Mechanosensitive hyaluronan secretion: stimulus-response curves and role of transcription-translation-translocation in rabbit joints.

Abstract:

:Joint movement was recently shown to stimulate the secretion of the lubricant hyaluronan (HA); also, exercise therapy and intra-articular hyaluronan injections are used to treat moderate osteoarthritis. The present study quantifies the stimulus-response curves for HA secretion in vivo and reports a role of transcription-translation-translocation in the secretory response. After washing out endogenous HA from anaesthetized, cannulated rabbit knees, the joints were cycled passively at various frequencies and durations, with or without intra-articular inhibitors of protein synthesis and Golgi processing. Newly secreted HA was harvested for analysis after 5 h. Joints displayed graded, non-linear stimulus-response curves to both duration and frequency of movement; 1 min duration per 15 min or a frequency of 0.17 Hz raised HA secretion by 42-54%, while rapid (1.5 Hz) or prolonged cycling (9 min per 15 min) raised it by 110-130%. Movement-stimulated secretion and phorbol ester-stimulated secretion were partly inhibited by the translation inhibitor cycloheximide, by the transcription-translation inhibitors actinomycin D and puromycin and by the Golgi translocation inhibitor brefeldin A. There is thus a graded coupling between HA secretion and cyclic joint movement that depends partly on new protein synthesis. This is likely to be important for joint homeostasis, providing protection during repetitive cycling and potentially contributing to exercise therapy for osteoarthritis.

journal_name

Exp Physiol

journal_title

Experimental physiology

authors

Wann AK,Ingram KR,Coleman PJ,McHale N,Levick JR

doi

10.1113/expphysiol.2008.045203

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

350-61

issue

3

eissn

0958-0670

issn

1469-445X

pii

expphysiol.2008.045203

journal_volume

94

pub_type

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