Increased level of cytokines and matrix metalloproteinases in osteoarthritic subchondral bone

Objective: The aim of this study was to investigate the expression of several cytokines, matrix metalloproteinases (MMPs), and tissue inhibitor of matrix metalloproteinases (TIMP)-1 in osteoarthritis (OA) and control sera and different joint tissues. Methods: Serum, synovial fluid, cartilage, synovial and subchondral bone tissues were examined in OA and control subjects. The protein level of tumor necrosis factor (TNF)-alpha, interleukin (IL)-lot, IL-8, IL-10 and MMP-2, MMP-3, MMPP-9, and TIMP-1 were measured by immunoanalysis. Results: Serum levels of TNF-alpha, MMP-3 and -9 were significantly higher in OA patients than in controls. Conversely, serum IL-10 was decreased in OA patients. CRP was elevated when compared to healthy controls and decreased significantly 6 months after the surgery. In contrast to control samples, OA cartilage and synovium revealed significantly higher MMP-2, MMP-3, -9 and IL-10. IL-1 alpha was significantly higher in OA cartilage and IL-8 in OA synovium. Interestingly, MMP-3, -9, TIMP-1 and all tested cytokines were up-regulated in OA subchondral bone. Discussion: This study demonstrates pro-inflammatory condition of OA pathology and supports the idea that vascularized subchondral region may increase the synthesis of cytokines and MMPs leading to degradation of adjacent cartilage. (c) 2007 Elsevier Ltd. All rights reserved.