Aim: The purpose of this study was to evaluate whether pharmacologic treatments or genotypes shown to prolong murine lifespan ameliorate the severity of age-associated osteoarthritis.Materials and Methods: Male UM-HET3 mice were fed diets containing 17-α-estradiol, acarbose, nordihydroguaiaretic acid, or control diet per the National Institute on Aging Interventions Testing Program (ITP) protocol. Findings were compared to genetically long-lived male Ames dwarf mice. Stifles were analyzed histologically with articular cartilage structure (ACS) and safranin O scoring as well as with quantitative histomorphometry.Results: Depending on the experimental group, ITP mice were between 450 and 1150 days old at the time of necropsy and 12-15 animals were studied per group. Two age groups (450 and 750 days) with 16-20 animals per group were used for Ames dwarf studies. No differences were found in the ACS or safranin O scores between treatment and control groups in the ITP study. There was high variability in most of the histologic outcome measures. For example, the older UM-HET3 controls had ACS scores of 6.1 ± 5.8 (mean±SD) and Saf O scores of 6.8 ± 5.6. Nevertheless, 17-α-estradiol mice had larger areas and widths of subchondral bone compared to controls, and dwarf mice had less subchondral bone area and width and less articular cartilage necrosis than non-dwarf controls.Conclusions: UM-HET3 mice developed age-related OA but with a high degree of variability and without a significant effect of the tested ITP treatments. High variability was also seen in the Ames dwarf mice but differences in several measures suggested some protection from OA.

中文翻译：

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寿命延长的雄性小鼠自然发生的骨关节炎。

目的：本研究的目的是评估显示延长小鼠寿命的药物治疗或基因型是否能改善与年龄相关的骨关节炎的严重程度。 材料和方法：雄性 UM-HET3 小鼠被喂食含有 17-α-雌二醇、阿卡波糖、去甲二氢愈创木酸，或按照国家老龄化干预测试计划 (ITP) 协议的控制饮食。研究结果与基因寿命长的雄性艾姆斯侏儒小鼠进行了比较。用关节软骨结构 (ACS) 和番红 O 评分以及定量组织形态计量学对膝关节进行组织学分析。 结果：根据实验组，ITP 小鼠在尸检时为 450 至 1150 天，其中 12-15 只动物为每组学习。两个年龄组（450 天和 750 天），每组 16-20 只动物用于艾姆斯矮人研究。在 ITP 研究中，治疗组和对照组之间的 ACS 或番红 O 评分未发现差异。大多数组织学结果指标存在高度可变性。例如，较旧的 UM-HET3 对照的 ACS 分数为 6.1 ± 5.8（平均值 ± SD），Saf O 分数为 6.8 ± 5.6。然而，与对照组相比，17-α-雌二醇小鼠具有更大的软骨下骨面积和宽度，而侏儒小鼠的软骨下骨面积和宽度比非侏儒对照组更少，关节软骨坏死更少。结论：UM-HET3 小鼠发育年龄-相关的 OA，但具有高度的可变性，并且对测试的 ITP 治疗没有显着影响。