THE SUPERFICIAL LAYER OF HUMAN ARTICULAR-CARTILAGE IS MORE SUSCEPTIBLE TO INTERLEUKIN-1-INDUCED DAMAGE THAN THE DEEPER LAYERS

Objective. To compare the responses of chondrocytes from superficial a nd deep layers of normal human articular cartilage to interleukin-1 (I L-1) and IL-1 receptor antagonist protein (IRAP), and to evaluate the binding sites for IL-1 on these cells. Methods. Cartilage and chondroc ytes from superficial and deeper layers of human femoral condyles were cultured with and without IL-1 in the presence and absence of IRAP. T he effect of these agents on S-35-proteoglycan synthesis and catabolis m and production of stromelysin and tissue inhibitor of metalloprotein ases 1 (TIMP-1) were measured by biochemical and immunologic assays. R eceptor binding was evaluated using I-125-labeled IL-1. Results. IL-1 induced more severe inhibition of proteoglycan synthesis and a lower r atio of secreted TIMP-1:stromelysin in chondrocytes from superficial c artilage than those from deeper cartilage. IRAP blocked responses to I L-1 more effectively in chondrocytes from deep cartilage than those fr om superficial cartilage. Chondrocytes from the articular surface show ed approximately twice the number of high-affinity binding sites for I L-1 as did cells from deep cartilage. Conclusion. Chondrocytes from th e surface of articular cartilage show a greater vulnerability to the h armful effects of IL-1 and are less responsive to the potential therap eutic effects of IRAP than cells in the deeper layers of the tissue.