Synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity. Cell Death Dis. 2022;13(5):470.","journal-title":"Cell Death Dis"},{"issue":"5","key":"3396_CR15","doi-asserted-by":"publisher","first-page":"721","DOI":"10.2106\/00004623-199605000-00012","volume":"78","author":"EB Hunziker","year":"1996","unstructured":"Hunziker EB, Rosenberg LC. Repair of partial-thickness defects in articular cartilage: cell recruitment from the synovial membrane. J Bone Joint Surg Am. 1996;78(5):721\u201333.","journal-title":"J Bone Joint Surg Am"},{"issue":"1","key":"3396_CR16","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1053\/joca.2000.0346","volume":"9","author":"EB Hunziker","year":"2001","unstructured":"Hunziker EB. Growth-factor-induced healing of partial-thickness defects in adult articular cartilage. Osteoarthr Cartil. 2001;9(1):22\u201332.","journal-title":"Osteoarthr Cartil"},{"issue":"2","key":"3396_CR17","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.yexcr.2015.03.015","volume":"333","author":"WJ Lee","year":"2015","unstructured":"Lee WJ, Hah YS, Ock SA, Lee JH, Jeon RH, Park JS, et al. Cell source-dependent in vivo immunosuppressive properties of mesenchymal stem cells derived from the bone marrow and synovial fluid of minipigs. Exp Cell Res. 2015;333(2):273\u201388.","journal-title":"Exp Cell Res"},{"key":"3396_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00005-008-0001-x","volume":"56","author":"SA Patel","year":"2008","unstructured":"Patel SA, Sherman L, Munoz J, Rameshwar P. Immunological properties of mesenchymal stem cells and clinical implications. Arch Immunol Ther Exp. 2008;56:1\u20138.","journal-title":"Arch Immunol Ther Exp"},{"issue":"6","key":"3396_CR19","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.stem.2019.11.004","volume":"25","author":"RW Scott","year":"2019","unstructured":"Scott RW, Arostegui M, Schweitzer R, Rossi FMV, Underhill TM. Hic1 defines quiescent mesenchymal progenitor subpopulations with distinct functions and fates in skeletal muscle regeneration. Cell Stem Cell. 2019;25(6):797-813.e9.","journal-title":"Cell Stem Cell"},{"issue":"1","key":"3396_CR20","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13075-015-0634-1","volume":"17","author":"C De Bari","year":"2015","unstructured":"De Bari C. Are mesenchymal stem cells in rheumatoid arthritis the good or bad guys? Arthritis Res Ther. 2015;17(1):113.","journal-title":"Arthritis Res Ther"},{"key":"3396_CR21","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.3389\/fimmu.2019.01482","volume":"10","author":"S Sayegh","year":"2019","unstructured":"Sayegh S, El AO, Diallo K, Rauwel B, Degbo\u00e9 Y, Cavaignac E, et al. Rheumatoid synovial fluids regulate the immunomodulatory potential of adipose-derived mesenchymal stem cells through a TNF\/NF-\u03baB-dependent mechanism. Front Immunol. 2019;10:1482.","journal-title":"Front Immunol"},{"key":"3396_CR22","doi-asserted-by":"crossref","unstructured":"Cif\u00f9 A, Domenis R, Pozzi-Mucelli M, Di Benedetto P, Causero A, Moretti M, et al. The exposure to osteoarthritic synovial fluid enhances the immunomodulatory profile of adipose mesenchymal stem cell secretome. Stem Cells Int. 2020;2020.","DOI":"10.1155\/2020\/4058760"},{"issue":"5","key":"3396_CR23","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1002\/art.30234","volume":"63","author":"TB Kurth","year":"2011","unstructured":"Kurth TB, Dell\u2019accio F, Crouch V, Augello A, Sharpe PT, De Bari C. Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo. Arthritis Rheum. 2011;63(5):1289\u2013300. https:\/\/doi.org\/10.1002\/art.30234.","journal-title":"Arthritis Rheum"},{"issue":"1","key":"3396_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12891-020-03363-6","volume":"21","author":"AO Masson","year":"2020","unstructured":"Masson AO, Krawetz RJ. Understanding cartilage protection in OA and injury: a spectrum of possibilities. BMC Musculoskelet Disord. 