title: The effect of Platelet Lysate on osteoblast proliferation associated with a transient increase of the inflammatory response in bone regeneration.
abstract: Platelet Lysate (PL) contains a cocktail of growth factors and cytokines, which actively participates in tissue repair and its clinical application has been broadly described. The aim of this study was to assess the regenerative potential of PL for bone repair. We demonstrated that PL stimulation induces a transient increase of the inflammatory response in quiescent human osteoblasts, via NF-kB activation, COX-2 induction, PGE2 production and secretion of pro-inflammatory cytokines. Furthermore, we showed that long-term PL stimulation enhances proliferation of actively replicating osteoblasts, without affecting their differentiation potential, along with changes of cell morphology, resulting in increased cell density at confluence. In confluent resting osteoblasts, PL treatment induced resumption of proliferation, change in cell morphology and increase of cell density at confluence. A burst of PL treatment (24-h) was sufficient to trigger such processes in both conditions. These results correlated with up-regulation of the proliferative and survival pathways ERKs and Akt and with cell cycle re-activation via induction of CyclinD1 and phosphorylation of Rb, following PL stimulation. Our findings demonstrate that PL treatment results in activation and expansion of resting osteoblasts, without affecting their differentiation potential. Therefore PL represents a good therapeutic candidate in regenerative medicine for bone repair.
authors.affiliation: Dept. of Experimental Medicine (DIMES), University of Genoa, L.go R. Benzi 10, Genoa 16132, Italy; AOU San Martino-IST National Cancer Research Institute, L.go R. Benzi 10, Genoa 16132, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ruggiu
authors.forename: Valentina
authors.initials: V
authors.lastname: Ulivi
authors.forename: Francesca
authors.initials: F
authors.lastname: Sanguineti
authors.forename: Ranieri
authors.initials: R
authors.lastname: Cancedda
authors.forename: Fiorella
authors.initials: F
authors.lastname: Descalzi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000276:immunology*; D001861:Bone Regeneration; D002454:Cell Differentiation; D002457:Cell Extracts / Q000276:immunology / Q000494:pharmacology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008875:Middle Aged; D016328:NF-kappa B / Q000276:immunology; D010006:Osteoblasts / Q000166:cytology* / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D002457:Cell Extracts; D016207:Cytokines; D016328:NF-kappa B; D051546:Cyclooxygenase 2
keywords: Fracture repair; Inflammation; Osteoblasts; Platelet Lysate; Proliferation