Expression of hypoxia-inducible factor-1α (HIF-1α) in RA synovium and fibroblast-like synoviocytes under normoxic and hypoxic conditions. (a) Under normoxic conditions, HIF-1α expression in fresh synovial explants was patchy and confined to some cells in the lining layer. (b) When fresh RA tissue explants were cultured in hypoxic conditions (1% O2), nuclear staining for HIF-1α was readily detected in the lining cells. (c, d) A similar pattern of expression was seen in fibroblast-like synoviocytes where under normoxic conditions no HIF-1α staining was detected (c), whereas under hypoxic conditions intense nuclear staining was seen maximally at 4–6 hours (d). Reproduced, with permission, from .