2020;21(1):1\u201311.","journal-title":"BMC Musculoskelet Disord"},{"issue":"4","key":"3396_CR25","doi-asserted-by":"publisher","first-page":"774","DOI":"10.3390\/ijms18040774","volume":"18","author":"K O\u2019Brien","year":"2017","unstructured":"O\u2019Brien K, Tailor P, Leonard C, DiFrancesco L, Hart D, Matyas J, et al. Enumeration and localization of mesenchymal progenitor cells and macrophages in synovium from normal individuals and patients with pre-osteoarthritis or clinically diagnosed osteoarthritis. Int J Mol Sci. 2017;18(4):774.","journal-title":"Int J Mol Sci"},{"issue":"5","key":"3396_CR26","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/j.mri.2015.01.001","volume":"33","author":"J Mak","year":"2015","unstructured":"Mak J, Leonard C, Foniok T, Rushforth D, Dunn JF, Krawetz R. Evaluating endogenous repair of focal cartilage defects in C57BL\/6 and MRL\/MpJ mice using 9.4T magnetic resonance imaging: a pilot study. Magn Reson Imaging. 2015;33(5):690\u20134.","journal-title":"Magn Reson Imaging"},{"key":"3396_CR27","doi-asserted-by":"publisher","DOI":"10.1177\/1947603519876348","author":"CL Jablonski","year":"2021","unstructured":"Jablonski CLCL, Besler BABA, Ali J, Krawetz RJRJ. p21\u2212\/\u2212 Mice exhibit spontaneous articular cartilage regeneration post-injury. Cartilage. 2021. https:\/\/doi.org\/10.1177\/1947603519876348.","journal-title":"Cartilage"},{"issue":"12","key":"3396_CR28","doi-asserted-by":"publisher","first-page":"2561","DOI":"10.1002\/jor.24444","volume":"37","author":"CL Jablonski","year":"2019","unstructured":"Jablonski CL, Leonard C, Salo P, Krawetz RJ. CCL2 But Not CCR2 is required for spontaneous articular cartilage regeneration post-injury. J Orthop Res. 2019;37(12):2561\u201374.","journal-title":"J Orthop Res"},{"issue":"6","key":"3396_CR29","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.joca.2008.11.003","volume":"17","author":"NM Eltawil","year":"2009","unstructured":"Eltawil NM, De Bari C, Achan P, Pitzalis C, Dellaccio F. A novel in vivo murine model of cartilage regeneration. Age and strain-dependent outcome after joint surface injury. Osteoarthr Cartil. 2009;17(6):695\u2013704.","journal-title":"Osteoarthr Cartil"},{"issue":"4","key":"3396_CR30","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1111\/j.1365-2559.2006.02508.x","volume":"49","author":"V Krenn","year":"2006","unstructured":"Krenn V, Morawietz L, Burmester GR, Kinne RW, Mueller-Ladner U, Muller B, et al. Synovitis score: discrimination between chronic low-grade and high-grade synovitis. Histopathology. 2006;49(4):358\u201364.","journal-title":"Histopathology"},{"key":"3396_CR31","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1007\/s00441-022-03647-4","volume":"389(3)","author":"S Mudigonda","year":"2022","unstructured":"Mudigonda S, Shah S, Das N, Corpuz JM, Ninkovic N, Al-Jezani N, et al. Proteoglycan 4 is present within the dura mater and produced by mesenchymal progenitor cells. Cell Tissue Res. 2022;389:483\u201399.","journal-title":"Cell Tissue Res"},{"issue":"4","key":"3396_CR32","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1021\/pr101065j","volume":"10","author":"J Cox","year":"2011","unstructured":"Cox J, Neuhauser N, Michalski A, Scheltema RA, Olsen JV, Mann M. Andromeda: a peptide search engine integrated into the MaxQuant environment. J Proteome Res. 2011;10(4):1794\u2013805.","journal-title":"J Proteome Res"},{"issue":"12","key":"3396_CR33","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1038\/nbt.1511","volume":"26","author":"J Cox","year":"2008","unstructured":"Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized ppb-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008;26(12):1367\u201372.","journal-title":"Nat Biotechnol"},{"issue":"2","key":"3396_CR34","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nmeth.2811","volume":"11","author":"M Spitzer","year":"2014","unstructured":"Spitzer M, Wildenhain J, Rappsilber J, Tyers M. BoxPlotR: a web tool for generation of box plots. Nat Methods. 