Oncostatin M induces leukocyte infiltration and cartilage proteoglycan degradation in vivo in goat joints

Objective, To evaluate the effect of intraarticular injections of recombina nt human oncostatin M (rHuOSM) in the goat joint. Methods. One milliliter of endotoxin-free normal saline (vehicle) containin g either 40 ng, 200 ng, or 1,000 ng of rHuOSM was injected into the right r adiocarpal 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 o f rHuOSM, and 1 hour later, the right RCJs were injected with either 5 mu g of recombinant murine leukemia inhibitory factor binding protein (rMuLBP) or 1 mg of recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) in 1 mi of vehicle, while the left RCJs received 1 mi of vehicle alone. Goa t 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 po stinjection, Results, Injections of rHuOSM stimulated dose-dependent increases in the ca rpal:metacarpal ratio, SF volume, and SF leukocyte numbers, and stimulated dose-dependent decreases in the cartilage proteoglycan CPG) content ex vivo and PG synthesis. No significant changes were observed in the control join ts that received saline alone, or between RCJs that were injected with 200 ng rHuOSM followed by 5 mu g rMuLBP and RCJs that were injected with 200 ng of rHuOSM alone, except in respect to synovial fluid keratan sulfate conce ntrations, where a modest statistically significant reduction was observed in the joints injected with the combination of rHuOSM and rMuLPB, In contra st, RCJs injected with 200 ng rHuOSM followed by 1 mg of rHuIL-1Ra had sign ificantly lower SF volumes (P < 0.0001) and a significantly higher rate of ex vivo PG synthesis (P < 0.0001). Conclusion. 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 r esorption. Thus, OSM has the potential to contribute to synovitis in vivo a nd can stimulate cartilage PG resorption in vivo, independent of IL-1.