The effects of zoledronate on the survival and function of human osteoblast-like cells.
The effects of zoledronate on the survival and function of human osteoblast-like cells.
复制标题
DOI：
10.1186/s12891-015-0818-5
复制
发表时间：
2015-11-16
影响因子：
2.3
通讯作者：
Yang TY
中科院分区：
文献类型：
--
作者：
Huang KC;Cheng CC;Chuang PY;Yang TY
延长双膦酸盐治疗可能抑制骨重建的程度，正常的骨修复受损。虽然这种不良副作用通常归因于双膦酸盐对破骨细胞存活和功能的负面影响，但这些对成骨细胞的影响仍不清楚。在目前的研究中，我们假设μM水平的唑来膦酸盐（ZOL）可能对成骨细胞的存活和功能产生负面影响。对人成骨细胞样细胞进行增殖、迁移和分化的体外分析。我们的结果表明，ZOL处理剂量和时间依赖性诱导成骨细胞凋亡后，浓度已达到10 μM（p < 0.001）。ZOL抑制成骨细胞迁移50%的浓度为10 - 15 μM。此外，基质矿化程度呈剂量依赖性降低，但在分泌的I型胶原和骨钙素以及每个活细胞的碱性磷酸酶活性方面，没有伴随的成骨分化抑制。成骨基因表达分析证实，μM水平的ZOL对成骨细胞的成骨分化没有影响。我们得出结论，μM水平的ZOL影响成骨细胞的存活和迁移，但不影响分化。ZOL在μM水平上对骨骼疾病的病理生理学意义需要在未来的研究中进行调查和澄清。本文的在线版本（doi：10.1186/s12891-015-0818-5）包含补充材料，可供授权用户使用。
Prolonged bisphosphonate treatment might suppress bone remodeling to the extent that normal bone repair is impaired. While this adverse side effect is usually ascribed to the negative effects of bisphosphonates on osteoclast survival and function, these effects on osteoblasts are still unclear. In the current study, we hypothesized that zoledronate (ZOL) at the μM level might present negative effects on osteoblast survival and function. In vitro analyses of proliferation, migration and differentiation were performed on human osteoblast-like cells. Our results revealed that ZOL treatment dose- and time-dependently induced apoptosis of osteoblasts after concentrations had reached 10 μM (p < 0.001). The concentrations at which ZOL inhibited osteoblast migration by 50 % were between 10 and 15 μM. Moreover, there was a dose-dependent reduction in the extent of matrix mineralization, but without a concomitant inhibition of osteogenic differentiation in terms of secreted type I collagen and osteocalcin and of alkaline phosphatase activity per viable cell. Analyses of the expression of osteogenic genes confirmed that ZOL at the μM level had no effects on osteogenic differentiation of osteoblasts. We concluded that ZOL at the μM level affected osteoblast survival and migration, but did not affect differentiation. The pathophysiological implications of ZOL at the μM level on skeletal disorders need to be investigated and clarified in the future researches. The online version of this article (doi:10.1186/s12891-015-0818-5) contains supplementary material, which is available to authorized users.