2014;11(2):121\u20132.","journal-title":"Nat Methods"},{"issue":"4","key":"3396_CR35","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1080\/14653240600855905","volume":"8","author":"M Dominici","year":"2006","unstructured":"Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DSS, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315\u20137.","journal-title":"Cytotherapy"},{"issue":"1","key":"3396_CR36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-07882-8","volume":"10","author":"Y Zhou","year":"2019","unstructured":"Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. 2019;10(1):1\u201310.","journal-title":"Nat Commun"},{"issue":"470","key":"3396_CR37","first-page":"514","volume":"42","author":"W Hunter","year":"1743","unstructured":"Hunter W. structure and diseases of articu\u00adlating cartilages. Philos Trans R Soc Lond. 1743;42(470):514\u201321.","journal-title":"Philos Trans R Soc Lond"},{"issue":"346","key":"3396_CR38","doi-asserted-by":"publisher","first-page":"346ra90","DOI":"10.1126\/scitranslmed.aad8335","volume":"8","author":"KM Heinemeier","year":"2016","unstructured":"Heinemeier KM, Schjerling P, Heinemeier J, M\u00f8ller MB, Krogsgaard MR, Grum-Schwensen T, et al. Radiocarbon dating reveals minimal collagen turnover in both healthy and osteoarthritic human cartilage. Sci Transl Med. 2016;8(346):346ra90. https:\/\/doi.org\/10.1126\/scitranslmed.aad8335.","journal-title":"Sci Transl Med"},{"issue":"6","key":"3396_CR39","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1053\/joca.2002.0801","volume":"10","author":"EB Hunziker","year":"2002","unstructured":"Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr Cartil. 2002;10(6):432\u201363.","journal-title":"Osteoarthr Cartil"},{"issue":"2","key":"3396_CR40","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s10067-009-1301-1","volume":"29","author":"JB Driban","year":"2010","unstructured":"Driban JB, Sitler MR, Barbe MF, Balasubramanian E. Is osteoarthritis a heterogeneous disease that can be stratified into subsets? Clin Rheumatol. 2010;29(2):123\u201331.","journal-title":"Clin Rheumatol"},{"issue":"9","key":"3396_CR41","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1016\/j.joca.2017.05.012","volume":"25","author":"KM Larson","year":"2017","unstructured":"Larson KM, Zhang L, Badger GJ, Jay GD. Early genetic restoration of lubricin expression in transgenic mice mitigates chondrocyte peroxynitrite release and caspase-3 activation. Osteoarthr Cartil. 2017;25(9):1488\u201395.","journal-title":"Osteoarthr Cartil"},{"issue":"3","key":"3396_CR42","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s00167-011-1743-2","volume":"20","author":"FP Luyten","year":"2012","unstructured":"Luyten FP, Denti M, Filardo G, Kon E, Engebretsen L. Definition and classification of early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2012;20(3):401\u20136. https:\/\/doi.org\/10.1007\/s00167-011-1743-2.","journal-title":"Knee Surg Sports Traumatol Arthrosc"},{"key":"3396_CR43","unstructured":"THE IMPACT OF ARTHRITIS IN CANADA: TODAY AND OVER THE NEXT 30 YEARS. http:\/\/www.arthritisalliance.ca\/images\/PDF\/eng\/Initiatives\/20111022_2200_impact_of_arthritis.pdf"},{"issue":"10","key":"3396_CR44","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/nrrheum.2013.109","volume":"9","author":"F Barry","year":"2013","unstructured":"Barry F, Murphy M. Mesenchymal stem cells in joint disease and repair. Nat Rev Rheumatol. 2013;9(10):584\u201394.","journal-title":"Nat Rev Rheumatol"},{"key":"3396_CR45","doi-asserted-by":"publisher","first-page":"10865","DOI":"10.1038\/ncomms10865","volume":"7","author":"AJ Cote","year":"2016","unstructured":"Cote AJ, McLeod CM, Farrell MJ, McClanahan PD, Dunagin MC, Raj A, et al. Single-cell differences in matrix gene expression do not predict matrix deposition. Nat Commun. 2016;7:10865.","journal-title":"Nat Commun"},{"issue":"9","key":"3396_CR46","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1016\/j.joca.2014.07.002","volume":"22","author":"Y Yu","year":"2014","unstructured":"Yu Y, Zheng H, Buckwalter JA, Martin JA. Single cell sorting identifies progenitor cell population from full thickness bovine articular cartilage. Osteoarthr Cartil. 