Synergistic Effects of BMP9 and miR-548d-5p on Promoting Osteogenic Differentiation of Mesenchymal Stem Cells

Abstract EN

Various stimulators have been reported to promote MSC osteogenic differentiation via different pathways such as bone morphogenetic protein 9 (BMP9) through influencing COX-2 and miR-548d-5p through targeting peroxisome proliferator-activated receptor-γ (PPARγ).

Whether synergistic effects between BMP9 and miR-548d-5p existed in promoting osteogenesis from MSCs was unclear.

In the study, the potential synergistic effects of BMP9 and miR-548d-5p on human MSC differentiation were investigated.

Osteogenic differentiation of MSCs treated with BMP9 or miR-548d-5p was detected with multimodality of methods.

The results demonstrated that BMP9 and miR-548d-5p significantly influenced COX-2 and PPARγ, respectively.

BMP9 also influenced the expression of PPARγ, but no significant effect of miR-548d-5p on COX-2 was observed.

When BMP9 and miR-548d-5p were combined, more potent effects on both COX-2 and PPARγ were observed than BMP9 or miR-548d-5p alone.

Consistently, osteogenic analysis at different timepoints demonstrated that osteogenic genes, ALP activity, calcium deposition, OPN protein, and matrix mineralization were remarkably upregulated by BMP9/miR-548d-5p compared with BMP9 or miR-548d-5p alone, indicating the synergetic effects of BMP9 and miR-548d-5p on osteogenic differentiation of MSCs.

Our study demonstrated that regulating different osteogenic regulators may be an effective strategy to promote bone tissue regeneration for bone defects.