Upregulation of microRNA-576-5p protects from steroid-induced avascular necrosis of the femoral head by suppressing ANXA2

Steroid-induced avascular necrosis of the femoral head (SANFH) is a common orthopedic disease. Evidence has shown that microRNAs (miRNAs) played essential roles in the development of SANFH. Nevertheless, the role of miR-576-5p in SANFH remains unknown. The rabbit SANFH models were constructed by injection of horse serum and methylprednisolone. Bone mineral density (BMD) of the proximal femur (including the femoral head), pathological changes, bone cell apoptosis and expressions of OPG/RANK in femoral head bone tissue were assessed upon treatment of up-regulation of miR-576-5p or knockdown of ANXA2. Osteoblasts were extracted from SANFH rabbit femoral head and cultured. Proliferation, apoptosis and mineralization were tested upon treatment of up-regulation of miR-576-5p or knockdown of ANXA2. The targeting relationship between miR-576-5p and ANXA2 was verified. Up-regulated miR-576-5p or down-regulated ANXA2 inhibited the decrease of BMD, improved pathological changes, limited cell apoptosis and increased OPG/RANKL ratio in bone tissues of SANFH rabbits. Up-regulating miR-576-5p or down-regulating ANXA2 promoted proliferation and mineralization and inhibited apoptosis of osteoblasts from SANFH rabbits. In addition, ANXA2 was found to be a target gene of miR-576-5p. Furthermore, overexpression of ANXA2 abolished the protective role of elevated miR-576-5p against femoral head necrosis. Elevated miR-576-5p or reduced ANXA2 repressed the progression of SANFH. This study may provide novel biomarkers for SANFH diagnosis and treatment.