IGF2BP2, an RNA‐binding protein regulates cell proliferation and osteogenic differentiation by stabilizing SRF mRNA

Osteoblast proliferation and osteogenic differentiation (OGD) are regulated by complex mechanisms. The roles in cell proliferation and OGD of RNA‐binding proteins in the insulin‐like growth factor 2 mRNA‐binding protein (IGF2BP) family remain unclear. To elucidate this, we examined the differential expression of IGF2BP2 in OGD and osteoporosis, and the expression profile of IGF2BP2‐binding RNA in vitro. We screened the GEO database for differential expression of IGF2BP in OGD and osteoporosis, and verified the RNAs interacting with IGF2BP2 via RNA immunoprecipitation sequencing assays. The proliferation and OGD of IGF2BP2‐ and serum response factor (SRF)‐treated cells, and their regulatory mechanisms, were examined. IGF2BP2 was differentially expressed in OGD and osteoporosis. The RNA immunoprecipitation sequencing assay identified all of the RNAs that bind with IGF2BP2, and revealed SRF as a target of IGF2BP2. IGF2BP2 and SRF inhibition impaired MC3T3‐E1 cell growth but promoted OGD. The mRNA stability analysis revealed that IGF2BP2 enhanced SRF mRNA stability against degradation. In summary, IGF2BP2 is a potential biomarker and therapeutic target for osteoporosis and OGD. Osteoblast proliferation and osteogenic differentiation (OGD) are regulated by multiple molecules and complex mechanisms. N6‐methyladenosine (m6A) plays a critical role in the epigenetic regulation of cell proliferation and OGD. The insulin‐like growth factor 2 mRNA‐binding protein (IGF2BP) family of proteins are m6A regulatory factors involved in numerous cellular functions. However, their potential role in cell proliferation and OGD is unclear. In our study, we showed that IGF2BP2 was identified to promote the proliferation of osteoblasts while suppressing OGD through the enhancement of SRF mRNA stability.