Complementary roles of HMGB1 and PRDX4 in the pathophysiology of steroid-associated osteonecrosis of the femoral head: a histopathological and immunohistochemistry study.

Steroid-associated osteonecrosis of the femoral head (SONFH) is closely related to ischemia after corticosteroid treatment as well as the subsequent inflammatory response and oxidative stress. This study examined the temporal and spatial expression of high mobility group box 1 (HMGB1) and peroxiredoxin 4 (PRDX4) in SONFH lesions using immunohistochemistry. Tissue samples from SONFH patients undergoing total hip arthroplasty were compared with those from osteoarthritis (OA) controls. The expression of PRDX4 was significantly reduced in SONFH and was inversely correlated with the oxidative DNA damage marker 8-Hydroxy-2'-deoxyguanosine (8-OHdG). Notably, PRDX4 is strongly expressed in osteoblasts and chondrocytes within callus tissue at the necrotic-viable bone interface, implicating its role in promoting repair through the suppression of oxidative stress. In contrast, most SONFH cases exhibit nuclear-to-cytoplasmic translocation of HMGB1, consistent with its function as a damage-associated molecular pattern (DAMP) that drives inflammatory responses. These findings indicate that HMGB1 acts as an inflammatory mediator during the early phase of SONFH, whereas PRDX4 functions as an oxidative stress regulator during the repair process. Together, these molecules appear to act in a complementary manner to orchestrate the transition from inflammation to tissue regeneration. Their expression dynamics may serve as potential factors for disease progression and reparative activity, while therapeutic strategies targeting HMGB1 signaling or augmenting the expression of PRDX4 may represent promising avenues for intervention.