STIM1 expression is associated with osteosarcoma cell survival

Objective: To examine the role of store-operated calcium entry(SOCE) and stromal interaction molecule 1(STIM1) in survival and migration of osteosarcoma cells and investigate what blockade of store-operated Ca^(2+)contributes to the regulation of osteosarcoma cells.Methods: First, we examined the expression levels of STIM1 in osteosarcoma cell lines by Western analysis and in tissue specimens by immunohistochemistry. Second, we investigated the effect of SOCE and STIM1 on osteosarcoma cell viability using MTS assays and on cell proliferation using colony formation. Third, we investigated the role of SOCE and STIM1 in cell migration using wound healing assays and Boyden chamber assays. Finally, we studied the effect of SOCE on the nuclear factor of activated T-cells cytoplasmic 1(NFATc1)activity by luciferase assays.Results: STIM1 was overexpressed in osteosarcoma cell lines and tissue specimens and was associated with poor survival of osteosarcoma patients. Also, inhibition of SOCE and STIM1 decreased the cell viability and migration of osteosarcoma cells. Furthermore, our results showed that blockade of store-operated Ca^(2+) channels involved down-regulation of NFATc1 in osteosarcoma cells.Conclusions: STIM1 is essential for osteosarcoma cell functions, and STIM1 and Ca^(2+) entry pathway could be further explored as molecular targets in the treatment of osteosarcoma.

Amorphous calcium magnesium phosphate nanocomposites with superior osteogenic activity for bone regeneration

The seek of bioactive materials for promoting bone regeneration is a challenging and longterm task.Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials.Herein,amorphous calcium magnesium phosphate(ACMP)nanoparticles and simvastatin(SIM)-loaded ACMP(ACMP/SIM)nanocomposites were developed via a simple co-precipitation strategy.The physiochemical property of ACMP/SIM was explored using transmission electron microscope(TEM),Fourier transform infrared spectroscopy(FTIR),powder X-ray diffraction(XRD)and highperformance liquid chromatograph(HPLC),and the role of Mg^(2+) in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure(XANES).After that,the transformation process of ACMP/SIM in simulated body fluid(SBF)was also tracked to simulate and explore the in vivo mineralization performance of materials.We find that ACMP/SIM releases ions of Ca^(2+),Mg^(2+)and PO_(4)^(3),when it is immersed in SBF at 37℃,and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite(HAP).Furthermore,ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells.For the in vivo studies,lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria.ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12weeks.The bioactive ACMP/SIM nanocomposites are promising as bone repair materials.Considering the facile preparation process and superior in vitro/vivo bioactivity,the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.