Differential activation by cytokines of mitogen-activated protein kinases in bovine temporomandibular-joint disc cells

Temporomandibular disorders affect a significant proportion of the populati on. While their aetiology is not well defined, recent histological studies suggest that the majority are similar to the osteoarthritis seen in other j oints. Inflammatory cytokines such as interleukin-1 and tumour necrosis fac tor-alpha appear to be important in the cascade of events leading to joint destruction in osteoarthritis. Here, cells from the disc of bovine temporom andibular joint were used to examine the response to various cytokines in v itro. Disc cells were stimulated with interleukin-1 alpha, tumour necrosis factor-alpha, transforming growth factor-beta, platelet-derived growth fact or, and basic fibroblast growth factor. Their effects were monitored by ass essing the phosphorylation of selected signal-transduction intermediates us ing western blot. Mitogen-activated protein kinases (Erk 1, Erk 2) were rap idly phosphorylated by exposure to basic fibroblast growth factor, platelet -derived growth factor, and tumour necrosis factor-alpha, while interleukin -1 alpha. showed a weak response. Transforming growth factor-beta failed to activate these kinases. Examination of the effect of these cytokines on p3 8 (an intermediate in the stress-activated protein-kinase pathway) showed a n increase in phosphorylated p38 when stimulated with tumour necrosis facto r-alpha and interleukin-1 alpha. The amounts of phosphorylated signal trans ducer and activator of transcription-3 did not significantly increase when the cells were exposed to any of the cytokines. (C) 1999 Elsevier Science L td. All rights reserved.