Osteoarthritis (OA) is a debilitating joint disease affect primarily the elderly. The prevalence of symptomatic OA is higher in the knee joint, than in the ankle. As progressive cartilage degeneration seen in OA increased markedly during adult life, it is important to learn more about the mechanisms driving normal aging. An advantage of the proposed study using the ankle cartilage from human organ donor is the opportunity of documenting cartilage changes in a joint that rarely develops OA. Thin ankle cartilage could serve as an ideal model for studying normal aging processes which do not have impact of changes leading to disease. A significant finding of this study to data has been the establishment of a grading system for joints which cartilage has been taken so that the cartilages could be identified as normal or damaged distinguishing between normal (non pathologically progressive) aging process and pathologically progressive degeneration of cartilage. By eliminating from our studies cartilages with signs of OA, we intend to identify only those biochemical and/or molecular biological differences which are age-related. The uniqueness of this project is that we have unlimited access to human tissue. All ankle cartilages to be tested are from human organ donors collected through the Regional Organ Bank of Illinois within 24 hours of death. For the proposed studies we have chosen to investigate the role of one of the matrix metalloproteinase (MMP), MMP-8, in aging of human ankle cartilage from four age groups: 1) under 10 years old; 2) 20-40 years old; 3) 40-60 years old and 4) 60 and over years old. We have selected this proteinase because of its catalytic activity against both collagen and aggrecan, the major components of the extracellular matrix. Our preliminary data indicate that in relatively young adult ankle articular cartilage the expression of MMP-8 mRNA is negative or barely detectable, however this proteinase is highly up-regulated in OA cartilages from elderly patients. We hypothesize that with normal aging of ankle cartilage some modulation of MMP-8 expression and activity is taking place, but does not lead to accelerated catabolism of aggrecan and collagen. The overall goals of the proposed studies are 1) to define age-related changes in chondrocyte MMP-8 and 2) to study specific changes which the proteinase undergoes with age if cartilage degeneration is enhanced by exposure to catabolic mediator, interleukin-1, at concentrations effective in altering matrix steady state metabolism. Once the involvement of MMP-8 in normal aging of cartilage is better understood, the approaches presented here could prove most helpful in defining the role of MMP-8 in disease-related processes (long-term goal).
