RESUMEN
Calcium phosphatebased bone substitutes have been widely used for bone repair, augmentation and reconstruction in bone implant surgery. While some of these substitutes have shown excellent biological efficacy, there remains a need to improve the performance of the current calcium phosphatebased bone substitutes. Strontium ions (Sr) can promote new osteogenesis, inhibit osteoclast formation and increase osteoconductivity. However, the therapeutic effect and mechanism of strontiumcontaining αcalcium sulfate hemihydrate (SrCaS) remains unclear. The present study created bone injuries in rats and treated the injuries with SrCaS. Then Cell Counting Kit8, soft agar colony formation, flow cytometry, Transwell and Alizarin Red staining assays were performed to assess the bone cells for their proliferation, growth, apoptosis, invasion, and osteogenic differentiation abilities. The bone reconstructive states were measured by the microCT method, hematoxylin and eosin staining and Masson staining. Bonerelated factors were analyzed by the reverse transcriptionquantitative PCR assay; transforming growth factor (TGF)ß, mothers against decapentaplegic homolog (Smad)2/3 and ßcatenin expression was measured by western blot analysis and osteocalcin (OCN) expression was assessed by immunohistochemistry. SrCaS did not significantly affect the proliferation and apoptosis of bone marrow stem cells (BMSCs), but did accelerate the migration and osteogenic differentiation of BMSCs in vitro. SrCaS promoted bone repair and significantly increased the values for bone mineral density, bone volume fraction, and trabecular thickness, but decreased trabecular spacing in vivo in a concentration-dependent manner. In addition, SrCaS dramatically upregulated the expression levels of genes associated with osteogenic differentiation (Runtrelated transcription factor 2, Osterix, ALP, OCN and bone sialoprotein) both in vitro and in vivo. SrCaS also increased Smad2/3, TGFß and phosphorylatedßcatenin protein expression in vitro and in vivo. These results indicated that materials that contain 5 or 10% Sr can improve bone defects by regulating the TGFß/Smad signaling pathway.