Faculty of Dentistry, Thammasat University, Pathumthani, Thailand.
J Oral Pathol Med. 2021 Feb;50(2):191-199. doi: 10.1111/jop.13120. Epub 2021 Jan 8.
Alendronate (ALN) is a bisphosphonate, which is prescribed as an anti-osteoporotic drug. ALN has been shown to increase osteoblast cell death and decrease bone mineralization. ALN inhibits a key regulatory enzyme in the mevalonate pathway, consequently reducing geranylgeranyl pyrophosphate (GGPP). Geranylgeraniol (GGOH) can be converted to GGPP. The aim of this study was to investigate the effects of exogenous GGOH on MC3T3 cell viability, cell cycle, osteoblast function, and cell cytoskeleton under ALN treatment.
MC3T3 cells and osteoblast precursors, were incubated with ALN (0-50 µmol/L) and GGOH (0-50 µmol/L). After treatment, cells were evaluated for cell viability, cell cycle, osteoblast function, and cell cytoskeleton by MTT, flow cytometry, alizarin red S assay, and fluorescent microscopy, respectively.
ALN reduced cell viability and bone nodule formation in a dose-dependent manner. GGOH partially inhibited the negative effects of ALN on cell viability and function. ALN increased the percentages of cell apoptosis and necrosis and arrested cells in G2M phase. Co-incubation with GGOH partially reduced late cell apoptosis and rescued cell cycle arrest. Furthermore, ALN altered MC3T3 morphology and decreased cell area, actin stress fiber density as well as nuclear area. GGOH abolished the effect of ALN on cell area, actin stress fiber density, and nuclear area.
GGOH partially inhibited negative effects of ALN on cell viability, cell cycle, function, and cell cytoskeleton. It might be an additional option for increasing osteoblast function and reducing apoptosis of osteoblasts in the condition treated with low bisphosphonate concentration.
阿仑膦酸钠（ALN）是一种双膦酸盐，被开为抗骨质疏松药物。研究表明，ALN 会增加成骨细胞的死亡并减少骨矿化。ALN 抑制了法呢醇焦磷酸合酶途径中的关键调节酶，从而减少了香叶基香叶基焦磷酸（GGPP）的产生。香叶基醇（GGOH）可以转化为 GGPP。本研究旨在探讨外源性 GGOH 在 ALN 处理下对 MC3T3 细胞活力、细胞周期、成骨细胞功能和细胞细胞骨架的影响。
将 MC3T3 细胞和成骨细胞前体与 ALN（0-50μmol/L）和 GGOH（0-50μmol/L）孵育。处理后，通过 MTT、流式细胞术、茜素红 S 测定和荧光显微镜分别评估细胞活力、细胞周期、成骨细胞功能和细胞细胞骨架。
ALN 呈剂量依赖性降低细胞活力和骨结节形成。GGOH 部分抑制了 ALN 对细胞活力和功能的负性作用。ALN 增加了细胞凋亡和坏死的比例，并使细胞停滞在 G2M 期。与 GGOH 共孵育部分减少了晚期细胞凋亡并挽救了细胞周期停滞。此外，ALN 改变了 MC3T3 的形态并减少了细胞面积、肌动蛋白应力纤维密度和核面积。GGOH 消除了 ALN 对细胞面积、肌动蛋白应力纤维密度和核面积的影响。
GGOH 部分抑制了 ALN 对细胞活力、细胞周期、功能和细胞细胞骨架的负性作用。它可能是增加低浓度双膦酸盐处理条件下成骨细胞功能和减少成骨细胞凋亡的另一种选择。
