CAMP-dependent protein kinase in chondrocyte cultures: Holoenzyme activation, phosphorylation of cellular proteins, effects of NSAIDs and possible role in proteoglycan synthesis

Abstract

R ECENT EVIDENCE showed that chondrocytes treated in culture with nonsteroidal antiinflammatory drugs (NSAIDs) exhibited reduced eicosanoid production, which was coupled to reduced intracellular accumulation of cyclic adenosine monophosphate (CAMP).’ Typically, NSAIDs have variable effects on cartilage proteoglycan and collagen synthesis and catabolism.2*3 Some NSAIDs are known to stimulate proteoglycan synthesis. These include sulindac sulfide4 and benoxaprofen5 However, the majority, including fenoprofen4 ibuprofen4 indomethacin,2T6*7 phenylbutazone,8 salicylates,7~9~‘0 and tolmetin,” suppress proteoglycan synthesis. Piroxicam may enhance proteolycan synthesisI or be without effect 12,13 the same can be said of the effect of tiaprdfenic acid2 and in some cases, indomethatin and sulindac sulfoxide.4 Many of these results come from studies conducted on articular cartilage explant culturesI or on cultured chondrocytes’2q’3 where a concentration range of NSAIDs can be tested readily. A recent review has appeared on this subject.” Two types of CAMP-dependent protein kinase (cAMPPk), type 1 and type 2, resolved by differential elution from diethylaminoethylcellulose (DEAE-cellulose), have been shown to