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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.

Original publication

DOI

10.1113/expphysiol.2008.045203

Type

Journal article

Journal

Experimental physiology

Publication Date

03/2009

Volume

94

Pages

350 - 361

Addresses

Physiology, Basic Medical Sciences, St George's Hospital Medical School, University of London, London SW170RE, UK.

Keywords

Joints, Animals, Rabbits, Translocation, Genetic, Puromycin, Tetradecanoylphorbol Acetate, Brefeldin A, Cycloheximide, Dactinomycin, Protein Kinase C, Hyaluronic Acid, Protein Synthesis Inhibitors, Injections, Intra-Articular, Protein Biosynthesis, Transcription, Genetic, Biomechanical Phenomena