title: Acidic preparations of lysed platelets upregulate proliferative pathways in osteoblast-like cells as demonstrated by genome-wide microarray analysis.
abstract: Platelets contain numerous growth factors essential for wound and fracture healing. We investigated the gene expression in human osteoblast-like cells stimulated with lysed platelets prepared in acidic, neutral, or alkaline buffers. Lysed platelets prepared in buffers at pH 5.4, 7.4, and 7.9, were added after neutralization to hFOB 1.19 cells. Genome-wide microarray analysis was performed using the Affymetrix GeneChip 7G Scanner. Biometric, cluster, and pathway analyses were performed with GeneSpring GX. Biometric analyses demonstrated that 53 genes were differentially regulated (p ≤ 0.005, ≥2-fold increase). Pathway analysis revealed 10 significant pathways of which eight are common ones regulating bone formation and cancer growth. Eleven genes were selected for quantitative real-time polymerase chain reaction (PCR) based on the microarray analysis of the lysed platelets prepared in the pH 5.4 experiments. In conclusion, acidic preparations of lysed platelet concentrates release factors essential for cell proliferation and particularly cell metabolism under hypoxic conditions. The genetic response from these factors was dominated by genes associated with the same pathways observed in bone formation and cancer growth. Activation of TGF-β in the acidic preparation could be a stimulatory key factor of cell proliferation. These results support the hypothesis that acidification of platelets modifies the stimulatory response of mesenchymal cells in vitro, which is analogous with the observed milieu of a low pH present in wound and fracture sites, as well as in growing tumors.
authors: Division of Orthopaedics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences at Linköping University, Linköping, Sweden.
authors: Ola
authors: O
authors: Wahlström
authors: Cecilia Halling
authors: CH
authors: Linder
authors: Anna
authors: A
authors: Ansell
authors: Anders
authors: A
authors: Kalén
authors: Mats
authors: M
authors: Söderström
authors: Per
authors: P
authors: Magnusson
mesh_terms: D000143:Acids / Q000737:chemistry; D001792:Blood Platelets / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002457:Cell Extracts / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017102:Fracture Healing / Q000502:physiology; D020869:Gene Expression Profiling; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*
chemical_list: D000143:Acids; D002457:Cell Extracts; D016212:Transforming Growth Factor beta