【Introduction】
Differentiation of mesenchymal stem cells (MSCs) into osteoblasts is an essential process for the acquisition and maintenance of bone mass. However, its regulatory mechanism remains unclear. In this study, we focused on the forkhead transcription factor Foxf2, whose role in bone remodeling is still unknown. Thus, this study aimed to elucidate the regulatory mechanism of MSCs differentiation into osteoblasts by Foxf2.
【Methods】
Foxf2 was overexpressed or knockdown in mouse bone marrow-derived mesenchymal stem cell-like ST2 cells, and the expression levels of osteogenic differentiation markers were measured by quantitative RT-PCR. Then, we generated MSC-specific Foxf2 knockout mice (cKO mice) using Prx1 promoter and analyzed bone volume by μCT. Furthermore, we analyzed the target genes of Foxf2 by RNA-seq, Western blotting, and reporter assay. Finally, the in vivo effect of Foxf2 knockdown was evaluated by μCT in the bone marrow ablation model.
【Results】
Overexpression of Foxf2 in MSCs inhibited their differentiation into osteoblasts, while knockdown of Foxf2 promoted their differentiation into osteoblasts. cKO mice showed no obvious abnormality in bone resorption but enhanced bone formation, resulting in a high bone mass phenotype. Molecular biological analysis revealed that Foxf2 regulates the differentiation of MSCs into osteoblasts by modulating the Wnt pathway. In addition, Foxf2 knockdown promoted bone regeneration in vivo.
【Discussion/Conclusion】
Foxf2 regulates the differentiation of MSCs into osteoblasts via Wnt signaling. From a clinical point of view, the regulation of Foxf2 expression may be useful in promoting osteogenesis.