Objective. To determine the relationship between hypoxia and the expression of Ets-1 and hypoxiainducible factor 1␣ (HIF-1␣) in both normal and inflamed joints. Adjuvant-induced arthritis (AIA) was used as the model system, since it mirrors many aspects of the pathology of rheumatoid arthritis.Methods. Adjuvant arthritis was induced in a group of 10 female Lewis rats. A second group of 10 uninjected female Lewis rats served as naive controls. When a maximum clinical joint score was achieved in the AIA group, all 20 rats were injected with the specific hypoxic cell marker Hypoxyprobe-1 and subsequently killed. Hypoxyprobe-1 adducts, Ets-1, and HIF-1␣ were localized in the joints of the hind feet from these groups using immunohistochemistry.Results. Compared with the joints from control rats, inflamed joints contained markedly more cells with Hypoxyprobe-1 adduct immunoreactivity, Ets-1-immunoreactive nuclei, and nuclear immunoreactivity for both Ets-1 and HIF-1␣.Conclusion. Our results demonstrate the presence of hypoxia in inflamed joints in this experimental model of arthritis. The colocalization of Ets-1 and HIF-1␣ in these hypoxic areas suggests that hypoxia may induce Ets-1 and HIF-1␣ expression during joint inflammation.
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