title: Oncostatin M induces leukocyte infiltration and cartilage proteoglycan degradation in vivo in goat joints.
abstract: OBJECTIVE
  To evaluate the effect of intraarticular injections of recombinant human oncostatin M (rHuOSM) in the goat joint.
  
  
  METHODS
  One milliliter of endotoxin-free normal saline (vehicle) containing either 40 ng, 200 ng, or 1,000 ng of rHuOSM was injected into the right radiocarpal joints (RCJs) of 12 male angora goats, while the left RCJs were injected with an equivalent volume of vehicle alone. In subsequent studies, the right and left RCJs of 8 male angora goats were injected with 200 ng of rHuOSM, and 1 hour later, the right RCJs were injected with either 5 microg of recombinant murine leukemia inhibitory factor binding protein (rMuLBP) or 1 mg of recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) in 1 ml of vehicle, while the left RCJs received 1 ml of vehicle alone. Goat joints were examined for clinical features of inflammation, and synovial fluid (SF) was aspirated on day 0 (before injection) and at days 2 and 6 postinjection.
  
  
  RESULTS
  Injections of rHuOSM stimulated dose-dependent increases in the carpal:metacarpal ratio, SF volume, and SF leukocyte numbers, and stimulated dose-dependent decreases in the cartilage proteoglycan (PG) content ex vivo and PG synthesis. No significant changes were observed in the control joints that received saline alone, or between RCJs that were injected with 200 ng rHuOSM followed by 5 microg rMuLBP and RCJs that were injected with 200 ng of rHuOSM alone, except in respect to synovial fluid keratan sulfate concentrations, where a modest statistically significant reduction was observed in the joints injected with the combination of rHuOSM and rMuLPB. In contrast, RCJs injected with 200 ng rHuOSM followed by 1 mg of rHuIL-1Ra had significantly lower SF volumes (P<0.0001) and a significantly higher rate of ex vivo PG synthesis (P<0.0001).
  
  
  CONCLUSIONS
  These results indicate that rHuOSM stimulates inflammation and modulates cartilage PG metabolism in vivo. Some of the effects of rHuOSM in vivo appear to be due, in part, to elaboration of IL-1. Even at very high doses, however, the rHuIL-1Ra did not attenuate OSM-mediated cartilage PG resorption. Thus, OSM has the potential to contribute to synovitis in vivo and can stimulate cartilage PG resorption in vivo, independent of IL-1.
authors.affiliation: University of Western Australia, and Royal Perth Hospital, Perth, Australia.
authors.forename: M C
authors.initials: MC
authors.lastname: Bell
authors.forename: G J
authors.initials: GJ
authors.lastname: Carroll
authors.forename: H M
authors.initials: HM
authors.lastname: Chapman
authors.forename: J N
authors.initials: JN
authors.lastname: Mills
authors.forename: W
authors.initials: W
authors.lastname: Hui
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D006041:Goats / Q000378:metabolism*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007632:Keratan Sulfate / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D011509:Proteoglycans / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013582:Synovial Fluid / Q000166:cytology*
chemical_list: D016207:Cytokines; D006131:Growth Inhibitors; D018836:Inflammation Mediators; C508351:OSM protein, human; D010455:Peptides; D011453:Prostaglandins; D011509:Proteoglycans; D011994:Recombinant Proteins; D053683:Oncostatin M; D007632:Keratan Sulfate