BACKGROUND Bone mineral density of the humeral head is an independent determining factor for postoperative rotator cuff tendon healing. Bisphosphonates, which are commonly used to treat osteoporosis, have raised concerns regarding their relationships to osteonecrosis of the jaw and to atypical fracture of the femur. In view of the prevalence of rotator cuff tear in osteoporotic elderly people, it is important to determine whether bisphosphonates affect rotator cuff tendon healing. However, no studies have investigated bisphosphonates' cytotoxicity to human rotator cuff tendon fibroblasts (HRFs) or bisphosphonates' effects on rotator cuff tendon healing. The purpose of this study was to evaluate the cytotoxicity of alendronate (Ald), a bisphosphonate, and its effects on HRF wound healing. METHODS HRFs were obtained from human supraspinatus tendons, using primary cell cultures. The experimental groups were control, 0.1 μM Ald, 1 μM Ald, 10 μM Ald, and 100 μM Ald. Alendronate exposure was for 48 h, except during a cell viability analysis with durations from 1 day to 6 days. The experimental groups were evaluated for cell viability, cell cycle and cell proliferation, type of cell death, caspase activity, and wound-healing ability. RESULTS The following findings regarding the 100 μM Ald group contrasted with those for all the other experimental groups: a significantly lower rate of live cells (p < 0.01), a higher rate of subG1 population, a lower rate of Ki-67 positive cells, higher rates of apoptosis and necrosis, a higher number of cells with DNA fragmentation, higher caspase-3/7 activity (p < 0.001), and a higher number of caspase-3 positive staining cells. In scratch-wound healing analyses of all the experimental groups, all the wounds healed within 48 h, except in the 100 μM Ald group (p < 0.001). CONCLUSIONS Low concentrations of alendronate appear to have little effect on HRF viability, proliferation, migration, and wound healing. However, high concentrations are significantly cytotoxic, impairing cellular proliferation, cellular migration, and wound healing in vitro.

中文翻译：

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阿仑膦酸盐对人肩袖肌腱成纤维细胞的体外作用。

背景技术肱骨头的骨矿物质密度是术后肩袖肌腱愈合的独立决定因素。通常用于治疗骨质疏松症的双膦酸盐引起了人们对其与颌骨坏死和股骨非典型骨折的关系的关注。考虑到骨质疏松老年人的肩袖撕裂患病率，确定双膦酸盐是否影响肩袖腱愈合很重要。但是，尚无研究研究双膦酸盐对人肩袖肌腱成纤维细胞（HRF）的细胞毒性或双膦酸盐对肩袖肌腱愈合的影响。这项研究的目的是评估双膦酸盐阿仑膦酸盐（Ald）的细胞毒性及其对HRF伤口愈合的影响。方法使用原代细胞培养物从人的棘上肌腱中获得HRF。实验组为对照组，0.1μMAld，1μMAld，10μMAld和100μMAld。除在1天至6天的细胞生存力分析期间，阿仑膦酸酯暴露持续48 h。对实验组的细胞活力，细胞周期和细胞增殖，细胞死亡类型，胱天蛋白酶活性和伤口愈合能力进行了评估。结果关于100μMAld组的以下发现与所有其他实验组的发现相反：活细胞的比率显着降低（p <0.01），subG1群体的比率较高，Ki-67阳性细胞的比率较低，细胞凋亡和坏死的发生率更高，DNA断裂的细胞数量更多，胱天蛋白酶3/7活性更高（p <0.001），和更多的caspase-3阳性染色细胞。在所有实验组的刮擦伤口愈合分析中，除100μMAld组外，所有伤口均在48小时内愈合（p <0.001）。结论低浓度的阿仑膦酸盐似乎对HRF的生存力，增殖，迁移和伤口愈合几乎没有影响。但是，高浓度具有明显的细胞毒性，损害细胞增殖，细胞迁移和体外伤口愈合。