{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T04:09:16Z","timestamp":1783742956373,"version":"3.55.0"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T00:00:00Z","timestamp":1491350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Stem Cell Network"},{"name":"Alberta Innovates Health Solutions"},{"DOI":"10.13039\/501100000038","name":"NSERC","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"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is a degenerative disorder characterized by chondrocyte apoptosis and degeneration of articular cartilage resulting in loss of mobility and pain. Inflammation plays a key role in the development and progression of OA both on the side of apoptosis and repair, while its exact role in pathogenesis has yet to be fully elucidated. Few studies have examined the cellular composition (inflammatory cells and\/or progenitor cells) in the synovium of patients with pre-OA (asymptomatic with cartilage damage). Therefore, in the current study, mesenchymal progenitor cells (MPCs) and macrophages were enumerated within normal, pre-OA and OA synovium. No differences were observed between MPCs in normal vs. pre-OA, however, fewer macrophages were observed in pre-OA vs. normal synovium. Osteoarthritic synovium contained greater numbers of both MPCs and macrophages. Interestingly, the localization of MPCs and macrophages was affected by disease severity. In normal and pre-OA synovium, MPCs and macrophages co-localized, while in OA synovium, MPCs and macrophage populations were spatially distinct. Examining the cellular interactions between MPCs and macrophages in synovium may be essential for understanding the role of these cells in the onset and\/or pathogenesis of the disease. This study has provided a first step by examining these cell types both spatially and temporally (e.g., disease severity). Further cellular and molecular studies will be needed to determine the functions of these cells in the context of disease and in relation to each other and the joint as a whole.<\/jats:p>","DOI":"10.3390\/ijms18040774","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T10:33:01Z","timestamp":1491388381000},"page":"774","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Enumeration and Localization of Mesenchymal Progenitor Cells and Macrophages in Synovium from Normal Individuals and Patients with Pre-Osteoarthritis or Clinically Diagnosed Osteoarthritis"],"prefix":"10.3390","volume":"18","author":[{"given":"Kate","family":"O\u2019Brien","sequence":"first","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB T2N4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Tailor","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB T2N4N1, Canada"},{"name":"Department Cell Biology and Anatomy, University of Calgary, Calgary, AB T2N4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Leonard","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB T2N4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"DiFrancesco","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of Calgary, Calgary, AB T2N4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hart","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB T2N4N1, Canada"},{"name":"Department of Surgery, University of Calgary, Calgary, AB T2N4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Matyas","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB T2N4N1, Canada"},{"name":"Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB T2N4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Frank","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB T2N4N1, Canada"},{"name":"Department of Surgery, University of Calgary, Calgary, AB T2N4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Krawetz","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB T2N4N1, Canada"},{"name":"Department Cell Biology and Anatomy, University of Calgary, Calgary, AB T2N4N1, Canada"},{"name":"Department of Surgery, University of Calgary, Calgary, AB T2N4N1, Canada"},{"name":"The D-BOARD European Consortium for Biomarker Discovery, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1056\/NEJMcp071112","article-title":"Clinical practice. Osteoarthritis of the hip","volume":"357","author":"Lane","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1056\/NEJMcp051726","article-title":"Clinical practice. Osteoarthritis of the knee","volume":"354","author":"Felson","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1002\/jor.20370","article-title":"Periarticular ligament changes following ACL\/MCL transection in an ovine stifle joint model of osteoarthritis","volume":"25","author":"Funakoshi","year":"2007","journal-title":"J. Orthop. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"35","DOI":"10.7748\/ns.24.1.35.s50","article-title":"Osteoarthritis: Pathogenesis, clinical features and management","volume":"24","author":"Walker","year":"2009","journal-title":"Nurs. Stand."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.bone.2012.02.012","article-title":"The role of synovitis in osteoarthritis pathogenesis","volume":"51","author":"Scanzello","year":"2012","journal-title":"Bone"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S1063-4584(05)80017-2","article-title":"Osteoarthritis of the knee after injury to the anterior cruciate ligament or meniscus: The influence of time and age","volume":"3","author":"Roos","year":"1995","journal-title":"Osteoarthr. Cartil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/00001648-199903000-00013","article-title":"Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee","volume":"10","author":"Oliveria","year":"1999","journal-title":"Epidemiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/S0140-6736(14)60802-3","article-title":"Osteoarthritis","volume":"386","author":"Palmer","year":"2015","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.joca.2005.01.005","article-title":"Synovitis: A potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis\u2014Results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthritis and Cartilage\/OARS","volume":"13","author":"Ayral","year":"2005","journal-title":"Osteoarthr. Res. