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The addition of ATP, but not ADP or AMP, to the culture media of bovine nasal cartilage explants caused an acceleration in the rate of proteoglycan loss from the tissue. The ATP-stimulated loss of proteoglycan was not inhibited by the IL1-receptor antagonist protein, but was partially inhibited by the presence of ADP or AMP. The proteolytic events resulting from the presence of ATP were found to be similar to those following treatment with IL1, in that inhibitors of the cysteine-peptidase cathepsin B, serine-proteinases with trypsin-like specificity, and of some of the matrixins, could all prevent proteoglycan loss, which was mediated, at least in part, by the action of 'aggrecanase'. In contrast to its effects on nasal cartilage, ATP inhibited basal and stimulated proteoglycan release from articular cartilage. Both ADP and AMP had no effect on proteoglycan release in articular cartilage but enhanced the response to ATP when added concurrently. We conclude that extracellular ATP, probably acting via P2-purinoceptors, stimulates proteoglycan breakdown from bovine nasal cartilage and thus, may have a role in diseases which primarily involve destruction of non-articular cartilage. Extracellular ATP has, in contrast, a chondroprotective effect on bovine articular cartilage.

Original publication

DOI

10.1016/s0925-4439(97)00080-x

Type

Journal article

Journal

Biochim biophys acta

Publication Date

31/12/1997

Volume

1362

Pages

208 - 220

Keywords

Adenosine Diphosphate, Adenosine Monophosphate, Adenosine Triphosphate, Aggrecans, Animals, Cartilage, Cartilage, Articular, Cattle, Culture Techniques, Drosophila Proteins, Extracellular Matrix Proteins, Interleukin-1, Lectins, C-Type, Molecular Weight, Prostaglandins E, Protease Inhibitors, Proteoglycans, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ret, Receptor Protein-Tyrosine Kinases, Time Factors, Tumor Necrosis Factor-alpha