In vivo dynamic analysis of BMP-2-induced ectopic bone formation

Sci Rep. 2020 Mar 16;10(1):4751. doi: 10.1038/s41598-020-61825-2.

Abstract

Bone morphogenetic protein (BMP)-2 plays a central role in bone-tissue engineering because of its potent bone-induction ability. However, the process of BMP-induced bone formation in vivo remains poorly elucidated. Here, we aimed to establish a method for intravital imaging of the entire process of BMP-2-induced ectopic bone formation. Using multicolor intravital imaging in transgenic mice, we visualized the spatiotemporal process of bone induction, including appearance and motility of osteoblasts and osteoclasts, angiogenesis, collagen-fiber formation, and bone-mineral deposition. Furthermore, we investigated how PTH1-34 affects BMP-2-induced bone formation, which revealed that PTH1-34 administration accelerated differentiation and increased the motility of osteoblasts, whereas it decreased morphological changes in osteoclasts. This is the first report on visualization of the entire process of BMP-2-induced bone formation using intravital imaging techniques, which, we believe, will contribute to our understanding of ectopic bone formation and provide new parameters for evaluating bone-forming activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / physiology*
  • Bone and Bones / diagnostic imaging*
  • Bone and Bones / metabolism
  • Bone and Bones / physiology*
  • Calcification, Physiologic / drug effects
  • Calcification, Physiologic / genetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Collagen / metabolism
  • Mice, Transgenic
  • Molecular Imaging / methods*
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / genetics
  • Osteoblasts / physiology*
  • Osteoclasts / physiology*
  • Osteogenesis / drug effects
  • Osteogenesis / genetics*
  • Osteogenesis / physiology*
  • Peptide Fragments / pharmacology
  • Teriparatide / analogs & derivatives
  • Teriparatide / pharmacology

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Peptide Fragments
  • Teriparatide
  • Collagen
  • parathyroid hormone (1-34)amide