Teriparatide promotes healing of critical size femur defect through accelerating angiogenesis and degradation of β-TCP in OVX osteoporotic rat model

Biomed Pharmacother. 2017 Dec:96:960-967. doi: 10.1016/j.biopha.2017.11.141. Epub 2017 Dec 6.

Abstract

Accumulating evidence suggests that early angiogenesis has an important effect on the healing of injury. Teriparatide (PTH) is extensively applied for its potent anabolic activity on bone, while little is known about its angiogenic ability which may facilitate new bone formation. In this study, we tested the angiogenic ability of PTH and its effect on degradation of β-tricalcium phosphate (β-TCP) in an ovariectomized (OVX) rat distal femoral metaphysis model. After successful establishment of the OVX model was confirmed, a critical size defect was drilled into each distal femur of the OVX rats. Afterwards all animals were randomly divided into three groups: control group, group β-TCP and group β-TCP+PTH, then rats of group β-TCP+PTH were injected Teriparatide (30 μg/kg) subcutaneous every other day. Four weeks after femur surgery, five specimens from each group were used for Microfil perfusion to reveal blood vessels in the bone defect. The residual rats were harvested for micro-computed tomography, histological analysis and immunochemistry. The results showed Teriparatide facilitated neovascularization, degradation of β-TCP and new bone formation in combination with β-TCP, which may be relevant to neovascularization in an early phase.

Keywords: Angiogenesis; Microfil perfusion; Osteogenesis; Osteoporosis; Teriparatide.

MeSH terms

  • Animals
  • Bone Density Conservation Agents / pharmacology
  • Bone Regeneration / drug effects
  • Calcium Phosphates / metabolism*
  • Female
  • Femur / drug effects*
  • Femur / metabolism
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Osteogenesis / drug effects
  • Osteoporosis / drug therapy*
  • Osteoporosis / metabolism
  • Ovariectomy / methods
  • Rats
  • Rats, Sprague-Dawley
  • Teriparatide / pharmacology*
  • Wound Healing / drug effects*
  • X-Ray Microtomography / methods

Substances

  • Bone Density Conservation Agents
  • Calcium Phosphates
  • beta-tricalcium phosphate
  • Teriparatide