Dose- and time-dependent effects of recombinant human bone morphogenetic protein-2 on the osteogenic and adipogenic potentials of alveolar bone-derived stromal cells

J Periodontal Res. 2012 Oct;47(5):645-54. doi: 10.1111/j.1600-0765.2012.01477.x. Epub 2012 Apr 4.

Abstract

Background and objective: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a well-known growth factor that can induce robust bone formation, and recent studies have shown that rhBMP-2-induced osteogenesis is closely related to adipogenesis. The aim of the present study was to determine the dose- and time-dependent effects of rhBMP-2 on the osteogenic and adipogenic differentiation of human alveolar bone-derived stromal cells (hABCs) in vivo and in vitro.

Material and methods: hABCs were isolated and cultured, and then transplanted using a carrier treated either with or without rhBMP-2 (100 μg/mL) into an ectopic subcutaneous mouse model. Comprehensive histologic and histometric analyses were performed after an 8-wk healing period. To further understand the dose-dependent (0, 10, 50, 200, 500 and 1000 ng/mL) and time-dependent (0, 3, 5, 7 and 14 d) effects of rhBMP-2 on osteogenic and adipogenic differentiation, in vitro osteogenic and adipogenic differentiation of hABCs were evaluated, and the expression of related mRNAs, including those for alkaline phosphatase, osteocalcin, bone sialoprotein, peroxisome-proliferator-activated receptor gamma-2 and lipoprotein lipase, were assessed using quantitative RT-PCR.

Results: rhBMP-2 significantly promoted the osteogenic and adipogenic differentiation of hABCs in vivo, and gradually increased both the osteogenic and adipogenic potential in a dose- and time-dependent manner with minimal deviation in vitro. The expression of osteogenesis- and adipogenesis-associated mRNAs were concomitantly up-regulated by rhBMP-2.

Conclusion: The findings of the present study showed that rhBMP-2 significantly enhanced the adipogenic as well as the osteogenic potential of hABCs in dose- and time-dependent manner. The control of adipogenic differentiation of hABCs should be considered when regenerating the alveolar bone using rhBMP-2.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects*
  • Adult
  • Alkaline Phosphatase / analysis
  • Alveolar Process / cytology
  • Alveolar Process / drug effects*
  • Animals
  • Bone Morphogenetic Protein 2 / administration & dosage
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Bone Regeneration / physiology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Humans
  • Hydroxyapatites / chemistry
  • Integrin-Binding Sialoprotein / analysis
  • Lipoprotein Lipase / analysis
  • Mice
  • Mice, Inbred Strains
  • Middle Aged
  • Osteocalcin / analysis
  • Osteogenesis / drug effects*
  • PPAR gamma / analysis
  • RNA, Messenger / analysis
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Stromal Cells / drug effects*
  • Stromal Cells / transplantation
  • Subcutaneous Tissue / surgery
  • Time Factors
  • Tissue Scaffolds / chemistry
  • Transforming Growth Factor beta / administration & dosage
  • Transforming Growth Factor beta / pharmacology*
  • Up-Regulation

Substances

  • Bone Morphogenetic Protein 2
  • Hydroxyapatites
  • Integrin-Binding Sialoprotein
  • PPAR gamma
  • RNA, Messenger
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Osteocalcin
  • hydroxyapatite-tricalciumphosphate composite
  • Lipoprotein Lipase
  • Alkaline Phosphatase