rhBMP2/7 heterodimer: an osteoblastogenesis inducer of not higher potency but lower effective concentration compared with rhBMP2 and rhBMP7 homodimers

Tissue Eng Part A. 2010 Mar;16(3):879-87. doi: 10.1089/ten.TEA.2009.0312.

Abstract

Heterodimeric bone morphogenetic proteins (BMPs) were exhibited to be more potent than and thus potential substitutes for homodimeric BMPs whose clinical application is limited for the drawbacks resulted from their higher effective doses. This study aims to delineate the biofunctional characteristics of recombinant human BMP2/7 (rhBMP2/7) heterodimer in inducing osteoblastogenesis of MC3T3-E1 through in vitro time-course and dose-response studies. rhBMP2/7 heterodimer induced cell migration with a significantly lower optimal concentration and higher peak effect than the respective homodimers. rhBMP2/7 heterodimer induced cell differentiation with significantly lower threshold concentrations but similar maximum effects. On day 28, the area of calcium depositions induced by 50 ng/mL rhBMP2/7 was 12- or 38-fold more than that of 50 ng/mL rhBMP2 or 50 ng/mL rhBMP7, respectively. The results indicated that rhBMP2/7 heterodimer was an osteoblastogenesis inducer of not higher potency but lower effective concentration compared with rhBMP2 and rhBMP7 homodimers.

Publication types

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

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 7 / pharmacology*
  • Bone Morphogenetic Proteins / pharmacology*
  • Calcification, Physiologic / drug effects
  • Calcium / metabolism
  • Cell Line
  • Cell Proliferation / drug effects
  • Chemotaxis / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Humans
  • Mice
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects*
  • Osteoblasts / enzymology
  • Osteocalcin / metabolism
  • Osteogenesis / drug effects*
  • Protein Multimerization / drug effects*
  • Recombinant Proteins / pharmacology*
  • Transforming Growth Factor beta / pharmacology*

Substances

  • BMP7 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Osteocalcin
  • Alkaline Phosphatase
  • Calcium