Chondrocyte tumor necrosis factor receptors and focal loss of cartilage in osteoarthritis

Abstract

Osteoarthritis (OA) is characterized by focal loss of cartilage. Here we show for the first time that tumor necrosis factor (TNF) alpha can act on cartilage but only at specific sites where chondrocyte TNF alpha-receptor (R) expression is high. Cartilage explants from specified sites in the knee joints of both OA patients and non-arthritic (NA) subjects were cultured with and without TNF alpha for 14 days and cumulative glycosaminoglycan (GAG) release into the supernatant measured. p55 and p75 TNF-R expression was measured by flow cytometry on chondrocytes isolated from the same sites. Cartilage explants from different sites in knee joints from both OA patients and NA subjects varied in their susceptibility to TNF alpha. Overall, the proportion of samples that responded to TNF alpha was higher in cartilage taken from OA joints than cartilage from NA subjects. Variations in p55 and p75 TNF-R expression were found between chondrocytes from different sites. p55, but not p75 TNF-R, expression on chondrocytes was closely related to the susceptibility of explants from the same site to TNF alpha-induced GAG loss. It is considered that focal loss of cartilage will occur at sites where chondrocyte p55 TNF-R expression is high, if sufficient TNF alpha is present, and that these results identify a mechanism by which cytokine-mediated focal loss of cartilage may occur.