title: Synergistic Effects of BMP9 and miR-548d-5p on Promoting Osteogenic Differentiation of Mesenchymal Stem Cells.
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.
authors.affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: LiCheng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Medical Department, Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: XinRan
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: JianHeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: DaoHong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yin
authors.affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Hao
authors.affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: LiHai
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, General Hospital of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: PeiFu
authors.initials: P
authors.lastname: Tang
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D047495:PPAR gamma / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; C561887:MIRN548 microRNA, human; D035683:MicroRNAs; D047495:PPAR gamma; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human