Concentration-Dependent Regulation of TiAl₆V₄ Particles on the Osteogenesis Potential of Human Bone Marrow...

Total joint replacement is one of the most effective treatments for osteoarthritis, while the aseptic loosening of artificial joint is a major complication leading to the joint replacement failure. There are very limited studies about the effects of titanium-alloy particles on the osteogenic differentiation of mesenchymal stem cells. In this study, human bone marrow-derived mesenchymal stem cells (BM-hMSCs) were treated with different concentrations of TiAl₆V₄ particles. The cell viability was detected by MTT assay, and the cell proliferation was assessed by CKK-8 assay. The early and late stages of osteogenic differentiation were determined by alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining assays. The expression of osteogenic genes and proteins was analyzed by RT-PCR and Western blot. TiAl₆V₄ particles at high concentration 100 μg/ml inhibited the cell viability of BM-hMSCs. However, TiAl₆V₄ in the range of 5-50 μg/ml did not show effects neither on the cell viability nor on the cell proliferation of BM-hMSCs. TiAl₆V₄ particles showed concentration-dependent bidirectional regulations on BM-hMSC osteogenesis. Specifically, TiAl₆V₄ at 5 μg/ml promoted the osteogenesis of BM-hMSCs, which was suppressed by TiAl₆V₄ at 50 μg/ml. Further, mechanism study revealed that the regulation of TiAl₆V₄ on BM-hMSCs was related to Wnt signaling pathway. Given the potential of mesenchymal cells, our study suggested that the minimization of metal use would be an attractive strategy to reduce the joint replacement failure.