Downregulating STAT1/caspase-3 signaling with fludarabine to alleviate progression in a rat model of steroid-induced avascular necrosis of the femoral head.

Steroid-induced avascular necrosis of the femoral head (SANFH) is mainly induced by glucocorticoids. Fludarabine (Flu) is a specific signal transducer and activator of transcription 1 (STAT1) inhibitor. In this study, we investigated the effect of Flu on SANFH and the role played by the STAT1/caspase-3 signaling pathway. Sprague-Dawley rats were divided into control, SANFH, and Flu-treated SANFH groups. Femoral head tissues were collected for hematoxylin-eosin (H&E) staining and Western blot analysis. The latter was used to measure the levels of stat1, phospho-stat1, caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, Bax, cytochrome C, Bak, B-cell lymphoma-extra large, and B-cell lymphoma-2 protein expression. The results showed that Flu regulates protein expression in dexamethasone (Dex)-induced SANFH. H&E staining showed a decrease in the ratio of empty lacunae induced by Dex. Taken together, our study demonstrated the involvement of the STAT1/caspase-3 signaling pathway in SANFH and the potential of Flu as a therapeutic agent for patients with SANFH.