2014;22(9):1318\u201326.","journal-title":"Osteoarthr Cartil"},{"issue":"9","key":"3396_CR47","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1093\/rheumatology\/kep192","volume":"48","author":"A Karystinou","year":"2009","unstructured":"Karystinou A, Dell\u2019Accio F, Kurth TBA, Wackerhage H, Khan IM, Archer CW, et al. Distinct mesenchymal progenitor cell subsets in the adult human synovium. Rheumatology (Oxford). 2009;48(9):1057\u201364. https:\/\/doi.org\/10.1093\/rheumatology\/kep192.","journal-title":"Rheumatology (Oxford)"},{"issue":"3","key":"3396_CR48","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3390\/genes9030159","volume":"9","author":"MC Manara","year":"2018","unstructured":"Manara MC, Pasello M, Scotlandi K. CD99: a cell surface protein with an oncojanus role in tumors. Genes (Basel). 2018;9(3):159.","journal-title":"Genes (Basel)"},{"issue":"1","key":"3396_CR49","doi-asserted-by":"publisher","first-page":"e171","DOI":"10.1002\/term.2329","volume":"12","author":"GA Martens","year":"2018","unstructured":"Martens GA, De Punt V, Stang\u00e9 G. CD99 as surface anchor for human islet endocrine cell purification. J Tissue Eng Regen Med. 2018;12(1):e171\u20136.","journal-title":"J Tissue Eng Regen Med"},{"issue":"1","key":"3396_CR50","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s12079-017-0445-z","volume":"12","author":"M Pasello","year":"2018","unstructured":"Pasello M, Manara MC, Scotlandi K. CD99 at the crossroads of physiology and pathology. J Cell Commun Signal. 2018;12(1):55\u201368.","journal-title":"J Cell Commun Signal"},{"issue":"5","key":"3396_CR51","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1002\/jbmr.2141","volume":"29","author":"M Sciandra","year":"2014","unstructured":"Sciandra M, Marino MT, Manara MC, Guerzoni C, Grano M, Oranger A, et al. CD99 drives terminal differentiation of osteosarcoma cells by acting as a spatial regulator of ERK 1\/2. J Bone Miner Res. 2014;29(5):1295\u2013309.","journal-title":"J Bone Miner Res"},{"issue":"1","key":"3396_CR52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13287-017-0532-3","volume":"8","author":"Z Husak","year":"2017","unstructured":"Husak Z, Dworzak MN. Chronic stress induces CD99, suppresses autophagy, and affects spontaneous adipogenesis in human bone marrow stromal cells. Stem Cell Res Ther. 2017;8(1):1\u201313.","journal-title":"Stem Cell Res Ther"},{"issue":"5","key":"3396_CR53","first-page":"304","volume":"50","author":"P Otte","year":"1991","unstructured":"Otte P. Basic cell metabolism of articular cartilage. Manometric studies Z Rheumatol. 1991;50(5):304\u201312.","journal-title":"Manometric studies Z Rheumatol"},{"issue":"4","key":"3396_CR54","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1002\/(SICI)1521-4141(199804)28:04<1125::AID-IMMU1125>3.0.CO;2-C","volume":"28","author":"N Shibagaki","year":"1998","unstructured":"Shibagaki N, Hanada KI, Yamaguchi S, Yamashita H, Shimada S, Hamada H. Functional analysis of CD82 in the early phase of T cell activation: Roles in cell adhesion and signal transduction. Eur J Immunol. 1998;28(4):1125\u201333.","journal-title":"Eur J Immunol"},{"issue":"4","key":"3396_CR55","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1007\/s00428-008-0590-0","volume":"452","author":"C Protzel","year":"2008","unstructured":"Protzel C, Kakies C, Kleist B, Poetsch M, Giebel J. Down-regulation of the metastasis suppressor protein KAI1\/CD82 correlates with occurrence of metastasis, prognosis and presence of HPV DNA in human penile squamous cell carcinoma. Virchows Arch. 2008;452(4):369\u201375.","journal-title":"Virchows Arch"},{"issue":"12","key":"3396_CR56","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.molmed.2005.10.002","volume":"11","author":"H Tonoli","year":"2005","unstructured":"Tonoli H, Barrett JC. CD82 metastasis suppressor gene: a potential target for