Platelet-released supernatants increase migration and proliferation, and decrease osteogenic differentiation of bone marrow-derived mesenchymal progenitor cells under in vitro conditions.
Platelet-rich plasma is currently promoted to serve as an adjuvant for bone grafts to enhance quantity and quality of newly forming bone; however, the underlying cellular mechanisms are not fully understood. We show here that supernatants of leukocyte-depleted thrombin-activated platelets increase migration and proliferation, and decrease osteogenic differentiation of bone marrow-derived mesenchymal progenitor cells under in vitro conditions. Using neutralizing antibodies raised against platelet-derived growth factor (PDGF), the observed effects of platelet-released supernatants were diminished. The mitogenic response was also decreased when extracellular signal-regulated protein kinase (ERK) signalling was inhibited by PD98059; however, PD98059 did not reverse the effects of platelet-released supernatants on migration and osteogenic differentiation. Consistent with an ERK-mediated mitogenic activity, incubation of serum-starved mesenchymal cell progenitors with platelet-released supernatants increased phosphorylation of the kinase. Together, these observations indicate that PDGF is a key factor released upon platelet activation that can increase migration and proliferation, and decreases osteogenic differentiation of mesenchymal progenitor cells under in vitro conditions. The results further suggest that ERK signalling is required to mediate the mitogenic response to platelet-released supernatants.
Dental School , Deparment of Oral Surgery, Uibersity of Vienna, Austria. reinhard.gruber@akh-wien.ac.at
Reinhard
R
Gruber
Florian
F
Karreth
Barbara
B
Kandler
Gabor
G
Fuerst
Antal
A
Rot
Michael B
MB
Fischer
Georg
G
Watzek
D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013917:Thrombin / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000906:Antibodies; D017077:Culture Media, Conditioned; D005419:Flavonoids; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; D014157:Transcription Factors; D015675:Osteocalcin; D020928:Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase; D013917:Thrombin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one