Enhanced proliferation and differentiation effects of a CGRP- and Sr-enriched calcium phosphate cement on bone mesenchymal stem cells

J Appl Biomater Funct Mater. 2016 Nov 2;14(4):e431-e440. doi: 10.5301/jabfm.5000295.

Abstract

Introduction: Because of its good osteoconductivity, strontium (Sr) ranelate has been extensively used as a bone substitute for the treatment of bone disorders. To facilitate treatment, Sr is also incorporated into calcium phosphate cement (Sr-CPC); however, the Sr from Sr-CPC is not sufficient to induce a significant increase of bone mass in an ovariectomized rat model. To improve the efficiency of Sr-CPC, we developed a calcitonin gene-related peptide (CGRP)- and Sr-enriched CPC (CGRP-Sr-CPC).

Methods: We used X-ray diffraction and Fourier transform infrared spectroscopy to measure properties of CGRP-Sr-CPC. We also employed a cell proliferation assay, alkaline phosphatase (ALP) assay and real-time PCR to assess the effects of CPC implants on proliferation and differentiation of bone mesenchymal stem cells (BMSCs) from an ovariectomized rat model.

Results: CGRP did not change the composition, pore sizes and compressive strength of the cement body as compared with Sr-CPC. Meanwhile, CGRP-Sr-CPC did not show cell cytotoxicity to BMSCs. Further, CGRP and Sr released from CGRP-Sr-CPC significantly enhanced the cell proliferation of BMSCs and increased the activity of ALP during differentiation of BMSCs, compared with CGRP- or Sr-CPC. Moreover, CGRP-Sr-CPC significantly up-regulated the expression levels of osteogenic differentiation-related genes including Alp, Bmp2, Osteonectin and Runx2 during differentiation.

Conclusions: These findings demonstrate the optimized effects of CGRP- and Sr-enriched CPC in promoting proliferation and osteogenic differentiation of BMSCs, suggesting the potential ability of this novel cement to assist the formation of new bone during osteoporosis-induced bone disorders.

MeSH terms

  • Animals
  • Bone Cements / chemistry
  • Bone Cements / pharmacology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Calcitonin Gene-Related Peptide / chemistry
  • Calcitonin Gene-Related Peptide / pharmacology*
  • Calcium Phosphates / chemistry
  • Calcium Phosphates / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Female
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Rats
  • Strontium / chemistry
  • Strontium / pharmacology*

Substances

  • Bone Cements
  • Calcium Phosphates
  • calcium phosphate
  • Calcitonin Gene-Related Peptide
  • Strontium