1. Immunofluorescence Analysis of NF-kB and iNOS Expression in Different Cell Populations during Early and Advanced Knee Osteoarthritis
- Author
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Marko Ostojic, Violeta Soljic, Katarina Vukojević, and Ante Zevrnja
- Subjects
0301 basic medicine ,Male ,Fluorescent Antibody Technique ,Nitric Oxide Synthase Type II ,osteoarthritissynovitisinducible nitric oxide synthasenuclear factor kappa Bmacrophage ,Vimentin ,Stem cell marker ,Severity of Illness Index ,0302 clinical medicine ,Macrophage ,Biology (General) ,Spectroscopy ,biology ,CD68 ,Synovial Membrane ,NF-kappa B ,General Medicine ,Osteoarthritis, Knee ,Immunohistochemistry ,Computer Science Applications ,Chemistry ,medicine.anatomical_structure ,nuclear factor kappa B ,Female ,Blood vessel ,Adult ,QH301-705.5 ,macrophage ,Article ,Catalysis ,Inorganic Chemistry ,Andrology ,03 medical and health sciences ,Young Adult ,Synovitis ,medicine ,Humans ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,030203 arthritis & rheumatology ,business.industry ,Organic Chemistry ,inducible nitric oxide synthase ,medicine.disease ,Matrix Metalloproteinases ,osteoarthritis ,030104 developmental biology ,biology.protein ,Synovial membrane ,CD5 ,synovitis ,business ,Biomarkers - Abstract
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—NF-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–Lawrence 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 <, 0.001 and p <, 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 <, 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 <, 0.0001 and p <, 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 <, 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.
- Published
- 2021