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

J Gerontol A Biol Sci Med Sci. 2013 Oct;68(10):1170-80. doi: 10.1093/gerona/glt018. Epub 2013 Mar 26.

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.

Keywords: Aging; Bones; Stem cells..

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aging / pathology*
  • Animals
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Calcification, Physiologic / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Female
  • Fibroblast Growth Factor 2 / administration & dosage*
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Middle Aged
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteogenesis / drug effects*
  • Recombinant Proteins / administration & dosage
  • Young Adult

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Recombinant Proteins
  • Fibroblast Growth Factor 2