title: Cyclic tensile stress exerts antiinflammatory actions on chondrocytes by inhibiting inducible nitric oxide synthase.
abstract: Continuous passive motion manifests therapeutic effects on inflamed articular joints by an as-yet-unknown mechanism. Here, we show that application of cyclic tensile stress (CTS) in vitro abrogates the catabolic effects of IL-1beta on chondrocytes. The effects of CTS are mediated by down-regulation of IL-1beta-dependent inducible NO production, and are directly attributed to the inhibition of inducible NO synthase (iNOS) mRNA expression and protein synthesis. The inhibition of iNOS induction by CTS is paralleled by abrogation of IL-1beta-induced down-regulation of proteoglycan synthesis. Furthermore, CTS inhibits iNOS expression and up-regulates proteoglycan synthesis at concentrations of IL-1beta frequently observed in inflamed arthritic joints, suggesting that the actions of CTS may be clinically relevant in suppressing the sustained effects of pathological levels of IL-1beta in vivo. These results are the first to demonstrate that mechanisms of the intracellular actions of CTS in IL-1beta-activated chondrocytes are mediated through inhibition of a key molecule in the signal transduction pathway that leads to iNOS expression.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Innsbruck Medical Center, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Gassner
authors.forename: M J
authors.initials: MJ
authors.lastname: Buckley
authors.forename: H
authors.initials: H
authors.lastname: Georgescu
authors.forename: R
authors.initials: R
authors.lastname: Studer
authors.forename: M
authors.initials: M
authors.lastname: Stefanovich-Racic
authors.forename: N P
authors.initials: NP
authors.lastname: Piesco
authors.forename: C H
authors.initials: CH
authors.lastname: Evans
authors.forename: S
authors.initials: S
authors.lastname: Agarwal
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology; D008954:Models, Biological; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013718:Tensile Strength / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D011509:Proteoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II