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nrrheum.2010.159","article-title":"The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis","volume":"6","author":"Sellam","year":"2010","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1002\/art.24312","article-title":"An ultrasonographic study of osteoarthritis of the hand: Synovitis and its relationship to structural pathology and symptoms","volume":"59","author":"Keen","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1302\/0301-620X.90B4.20284","article-title":"The assessment of early osteoarthritis","volume":"90","author":"Pollard","year":"2008","journal-title":"J. Bone Jt. Surg."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"100","DOI":"10.2174\/1874312901105010100","article-title":"The normal synovium","volume":"5","author":"Smith","year":"2011","journal-title":"Open Rheumatol. J."},{"key":"ref_15","first-page":"237","article-title":"The role of cytokines in osteoarthritis pathophysiology","volume":"39","author":"Fernandes","year":"2002","journal-title":"Biorheology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1002\/stem.1477","article-title":"Monocyte chemotactic protein-1 inhibits chondrogenesis of synovial mesenchymal progenitor cells: An in vitro study","volume":"31","author":"Harris","year":"2013","journal-title":"Stem Cells"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.joca.2014.05.021","article-title":"Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal stem cells via macrophage polarisation state","volume":"22","author":"Fahy","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12950-016-0120-9","article-title":"Characterizing heterogeneity in the response of synovial mesenchymal progenitor cells to synovial macrophages in normal individuals and patients with osteoarthritis","volume":"13","author":"Fichadiya","year":"2016","journal-title":"J. Inflamm. Lond."},{"key":"ref_19","first-page":"346ra90","article-title":"Radiocarbon dating reveals minimal collagen turnover in both healthy and osteoarthritic human cartilage","volume":"6","author":"Heinemeier","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3899\/jrheum.100614","article-title":"Quantification of cells expressing mesenchymal stem cell markers in healthy and osteoarthritic synovial membranes","volume":"38","author":"Blanco","year":"2011","journal-title":"J. Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/jor.22029","article-title":"Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis","volume":"30","author":"Sekiya","year":"2012","journal-title":"J. Orthop. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Krawetz, R.J., Wu, Y.E., Martin, L., Rattner, J.B., Matyas, J.R., and Hart, D.A. (2012). Synovial fluid progenitors expressing CD90+ from normal but not osteoarthritic joints undergo chondrogenic differentiation without micro-mass culture. PLoS ONE, 7.","DOI":"10.1371\/annotation\/ace75296-7ec7-4193-ac91-5d68cfe5073e"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/S1063-4584(03)00167-5","article-title":"Identification, quantification and isolation of mesenchymal progenitor cells from osteoarthritic synovium by fluorescence automated cell sorting","volume":"11","author":"Fickert","year":"2003","journal-title":"Osteoarthr. Cartil."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ogata, Y., Mabuchi, Y., Yoshida, M., Suto, E.G., Suzuki, N., Muneta, T., Sekiya, I., and Akazawa, C. (2015). Purified Human Synovium Mesenchymal Stem Cells as a Good Resource for Cartilage Regeneration. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129096"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1089\/ten.tea.2010.0346","article-title":"Bone marrow cells immunomagnetically selected for CD271+ antigen promote in vitro the repair of articular cartilage defects","volume":"17","author":"Blanco","year":"2011","journal-title":"Tissue Eng. Part A"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1002\/art.20203","article-title":"Enumeration and phenotypic characterization of synovial fluid multipotential mesenchymal progenitor cells in inflammatory and degenerative arthritis","volume":"50","author":"Jones","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1136\/ard.2003.013383","article-title":"Immunohistochemistry of normal human knee synovium: A quantitative study","volume":"63","author":"Singh","year":"2004","journal-title":"Ann. Rheum. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1136\/ard.2004.025270","article-title":"Synovial tissue inflammation in early and late osteoarthritis","volume":"64","author":"Benito","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R116","DOI":"10.1186\/ar4296","article-title":"Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation","volume":"15","author":"Alves","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/j.1365-2559.2006.02508.x","article-title":"Synovitis score: Discrimination between chronic low-grade and high-grade synovitis","volume":"49","author":"Krenn","year":"2006","journal-title":"Histopathology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/4\/774\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:32:00Z","timestamp":1760207520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/4\/774"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,5]]},"references-count":31,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,4]]}},"alternative-id":["ijms18040774"],"URL":"https:\/\/doi.org\/10.3390\/ijms18040774","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,5]]}}}