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.

中文翻译：

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TiAl6V4颗粒对人骨髓间充质干细胞成骨潜能的浓度依赖性调节。

全关节置换是骨关节炎最有效的治疗方法之一，而人工关节的无菌性松动是导致关节置换失败的主要并发症。关于钛合金颗粒对间充质干细胞成骨分化影响的研究非常有限。在这项研究中，人类骨髓源间充质干细胞（BM-hMSCs）用不同浓度的TiAl6V4颗粒处理。通过MTT测定法检测细胞活力，并通过CKK-8测定法评估细胞增殖。成骨分化的早期和晚期通过碱性磷酸酶（ALP）和茜素红S（ARS）染色测定来确定。通过RT-PCR和Western blot分析成骨基因和蛋白的表达。高浓度的TiAl6V4颗粒100μg/ ml抑制了BM-hMSCs的细胞活力。但是，TiAl6V4在5-50μg/ ml的范围内，对BM-hMSCs的细胞活力和细胞增殖均无影响。TiAl6V4颗粒对BM-hMSC成骨表现出浓度依赖性的双向调控。具体而言，5μg/ ml的TiAl6V4促进了BM-hMSC的成骨作用，而50μg/ ml的TiAl6V4抑制了这一现象。此外，机理研究表明，TiAl6V4对BM-hMSCs的调控与Wnt信号通路有关。考虑到间充质细胞的潜力，我们的研究表明，尽量减少使用金属是减少关节置换失败的诱人策略。TiAl6V4在5-50μg/ ml的范围内对BM-hMSCs的细胞活力和细胞增殖均无影响。TiAl6V4颗粒对BM-hMSC成骨表现出浓度依赖性的双向调控。具体而言，5μg/ ml的TiAl6V4促进了BM-hMSC的成骨作用，而50μg/ ml的TiAl6V4抑制了这一现象。此外，机理研究表明，TiAl6V4对BM-hMSCs的调控与Wnt信号通路有关。考虑到间充质细胞的潜力，我们的研究表明，尽量减少使用金属是减少关节置换失败的诱人策略。TiAl6V4在5-50μg/ ml的范围内对BM-hMSCs的细胞活力和细胞增殖均无影响。TiAl6V4颗粒对BM-hMSC成骨表现出浓度依赖性的双向调控。具体而言，5μg/ ml的TiAl6V4促进了BM-hMSC的成骨作用，而50μg/ ml的TiAl6V4抑制了这一现象。此外，机理研究表明，TiAl6V4对BM-hMSCs的调控与Wnt信号通路有关。考虑到间充质细胞的潜力，我们的研究表明，尽量减少使用金属是减少关节置换失败的诱人策略。它被50μg/ ml的TiAl6V4抑制。此外，机理研究表明，TiAl6V4对BM-hMSCs的调控与Wnt信号通路有关。考虑到间充质细胞的潜力，我们的研究表明，尽量减少使用金属是减少关节置换失败的诱人策略。它被50μg/ ml的TiAl6V4抑制。此外，机理研究表明，TiAl6V4对BM-hMSCs的调控与Wnt信号通路有关。考虑到间充质细胞的潜力，我们的研究表明，尽量减少使用金属是减少关节置换失败的诱人策略。