Immunohistochemical characterization of early and advanced knee osteoarthritis by NF‐κB and iNOS expression

This study was performed to determine the differences in grade of synovitis and expression of NF‐κB and iNOS in knee synovial membrane between early and advanced stage of osteoarthritis (OA). Thirty synovial membrane intra‐operative biopsies of patients (ten controls, ten with early and ten with advanced OA according to Kellgren–Lawrence radiological score) were immunohistochemically (NF‐κB and iNOS) and hystologically (Krenn synovitis score) analyzed and correlated to WOMAC clinical score and pain duration. Krenn synovitis score of patients with radiologically early OA was significantly higher than in patients with advanced OA (p < 0.001). NF‐κB expression in both synovial intima (p < 0.001) and subintima (p < 0.001) was also higher in early OA. iNOS expression in subintima was significantly higher in early than in advanced OA (p < 0.001), while in intima iNOS showed no statistical difference between groups (p = 0.07). The lymphocytic nodules, located in synovial subintima, were significantly higher in advanced OA when compared to early OA (p = 0.006) and the control group (p < 0.001). These results suggest that in early OA, there is a localized inflammation of the synovial membrane with high expression of NF‐κB and iNOS. In advanced OA, number of expressed factors is reduced, with the exception of intima cells that highly express iNOS, reflecting the ongoing localized inflammatory process of lower degree. In advanced OA, the density of the resident cells is reduced and lymphocytic nodules appear, confirming the important role of adaptive immunity in later OA stage. Clinical significance of this study is better understanding possibilities of preventive measures for synovitis and OA advancement. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1990–1997, 2017.