The dysbalance of proteinase production and their inhibitors leads to destruction of tissues in many pathological processes. Recently it was shown that the expression of proteinases is regulated also by interactions of cells which is mediated by adhesive molecules. We wanted to find out whether this mechanism is involved also in the destruction of joints in osteoarthritis.
Cartilage, synovial and subchondral bone tissues, and synovial fluids were obtained from 23 joints after total endoprosthesis surgery. The solid tissues were extracted by TRIS buffer. The investigated protein concentrations were assessed immunochemicaly. In all specimens gelatinase A, gelatinase B, stromelysin-1, TIMP-1, soluble adhesive molecules sICAM-1 and sVCAM-1 and cytokines TNF-alpha and IL-8 were found. In cartilage and synovial fluid the proteolytic potential of metalloproteinases was balanced with high concentrations of their inhibitor TIMP-1 (259.4 +/- 105.2 pmol/g protein vs 2343.8 +/- 637.5 pmol/g protein in synovial fluid, p < 0.00001, and 178.9 +/- 175.7 pmol/g dry weight vs 647.2 +/- 561.3 pmol/g dry weight in cartilage, p < 0.001) but in synovial tissues and pathological subchondral bones was not (257.4 +/- 617.2 pmol/g dry weight vs 171.3 +/- 170.8 pmol/g dry weight in synovium, p = 0.61716, and 17.4 +/- 15.4 pmol/g dry weight 33.6 +/- 33.3 pmol/g dry tissue in pathological subchondral bone, p = 0.16705).
From correlation analysis ensues that the bond of ICAM-1 and VCAM-1 on chondrocytes with appropriate integrin ligands probably leads to up-regulation of gelatinase A and B and to down-regulation of TIMP-1. Moreover it is apparent that TNF-alpha up-regulates both investigated adhesive molecules followed and stromelysin-1 and TIMP-1.