Open AccessPlatelet‐rich plasma increases proliferation of tendon cells by modulating Stat3 and p27 to up‐regulate expression of cyclins and cyclin‐dependent kinases
Author(s) -
Yu T.Y.,
Pang J.H. S.,
Wu K. P.H.,
Lin L.P.,
Tseng W.C.,
Tsai W.C.
Publication year - 2015
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12189
Subject(s) - cyclin dependent kinase , cell cycle , cyclin , cell growth , microbiology and biotechnology , biology , kinase , cyclin d , chemistry , cell , biochemistry
Objectives To investigate effects of platelet‐rich plasma on tendon cell proliferation and the underlying molecular mechanisms. Materials and methods Platelet‐rich plasma was prepared manually by two‐step centrifugation. Proliferation was evaluated in cultured rat tendon cells by the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide assay. Cell cycle progression was assessed by flow cytometry. Messenger RNA expression of proliferating cell nuclear antigen ( PCNA ), cyclin E1, A2 and B1, and cyclin‐dependent kinases (Cdks) 1 and 2 was assessed by real‐time polymerase chain reaction. Protein expression of the above cyclins and Cdks and of signal transducer and activator of transcription (Stat) 3 and p27 was evaluated by western blotting. Results Platelet‐rich plasma used in the present study had concentrations of platelets, TGF ‐β1 and PDGF over 3‐fold higher than normal whole blood. Platelet‐rich plasma enhanced tendon cell proliferation ( P = 0.008) by promoting G 1 /S phase transition in the cell cycle, and increased expression of PCNA , cyclin E1, A2 and B1, Cdks1 and 2, and phosphorylated Stat3, while inhibiting p27 expression. Conclusions Platelet‐rich plasma contains high concentrations of TGF ‐β1 and PDGF that increase tendon cell proliferation by modulating Stat3/p27 Kip1 , which enhances expression of cyclin–Cdk complexes that promote cell cycle progression. These results provide molecular evidence for positive effects of platelet‐rich plasma on tendon cell proliferation, which can be useful in clinical applications of tendon injury.