new therapeutics? Trends Mol Med. 2005;11(12):563\u201370.","journal-title":"Trends Mol Med"},{"issue":"4","key":"3396_CR57","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.stem.2016.01.013","volume":"18","author":"J Hur","year":"2016","unstructured":"Hur J, Choi JI, Lee H, Nham P, Kim TW, Chae CW, et al. CD82\/KAI1 maintains the dormancy of long-term hematopoietic stem cells through interaction with DARC-expressing macrophages. Cell Stem Cell. 2016;18(4):508\u201321.","journal-title":"Cell Stem Cell"},{"issue":"1","key":"3396_CR58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13395-020-00252-3","volume":"10","author":"A Hall","year":"2020","unstructured":"Hall A, Fontelonga T, Wright A, Bugda Gwilt K, Widrick J, Pasut A, et al. Tetraspanin CD82 is necessary for muscle stem cell activation and supports dystrophic muscle function. Skelet Muscle. 2020;10(1):1\u201316.","journal-title":"Skelet Muscle"},{"issue":"1","key":"3396_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13045-021-01147-6","volume":"14","author":"JW Lee","year":"2021","unstructured":"Lee JW, Hur J, Kwon YW, Chae CW, Choi JI, Hwang I, et al. KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state. J Hematol Oncol. 2021;14(1):1\u201321.","journal-title":"J Hematol Oncol"},{"key":"3396_CR60","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.bone.2016.01.019","volume":"85","author":"M Rahmati","year":"2016","unstructured":"Rahmati M, Mobasheri A, Mozafari M. Inflammatory mediators in osteoarthritis: a critical review of the state-of-the-art, current prospects, and future challenges. Bone. 2016;85:81\u201390.","journal-title":"Bone"},{"issue":"11","key":"3396_CR61","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/nrrheum.2010.159","volume":"6","author":"J Sellam","year":"2010","unstructured":"Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010;6(11):625\u201335.","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"3396_CR62","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1136\/annrheumdis-2014-205894","volume":"75","author":"I Atukorala","year":"2016","unstructured":"Atukorala I, Kwoh CK, Guermazi A, Roemer FW, Boudreau RM, Hannon MJ, et al. Synovitis in knee osteoarthritis: a precursor of disease? Ann Rheum Dis. 2016;75(2):390\u20135. https:\/\/doi.org\/10.1136\/annrheumdis-2014-205894.","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"3396_CR63","first-page":"305","volume":"13","author":"M Maio","year":"1998","unstructured":"Maio M, Brasoveanu LI, Coral S, Sigalotti L, Lamaj E, Gasparollo A, et al. Structure, distribution, and functional role of protectin (CD59) in complement-susceptibility and in immunotherapy of human malignancies (Review). Int J Oncol. 1998;13(2):305\u201318.","journal-title":"Int J Oncol"},{"key":"3396_CR64","doi-asserted-by":"publisher","first-page":"10587","DOI":"10.1038\/ncomms10587","volume":"7","author":"M Serna","year":"2016","unstructured":"Serna M, Giles JL, Morgan BP, Bubeck D. Structural basis of complement membrane attack complex formation. Nat Commun. 2016;7:10587.","journal-title":"Nat Commun"},{"issue":"3","key":"3396_CR65","doi-asserted-by":"publisher","first-page":"326","DOI":"10.15283\/ijsc19157","volume":"13","author":"P Yadav","year":"2020","unstructured":"Yadav P, Vats R, Bano A, Bhardwaj R. Hematopoietic stem cells culture, expansion and differentiation: an insight into variable and available media. Int J Stem Cells. 2020;13(3):326\u201334.","journal-title":"Int J Stem Cells"},{"issue":"3","key":"3396_CR66","doi-asserted-by":"publisher","first-page":"e60461","DOI":"10.1371\/journal.pone.0060461","volume":"8","author":"MA Soland","year":"2013","unstructured":"Soland MA, Bego M, Colletti E, Zanjani ED, St. Jeor S, Porada CD, et al. Mesenchymal stem cells engineered to inhibit complement-mediated damage. PLoS ONE. 2013;8(3):e60461.","journal-title":"PLoS ONE"},{"key":"3396_CR67","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.3389\/fimmu.2019.02249","volume":"10","author":"C Gavin","year":"2019","unstructured":"Gavin C, Meinke S, Heldring N, Heck KA, Achour A, Iacobaeus E, et al. The complement system is essential for the phagocytosis of mesenchymal stromal cells by monocytes. Front Immunol. 