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J Cell Physiol. 2006 Dec;209(3):845-53.

Purinergic pathway suppresses the release of .NO and stimulates proteoglycan synthesis in chondrocyte/agarose constructs subjected to dynamic compression.

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  • 1Medical Engineering Division, Department of Engineering, Queen Mary, University of London, Mile End Road, London, UK. t.t.chowdhury@qmul.ac.uk

Abstract

Mechanical loading plays a fundamental role in the physiological and pathological processes of articular cartilage. The application of dynamic compression to chondrocytes cultured in agarose, downregulates the release of nitric oxide (NO) and enhances cell proliferation and proteoglycan synthesis. We hypothesize that the observed metabolic changes in response to dynamic compression involve a purinergic signaling pathway. Chondrocyte/agarose constructs were subjected to dynamic compression (15%, 1 Hz, 48 h) in the presence of antagonists for the purinergic pathway. Gadolinium was used as a putative inhibitor of stretch-activated calcium ion channels including adenosine 5'-triphosphate (ATP) release channels; suramin was employed as a P2 receptor antagonist and apyrase was used to catalyze the hydrolysis of extracellular ATP. The data presented demonstrate that in the absence of the inhibitor, dynamic compression suppressed .NO release. Treatment with gadolinium and suramin caused a compression-induced upregulation of .NO release, a response abolished with apyrase. Compression-induced stimulation of cell proliferation was reversed with gadolinium, suramin, or apyrase. By contrast, compression-induced stimulation of proteoglycan synthesis was abolished under all treatment conditions. Thus, the purinergic pathway is important in suppressing the release of .NO and stimulation of proteoglycan synthesis. Indeed, high levels of .NO could trigger a downstream catabolic response and mediate the compression-induced inhibition of cell proliferation. The current study demonstrates for the first time the importance of a purinergic pathway in mediating the metabolic response to dynamic compression and suppressing an inflammatory effect.

(c) 2006 Wiley-Liss, Inc.

PMID:
16924659
[PubMed - indexed for MEDLINE]
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