title: Fibroblast growth factor-2 and bone morphogenetic protein-2 have a synergistic stimulatory effect on bone formation in cell cultures from elderly mouse and human bone.
abstract: Combined regimens of fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2) were investigated to stimulate osteogenic differentiation. In young mouse calvaria-derived cells, FGF-2 (0.16ng/mL) in combination with BMP-2 (50ng/mL) did not enhance mineralization, but in old mouse cells it resulted in more mineralization than BMP-2 alone. In young long bone mouse cultures, FGF-2 enhanced mineralization relative to BMP-2 alone, but in old cultures, lower dose of FGF-2 (0.016ng/mL) was necessary. In neonatal mouse calvarial cells, sequential delivery of low-dose FGF-2 and low-dose BMP-2 (5ng/mL) was more stimulatory than co-delivery. In young human cultures, 0.016ng/mL of FGF-2 did not enhance mineralization, in combination with 5ng/mL of BMP-2, but in older cultures, codelivery of FGF-2 and BMP-2 was superior to BMP-2 alone. In conclusion, BMP-2 treatment alone was sufficient for maximal mineralization in young osteoblast cultures. However, coadministration of FGF-2 and BMP-2 increases mineralization more than BMP-2 alone in cultures from old and young mouse long bones and old humans but not in young mouse calvarial cultures.
authors.affiliation: Department of Surgery MC-3105, University of Connecticut Health Center, Farmington, CT 06030-3105. gronowicz@nso1.uchc.edu.
authors.forename: Liisa T
authors.initials: LT
authors.lastname: Kuhn
authors.forename: Guomin
authors.initials: G
authors.lastname: Ou
authors.forename: Lyndon
authors.initials: L
authors.lastname: Charles
authors.forename: Marja M
authors.initials: MM
authors.lastname: Hurley
authors.forename: Craig M
authors.initials: CM
authors.lastname: Rodner
authors.forename: Gloria
authors.initials: G
authors.lastname: Gronowicz
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D002113:Calcification, Physiologic / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage; D055815:Young Adult
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2
keywords: Aging; Bones; Stem cells.