{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T12:18:12Z","timestamp":1782562692967,"version":"3.54.5"},"reference-count":58,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Synovitis of the knee synovium is proven to be a precursor of knee osteoarthritis (OA), leading to a radiologically advanced stage of the disease. This study was conducted to elucidate the expression pattern of different inflammatory factors\u2014NF-kB, iNOS, and MMP-9 in a subpopulation of synovial cells. Thirty synovial membrane intra-operative biopsies of patients (ten controls, ten with early OA, and ten with advanced OA, according to the Kellgren\u2013Lawrence radiological score) were immunohistochemically stained for NF-kB, iNOS, and MMP9, and for different cell markers for macrophages, fibroblasts, leukocytes, lymphocytes, blood vessel endothelial cells, and blood vessel smooth muscle cells. The total number of CD68+\/NF-kB+ cells\/mm2 in the intima of early OA patients (median = 2359) was significantly higher compared to the total number of vimentin+\/Nf-kB+ cells\/mm2 (median = 1321) and LCA+\/NF-kB+ cells\/mm2 (median = 64) (p &lt; 0.001 and p &lt; 0.0001, respectively). The total number of LCA+\/NF-kB+ cells\/mm2 in the subintima of advanced OA patients (median = 2123) was significantly higher compared to the total number of vimentin+\/NF-kB+ cells\/mm2 (median = 14) and CD68+\/NF-kB+ cells\/mm2 (median = 29) (p &lt; 0.0001). The total number of CD68+\/iNOS+ cells\/mm2 in the intima of both early and advanced OA patients was significantly higher compared to the total number of vimentin+\/iNOS+ cells\/mm2 and LCA+\/iNOS+ cells\/mm2 (p &lt; 0.0001 and p &lt; 0.001, respectively). The total number of CD68+\/MMP-9+ cells\/mm2 in the intima of both early and advanced OA patients was significantly higher compared to the total number of vimentin+\/MMP-9+ cells\/mm2 and CD5+\/MMP-9+ cells\/mm2 (p &lt; 0.0001). Macrophages may have a leading role in OA progression through the NF-kB production of inflammatory factors (iNOS and MMP-9) in the intima, except in advanced OA, where leukocytes could have a dominant role through NF-kB production in subintima. The blocking of macrophageal and leukocyte NF-kB expression is a possible therapeutic target as a disease modifying drug.<\/jats:p>","DOI":"10.3390\/ijms22126461","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T10:27:07Z","timestamp":1623839227000},"page":"6461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Immunofluorescence Analysis of NF-kB and iNOS Expression in Different Cell Populations during Early and Advanced Knee Osteoarthritis"],"prefix":"10.3390","volume":"22","author":[{"given":"Marko","family":"Ostojic","sequence":"first","affiliation":[{"name":"Department of Orthopaedics and Traumatology, University Hospital Mostar, 88 000 Mostar, Bosnia and Herzegovina"},{"name":"Department of Anatomy, School of Medicine, University of Mostar, 88 000 Mostar, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ante","family":"Zevrnja","sequence":"additional","affiliation":[{"name":"Public Health Centre, First Responders Unit, 21 000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2182-2890","authenticated-orcid":false,"given":"Katarina","family":"Vukojevic","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Soltanska 2, 21 000 Split, Croatia"},{"name":"Department of Histology and Embryology, School of Medicine, University of Mostar, Kralja Petra Kresimira IV, 88 000 Mostar, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Soljic","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, School of Medicine, University of Mostar, Kralja Petra Kresimira IV, 88 000 Mostar, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: A disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1177\/1759720X12467868","article-title":"Role of inflammation in the pathogenesis of osteoarthritis: Latest findings and interpretations","volume":"5","author":"Sokolove","year":"2013","journal-title":"Ther. 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