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

Zhang W, Zhang L, Zhou Y, Ji X, Liu J, Liu D, Yin P, Peng Y, Hao M, Zhang L, Tang P - Biomed Res Int (2015)

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

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Combination of BMP9 and miR-548d-5p enhances matrix mineralization and calcium deposition in MSCs. (a) Alizarin red S staining at 2 and 3 w shows the synergetic effects of BMP9 and miR-548d-5p on matrix mineralization; (b) the synergetic effects of BMP9 and miR-548d-5p on calcium deposition in MSCs cultured for 14 days (∗∗P < 0.01 versus control; ##P < 0.01 versus miR-548d-5p; &&P < 0.01 versus BMP9).
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fig5: Combination of BMP9 and miR-548d-5p enhances matrix mineralization and calcium deposition in MSCs. (a) Alizarin red S staining at 2 and 3 w shows the synergetic effects of BMP9 and miR-548d-5p on matrix mineralization; (b) the synergetic effects of BMP9 and miR-548d-5p on calcium deposition in MSCs cultured for 14 days (∗∗P < 0.01 versus control; ##P < 0.01 versus miR-548d-5p; &&P < 0.01 versus BMP9).

Mentions: Finally, we determined the synergistic effects of BMP9 and miR-548d-5p on matrix mineralization and calcium deposition. We found that matrix mineralization assessed by alizarin red staining was remarkably promoted by the combination of BMP and miR-548d-5p, compared with their separate treatment (Figure 5(a)). Additionally, quantitative analysis of calcium deposition similarly showed that BMP9 induced apparently osteogenic calcium secretion compared with treatment by PPARγ inhibiting, and a more enhancement of calcium secretion was achieved when BMP9 accompanied with PPARγ inhibitor was introduced (Figure 5(b)). Taken together, the results of late stage in MSCs further suggested that inhibiting PPARγ could enforce BMP9 induced osteogenic differentiation.


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

Zhang W, Zhang L, Zhou Y, Ji X, Liu J, Liu D, Yin P, Peng Y, Hao M, Zhang L, Tang P - Biomed Res Int (2015)

Combination of BMP9 and miR-548d-5p enhances matrix mineralization and calcium deposition in MSCs. (a) Alizarin red S staining at 2 and 3 w shows the synergetic effects of BMP9 and miR-548d-5p on matrix mineralization; (b) the synergetic effects of BMP9 and miR-548d-5p on calcium deposition in MSCs cultured for 14 days (∗∗P < 0.01 versus control; ##P < 0.01 versus miR-548d-5p; &&P < 0.01 versus BMP9).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644537&req=5

fig5: Combination of BMP9 and miR-548d-5p enhances matrix mineralization and calcium deposition in MSCs. (a) Alizarin red S staining at 2 and 3 w shows the synergetic effects of BMP9 and miR-548d-5p on matrix mineralization; (b) the synergetic effects of BMP9 and miR-548d-5p on calcium deposition in MSCs cultured for 14 days (∗∗P < 0.01 versus control; ##P < 0.01 versus miR-548d-5p; &&P < 0.01 versus BMP9).
Mentions: Finally, we determined the synergistic effects of BMP9 and miR-548d-5p on matrix mineralization and calcium deposition. We found that matrix mineralization assessed by alizarin red staining was remarkably promoted by the combination of BMP and miR-548d-5p, compared with their separate treatment (Figure 5(a)). Additionally, quantitative analysis of calcium deposition similarly showed that BMP9 induced apparently osteogenic calcium secretion compared with treatment by PPARγ inhibiting, and a more enhancement of calcium secretion was achieved when BMP9 accompanied with PPARγ inhibitor was introduced (Figure 5(b)). Taken together, the results of late stage in MSCs further suggested that inhibiting PPARγ could enforce BMP9 induced osteogenic differentiation.

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

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus