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

Abstract

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). 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. 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. 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.