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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

Fluorescence-activated cell sorting (FACS) analysis performed on the MSCs cultured for 10 days. OPN immunostained MSCs were measured by a flow cytometry analysis system (y-axis: the cell number; x-axis: fluorescence intensity). The data shows the synergetic effects of BMP9 and miR-548d-5p on OPN expression of MSCs at day 10 (∗∗P < 0.01 versus control; ##P < 0.01 versus miR-548d-5p; &&P < 0.01 versus BMP9).
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fig4: Fluorescence-activated cell sorting (FACS) analysis performed on the MSCs cultured for 10 days. OPN immunostained MSCs were measured by a flow cytometry analysis system (y-axis: the cell number; x-axis: fluorescence intensity). The data shows the synergetic effects of BMP9 and miR-548d-5p on OPN expression of MSCs at day 10 (∗∗P < 0.01 versus control; ##P < 0.01 versus miR-548d-5p; &&P < 0.01 versus BMP9).

Mentions: The combined impact of BMP9 and miR-548d-5p on protein expression of OPN, the late osteogenic marker, has then been investigated. According to FACS results of Figure 4, the expression of OPN was augmented about 2.5-fold by a separate administration of miR-548d-5p. However, a 9-fold increase of OPN expression was observed, after introduction of BMP9 alone. Moreover, the combination of BMP9 and miR-548d-5p could further enhance the expression of OPN and cause an over 14-fold augmentation of expression. The higher OPN overexpression induced by the combination of BMP9 and miR-548d-5p compared to simple summation of BMP9 and miR-548d-5p similarly suggested potential synergism of BMP9 and PPARγ inhibitor.


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)

Fluorescence-activated cell sorting (FACS) analysis performed on the MSCs cultured for 10 days. OPN immunostained MSCs were measured by a flow cytometry analysis system (y-axis: the cell number; x-axis: fluorescence intensity). The data shows the synergetic effects of BMP9 and miR-548d-5p on OPN expression of MSCs at day 10 (∗∗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

fig4: Fluorescence-activated cell sorting (FACS) analysis performed on the MSCs cultured for 10 days. OPN immunostained MSCs were measured by a flow cytometry analysis system (y-axis: the cell number; x-axis: fluorescence intensity). The data shows the synergetic effects of BMP9 and miR-548d-5p on OPN expression of MSCs at day 10 (∗∗P < 0.01 versus control; ##P < 0.01 versus miR-548d-5p; &&P < 0.01 versus BMP9).
Mentions: The combined impact of BMP9 and miR-548d-5p on protein expression of OPN, the late osteogenic marker, has then been investigated. According to FACS results of Figure 4, the expression of OPN was augmented about 2.5-fold by a separate administration of miR-548d-5p. However, a 9-fold increase of OPN expression was observed, after introduction of BMP9 alone. Moreover, the combination of BMP9 and miR-548d-5p could further enhance the expression of OPN and cause an over 14-fold augmentation of expression. The higher OPN overexpression induced by the combination of BMP9 and miR-548d-5p compared to simple summation of BMP9 and miR-548d-5p similarly suggested potential synergism of BMP9 and PPARγ inhibitor.

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