SRSF1 and SRSF2 synergistically regulate Bim expression to mediate glucocorticoid-induced apoptosis in osteoblasts.

Further study of glucocorticoid (GC) -induced osteoblast (OB) apoptosis and its regulatory mechanism is an important direction to explore the therapeutic strategy of steroid-induced osteonecrosis of the femoral head (SONFH) and steroid-induced osteoporosis. The aim of this study is to elucidate the role and mechanism of splicing factors serine/arginine-rich splicing factor 1 (SRSF1) and SRSF2 in GC-induced OB apoptosis. Transcriptome sequencing and bioinformatics prediction showed that the expression of SRSF1 and SRSF2 was significantly down-regulated in GC-treated OB and was related to GC-induced OB apoptosis. RNA immunoprecipitation and RNA-pull down assay further confirmed the interaction between SRSF1 and SRSF2. Moreover, overexpression of SRSF1 or SRSF2 inhibited GC-induced OB apoptosis, on the contrary, knockdown of SRSF1 or SRSF2 increased the rate of GC-induced OB apoptosis. Mechanistically, GC inhibits the expression of SRSF1 and SRSF2 at the same time, and then synergistically up-regulates the expression of pro-apoptotic molecule Bim, activates caspase-9/caspase-3 cascade, and finally leads to OB apoptosis. The aim of this study is to further investigate the GC-induced OB apoptosis and its regulatory mechanism from the direction of splicing factors, and to provide theoretical guidance and experimental basis for the prevention and treatment of SONFH and steroid-induced osteoporosis.