Proteoglycan breakdown from bovine nasal cartilage is increased, and from articular cartilage is decreased, by extracellular ATP

Abstract

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.

The role of purinergic signalling in the musculoskeletal system

“…ATP has been reported to inhibit cartilage formation in micromass cultures (Meyer et al, 2001), promote proteoglycan breakdown and glycosaminoglycan release in bovine nasal cartilage (Brown et al, 1997) and increase the production of inflammatory mediators, nitric oxide (NO) and PGE2 (Varani et al, 2008b). Furthermore, P2Y2…”

Immunolocalisation of P2X and P2Y nucleotide receptors in the rat nasal mucosa

“…In mammals the application of ATP and GTP to bimolecular lipid membranes modified with rat olfactory homogenates resulted in increased conductivity of the membrane in response to odorants (Vodyanoy and Vodyanoy 1987). Proteoglycan breakdown from bovine nasal cartilage is stimulated and accelerated by ATP in vitro using a process involving P2 purinoceptors (Brown et al 1997). The effects of ATP have been described in the catfish (Kang and Caprio 1995).…”

Purinergic signalling in the musculoskeletal system

“…Activation of the P2Y 1 receptor by ATP inhibited cartilage formation in micromass cultures of chick limb undifferentiated mesenchyme cells [311]. ATP was also reported to promote proteoglycan breakdown and glycosaminoglycan release in bovine nasal cartilage [312] and increase the production of inflammatory mediators, nitric oxide (NO) and PGE 2 [303]. Furthermore, in articular chondrocytes, stimulation of P2Y 2 receptors by ATP increased IL-1-mediated PGE 2 release [300] and induced a rapid rise in PGE 2 synthesis via an ERK1/2 and p38 MAPK-mediated activation of cytoplasmic PLA 2 [313].…”