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

Physiology, Basic Medical Sciences, St George's Hospital Medical School, University of London, London SW170RE, UK.
Experimental physiology (Impact Factor: 2.67). 02/2009; 94(3):350-61. DOI: 10.1113/expphysiol.2008.045203
Source: PubMed


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.

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Available from: Karen R Mifsud, Sep 17, 2014
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    • "The concentration of intra-articular HA is greatly reduced in osteo- and rheumatoid arthritis. Studies of HA secretion into rabbit joints in vivo showed that secretion can be stimulated by joint distension, cyclic movement, and protein kinase C activation, as well as by other factors (1, 14, 29, 30, 68). Studies of cultured synoviocytes from the innermost synovial lining (intima) have implicated Ca2+ entry and classic Ca2+-dependent protein kinase C-α (Ca-PKCα) in HA regulation (52, 53), and confirmed that synoviocyte HA secretion is a mechanosensitive process. "
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    Preview · Article · Nov 2010 · AJP Cell Physiology
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    • "We support this contention by demonstrating that inhibiting the translocation of Golgi vesicles, which transport glycosaminoglycans (e.g. hyaluronan22) to the cell surface, inhibited the effect of Ang1 on LP. Brefeldin-A disrupts translocation of cellular material in minutes39 and this is in keeping with our observations of altered LP and glycocalyx depth over this period. "
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