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Activated platelets increase fibrinolysis of mesenchymal progenitor cells
Author(s) -
Agis Hermann,
Kandler Barbara,
Fischer Michael B.,
Watzek Georg,
Gruber Reinhard
Publication year - 2009
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.20819
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , chemistry , progenitor cell , pi3k/akt/mtor pathway , platelet , plasminogen activator , signal transduction , immunology , biology , stem cell , endocrinology
Bone regeneration is initiated by the formation of a blood clot. Activated platelets within this fibrin‐rich matrix release signaling molecules that can attract mesenchymal progenitor cells. To gain insight into the cellular mechanism by which activated platelets can support the immigration of mesenchymal progenitors, we have tested the hypothesis that platelet‐released signaling molecules increase the capacity of bone marrow stromal cells (BMSC) to activate plasminogen. We report herein that platelet‐released supernatants (PRS) elevate total urokinase‐type plasminogen activator (uPA) and total plasminogen activator inhibitor‐1 (PAI‐1) levels in BMSC, as assessed by immunoassay. Quantitative polymerase chain reaction showed an upregulation of uPA, uPA receptor, and PAI‐1. Zymography and kinetic analysis based on casein hydrolysis revealed enhanced activity of cell‐associated uPA upon exposure of BMSC to PRS. Inhibiting c‐Jun N‐terminal kinase (JNK) and phosphatidylinositol 3‐kinase (PI3K) signaling reduced uPA production and decreased plasminogen activation. Corresponding Western blot analysis showed increased phosphorylation of JNK and AKT in BMSC treated with PRS. These results suggest that activated platelets can enhance the plasminogen activation capacity of mesenchymal progenitors through the stimulation of uPA production, requiring JNK and PI3K/AKT signaling. By this mechanism platelets may contribute to the organization of the blood clot during bone regeneration. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 972–980, 2009