Representative immunohistochemical sections of hypoxia-inducible factor-1-alpha (HIF-1α) immunoreactivity. Sections obtained from the arthritic synovium treated with intra-articular injections of 'no treatment' (No-tr) (A), saline (SA) (B), and hyaluronan (HA) (C). At higher-power magnification, it is evident that these positive (brown staining) immunoreactivities were clearly localized in both the nucleus and cytoplasm of arthritic synovium in the sections from No-tr (a) and SA (b) animals. Administration of HA (c) to adjuvant-induced rat produced a marked reduction in the immunostaining for HIF-1α. Quantitative analysis (D) of positive-labeled cells in synovium for HIF-1α immunohistochemistry at the early phase of inflammation of each group was presented in the average proportion of labeled neurons (mean ± standard error of the mean). *P <0.05, showed significant differences between groups when either SA or No-tr is compared with HA group using Bonferroni post hoc test. Significant differences were found between HA versus SA groups and HA versus No-tr groups. #P <0.05, showed significant differences between dosages tested by Bonferroni post hoc test. 1D, one dose; 3D, three doses; 3D6d, follow-up at the 6th day after three doses; cart, cartilage; syn, synovial tissue.