Aspirin modified strontium-doped β-tricalcium phosphate can accelerate the healing of femoral metaphyseal defects in ovariectomized rats

Biomed Pharmacother. 2020 Dec:132:110911. doi: 10.1016/j.biopha.2020.110911. Epub 2020 Oct 28.

Abstract

The purpose was to observe whether local administration Strontium (Sr) and Aspirin (Asp) can enhance the efficacy of β-Tricalcium phosphate(β-TCP) in the treatment of osteoporotic bone defect. The MC3T3-E1 cells were co-cultured with β-TCP, Sr/β-TCP, Asp-Sr/β-TCP scaffold and induced to osteogenesis, and the cell viability, mineralization ability were observed by MTT, Alizarin Red staining(ARS) and Western blotting(WB). Then this scaffolds were implanted into the femoral epiphysis bone defect model of ovariectomized(OVX) rats for 8 weeks. X-ray, Micro-CT, histology and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and explore the possible mechanism. MTT, ARS results show that the cell mineralization and viability of Asp-Sr/β-TCP group is significantly higher than Control group, β-TCP group and Sr/β-TCP group. Protein expression show that the osteogenic protein expression such as ALP、OP、RUNX-2、OC and COL-1 of Asp-Sr/β-TCP group is significantly higher than Control group, β-TCP group and Sr/β-TCP group. X-ray images, Micro-CT and Histological analysis evaluation show that, group Asp-Sr/β-TCP presented the strongest effect on bone regeneration and bone mineralization, when compared with β-TCP group and Sr/β-TCP group. RT-qPCR analysis show that Asp-Sr/β-TCP, β-TCP group and Sr/β-TCP group showed increased BMP2, Smad1, OPG than the OVX group(p < 0.05), while Asp-Sr/β-TCP exhibited decreased TNF-α、IFN-γ and RANKL than the OVX group(p < 0.05). Our current study demonstrated that Asp-Sr/ β-TCP is a scheme for rapid repair of femoral condylar defects, and these effects may be achieved by inhibiting local inflammation and through BMP-2/Smad1 and OPG/RANKL signaling pathway.

Keywords: Aspirin; Inflammation; Osteoporotic bone defect; Strontium; β-Tricalcium phosphate.

Publication types

  • Comparative Study

MeSH terms

  • 3T3 Cells
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Aspirin / pharmacology*
  • Bone Density / drug effects
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Remodeling / drug effects*
  • Bone Substitutes / pharmacology*
  • Calcium Phosphates / pharmacology*
  • Disease Models, Animal
  • Female
  • Femur / drug effects*
  • Femur / metabolism
  • Femur / pathology
  • Humans
  • Mice
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteogenesis / drug effects*
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / metabolism
  • Osteoporosis, Postmenopausal / pathology
  • Osteoprotegerin / metabolism
  • Ovariectomy
  • RANK Ligand / metabolism
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Smad1 Protein / metabolism
  • Strontium / pharmacology*
  • Wound Healing / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Substitutes
  • Calcium Phosphates
  • Osteoprotegerin
  • RANK Ligand
  • Smad1 Protein
  • Smad1 protein, rat
  • Tnfrsf11b protein, rat
  • beta-tricalcium phosphate
  • Aspirin
  • Strontium