PDGF-induced proliferation and differentiation of synovial mesenchymal stem cells is mediated by the PI3K-PKB / Akt pathway

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  • Uomizu Mari
    Department of Joint Surgery and Sports Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
  • Muneta Takeshi
    Department of Joint Surgery and Sports Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
  • Ojima Miyoko
    Department of Joint Surgery and Sports Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
  • Sekiya Ichiro
    Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University
  • Koga Hideyuki
    Department of Joint Surgery and Sports Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
  • Tsuji Kunikazu
    Department of Cartilage Regeneration, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University

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Abstract

Background: Platelet-derived growth factors (PDGFs) have been reported to enhance proliferation of synovial mesenchymal stem cells (MSCs) without reducing their multi-lineage differentiation potential in vitro. This study was aimed to elucidate the intracellular molecular pathways activated by PDGFs. Methods: Synovial MSCs were isolated from patients who underwent total knee arthroplasty with institutional approval and patients’ permission. Cell proliferation and differentiation assays were performed in the presence of small inhibitor molecules specific for intracellular kinases. Results: Both PDGF-AA and -BB enhanced cell proliferation in medium containing reduced serum. These effects were significantly reduced by a phosphatidylinositol- 3 kinase (PI3K) inhibitor, LY290042. During chondrogenic spheroid formation in vitro, LY290042 significantly reduced the size of spheroids enhanced by PDGF-AA. LY290042 also significantly inhibited in vitro chondrogenic and osteoblastic differentiation of synovial MSCs. Conclusion: Our data indicated that activation of the PI3K-PKB/ Akt pathway by PDGFs plays an important role in both proliferation and differentiation of synovial MSCs. Hence, these data could be beneficial for optimizing the in vitro culture conditions of synovial MSCs for clinical use.

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