{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T21:58:31Z","timestamp":1759960711149},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,7,1]],"date-time":"2003-07-01T00:00:00Z","timestamp":1057017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2003,7]]},"abstract":"<jats:p>Hyaluronan (HA) is important for joint cavitation, lubrication, volume regulation and synovial fluid drainage but little is known about the regulation of joint HA synthesis\/secretion <jats:italic>in vivo<\/jats:italic>. We investigated whether HA secretion into joints <jats:italic>in vivo<\/jats:italic> can be regulated by protein kinase C (PKC). Secretion into the knee joint cavity of anaesthetised rabbits was measured over 6 h by washout and chromatography. Joints received intra\u2010articular injections of Ringer vehicle (control) or an activator of classical PKC isoforms, phorbol\u201012\u2010myristate\u201013\u2010acetate (PMA), at 20\u20132000 ng ml<jats:sup>\u22121<\/jats:sup>. The effects of PKC inhibition by bisindolylmaleimide (BIM) and protein synthesis inhibition by cycloheximide (CX) on basal and stimulated HA secretion were also studied. The endogenous HA mass, 181 \u00b1 8 \u03bcg (<jats:italic>n<\/jats:italic>= 26, mean \u00b1<jats:sc>s.e.m<\/jats:sc>.), and basal secretion rate, 4.4 \u00b1 0.4 \u03bcg h<jats:sup>\u22121<\/jats:sup>, indicated a turnover time of 41 h. Secretion rate showed a dose\u2010dependent response to PMA (<jats:styled-content><jats:italic>n<\/jats:italic>= 30<\/jats:styled-content>), rising 5\u2010fold to 21.7 \u00b1 5.0 \u03bcg h<jats:sup>\u22121<\/jats:sup> (<jats:styled-content><jats:italic>n<\/jats:italic>= 5<\/jats:styled-content>) at 2000 ng ml<jats:sup>\u22121<\/jats:sup> PMA (<jats:italic>P<\/jats:italic> &lt; 0.0001, one\u2010way ANOVA). PMA\u2010induced stimulation was partially suppressed by CX (HA secretion: 5.8 \u00b1 1.7 \u03bcg h<jats:sup>\u22121<\/jats:sup>, <jats:italic>n<\/jats:italic>= 8, <jats:italic>P<\/jats:italic> &lt; 0.01) and totally blocked by BIM (HA secretion: 3.2 \u00b1 0.6 \u03bcg h<jats:sup>\u22121<\/jats:sup>, <jats:italic>n<\/jats:italic>= 9, <jats:italic>P<\/jats:italic> &lt; 0.001). Basal HA secretion was unaffected by CX over 6 h (4.2 \u00b1 0.7 \u03bcg h<jats:sup>\u22121<\/jats:sup>, <jats:italic>n<\/jats:italic>= 8) but was reduced by 29 % by BIM (3.1 \u00b1 0.6 \u03bcg h<jats:sup>\u22121<\/jats:sup>, <jats:italic>n<\/jats:italic>= 10, <jats:italic>P<\/jats:italic>= 0.03). It is concluded that: (1) PKC can stimulate HA secretion into joints <jats:italic>in vivo<\/jats:italic> through mechanisms involving protein synthesis <jats:italic>de novo<\/jats:italic> as well as phosphorylation; (2) basal HA secretion is only partially PKC dependent; and (3) hyaluronan synthase turnover time is &gt; 6 h <jats:italic>in vivo<\/jats:italic>, which is slower than <jats:italic>in vitro<\/jats:italic> (&lt; 2\u20133 h).<\/jats:p>","DOI":"10.1113\/jphysiol.2003.038943","type":"journal-article","created":{"date-parts":[[2003,5,27]],"date-time":"2003-05-27T00:16:22Z","timestamp":1053994582000},"page":"631-640","source":"Crossref","is-referenced-by-count":17,"title":["Regulation of hyaluronan secretion into rabbit synovial joints <i>in vivo<\/i> by protein kinase C"],"prefix":"10.1113","volume":"550","author":[{"given":"C. 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