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

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Glucocorticoid (GC)-induced osteoblast (OB) apoptosis is a key factor in steroid-induced osteonecrosis of the femoral head (SONFH) and osteoporosis.
• Understanding the regulatory mechanisms of GC-induced OB apoptosis is crucial for developing therapeutic strategies.
• Splicing factors play a role in cellular processes, but their involvement in GC-induced OB apoptosis requires elucidation.

Purpose of the Study:

• To investigate the role and mechanism of splicing factors SRSF1 and SRSF2 in glucocorticoid-induced osteoblast apoptosis.
• To explore the potential of SRSF1 and SRSF2 as therapeutic targets for steroid-induced bone diseases.

Main Methods:

• Transcriptome sequencing and bioinformatics analysis to identify differentially expressed genes in GC-treated OB.
• RNA immunoprecipitation and RNA-pull down assays to confirm interactions between SRSF1 and SRSF2.
• Overexpression and knockdown experiments to assess the functional impact of SRSF1 and SRSF2 on GC-induced OB apoptosis.

Main Results:

• SRSF1 and SRSF2 expression were significantly downregulated in GC-treated OB and correlated with apoptosis.
• SRSF1 and SRSF2 directly interact with each other.
• Overexpression of SRSF1 or SRSF2 inhibited GC-induced OB apoptosis, while their knockdown exacerbated it.
• GC treatment inhibited SRSF1/SRSF2 expression, leading to synergistic upregulation of Bim, activation of caspase-9/caspase-3, and ultimately OB apoptosis.

Conclusions:

• SRSF1 and SRSF2 play a protective role against GC-induced OB apoptosis.
• The mechanism involves the synergistic regulation of Bim expression and caspase activation.
• SRSF1 and SRSF2 represent potential therapeutic targets for preventing and treating SONFH and steroid-induced osteoporosis.