2019;10:2249.","journal-title":"Front Immunol"},{"key":"3396_CR68","doi-asserted-by":"publisher","unstructured":"Liu-Bryan R. Synovium and the innate inflammatory network in osteoarthritis progression. Curr Rheumatol Rep 2013 May 21 [cited 2019 Jan 10];15(5):323. Available from: http:\/\/link.springer.com\/https:\/\/doi.org\/10.1007\/s11926-013-0323-5","DOI":"10.1007\/s11926-013-0323-5"},{"key":"3396_CR69","doi-asserted-by":"publisher","first-page":"170815","DOI":"10.1016\/j.peptides.2022.170815","volume":"154","author":"N Sch\u00e4fer","year":"2022","unstructured":"Sch\u00e4fer N, Gr\u00e4ssel S. Involvement of complement peptides C3a and C5a in osteoarthritis pathology. Peptides. 2022;154:170815.","journal-title":"Peptides"},{"key":"3396_CR70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep12798","volume":"5","author":"X Bai","year":"2015","unstructured":"Bai X, Wang Y, Man L, Zhang Q, Sun C, Hu W, et al. CD59 mediates cartilage patterning during spontaneous tail regeneration. Sci Rep. 2015;5:1\u201314.","journal-title":"Sci Rep"},{"issue":"3","key":"3396_CR71","doi-asserted-by":"publisher","first-page":"e17878","DOI":"10.1371\/journal.pone.0017878","volume":"6","author":"Y Wang","year":"2011","unstructured":"Wang Y, Wang R, Jiang S, Zhou W, Liu Y, Wang Y, et al. Gecko CD59 is implicated in proximodistal identity during tail regeneration. PLoS ONE. 2011;6(3):e17878.","journal-title":"PLoS ONE"},{"issue":"1","key":"3396_CR72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-61734-4","volume":"10","author":"R Griffiths","year":"2020","unstructured":"Griffiths R, Woods S, Cheng A, Wang P, Griffiths-Jones S, Ronshaugen M, et al. The transcription factor-microRNA regulatory network during hESC-chondrogenesis. Sci Rep. 2020;10(1):1\u201316.","journal-title":"Sci Rep"},{"issue":"11","key":"3396_CR73","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1136\/annrheumdis-2018-212954","volume":"77","author":"E Neumann","year":"2018","unstructured":"Neumann E, Schwarz MC, Hasseli R, H\u00fclser ML, Classen S, Sauerbier M, et al. Tetraspanin CD82 affects migration, attachment and invasion of rheumatoid arthritis synovial fibroblasts. Ann Rheum Dis. 2018;77(11):1619\u201326.","journal-title":"Ann Rheum Dis"}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-023-03396-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-023-03396-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-023-03396-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T16:02:08Z","timestamp":1687708928000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-023-03396-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,25]]},"references-count":73,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["3396"],"URL":"https:\/\/doi.org\/10.1186\/s13287-023-03396-3","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,25]]},"assertion":[{"value":"24 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 June 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Human: Informed consent to participate was obtained by written agreement. The study protocol was approved by the University of Calgary Research Ethics Board (University of Calgary ethics # REB16-1262, Title: Collection of Synovial Fluid and Tissues During Arthroscopic Knee Surgery, Approval Date: August 12, 2016, Approval #: N\/A). The study adhered to the Declaration of Helsinki. Animal: This study was carried out in accordance with the recommendations in the Canadian Council on Animal Care Guidelines. Animal protocols and surgical procedures were approved by the University of Calgary Animal Care Committee (Ethics # AC20-0042, Title: Stem cell tracking in mouse knee joints, Approval Date: May 25, 2020, Approval #: N\/A). Our reporting adheres to the ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"168"}}