IGF2BP3 facilitates the osteogenic differentiation of bone marrow mesenchyml stem cells via upregulating KLK4.

BACKGROUND

Osteoporosis (OP) is a chronic metabolic bone disease marked by imbalance in osteoblast and osteoclast activity. This study was aimed to explore the molecular mechanism underlying osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) to discover the novel target for OP.

METHODS

RT-qPCR was used for mRNA expression detection of Kallikrein 4 (KLK4) and Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). Protein detection was conducted by western blot. The osteogenic differentiation of BMSCs was evaluated through alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS). Interaction between IGF2BP3 and KLK4 was analyzed using RNA immunoprecipitation (RIP) assay and actinomycin D assay.

RESULTS

KLK4 was downregulated in OP patients, and upregulated in osteogenically differentiated BMSCs. KLK4 overexpression promoted the osteogenic differentiation of BMSCs. IGF2BP3 enhanced the expression of KLK4. KLK4 upregulation restored the effect of IGF2BP3 knockdown on the osteogenic differentiation of BMSCs. Moreover, IGF2BP3 overexpression enhanced the osteogenic differentiation of BMSCs by promoting KLK4.

CONCLUSION

These evidences suggested that IGF2BP3 contributed to the osteogenic differentiation of BMSCs via mediating KLK4, providing a potential target for treatment of OP.