Comparison of joint degeneration and pain in male and female mice in DMM model of osteoarthritis
Comparison of joint degeneration and pain in male and female mice in DMM model of osteoarthritis
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DOI：
10.1016/j.joca.2021.02.007
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发表时间：
2021-04-29
影响因子：
7
通讯作者：
Kim, H. A.
中科院分区：
文献类型：
--
作者：
Hwang, H. S.;Park, I. Y.;Kim, H. A.
目的：虽然女性中放射学和症状性骨关节炎（OA）的患病率较高，但动物实验中更常使用雄性小鼠来探索其发病机制或药物疗效。在这项研究中，我们检查了性别二态性是否会影响内侧半月板（DMM）小鼠模型不稳定中的疼痛和关节退化。方法：对雄性和雌性C57BL/6小鼠的膝盖进行DMM或假手术。通过番红 O 染色评估关节损伤，并使用国际骨关节炎研究协会 (OARSI) 评分系统进行评分。进行冯弗雷毛发、失能和旋转测试来测量关节疼痛。比较了 TRPV1 拮抗剂辣椒西平 (CPZ) 在雄性和雌性小鼠之间的镇痛效果。 结果：组织学和 OARSI 评分分析显示，雄性和雌性 DMM 组均出现软骨退变，并且进展，但在 OA 晚期，雌性小鼠的损伤较轻。与雌性 DMM 小鼠相比，通过机械异常性疼痛测量，雄性 DMM 小鼠的疼痛行为表现时间更长。失能数据显示，CPZ 显着减轻了雄性小鼠 DMM 引起的疼痛，但雌性小鼠则没有。免疫荧光显微镜分析表明，DMM 手术增加了雌性和雄性背根神经节 (DRG) 中 TRPV1 的表达。注射CPZ仅显着抑制雄性小鼠DRG中TRPV1的表达。结论：DMM后雌性和雄性小鼠的关节损伤发展程度相当，但雌性小鼠的关节损伤进展较少。 TRPV1 拮抗剂的疼痛行为和镇痛功效存在细微的性别差异，同时伴随着 TPRV1 的差异调节。 ？ 2021 年由爱思唯尔有限公司代表国际骨关节炎研究协会出版。
Objective: While the prevalence of radiographic and symptomatic osteoarthritis (OA) is higher in women, male mice are more frequently used in animal experiments to explore its pathogenesis or drug efficacy. In this study, we examined whether sexual dimorphism affects pain and joint degeneration in destabilization of the medial meniscus (DMM) mouse model.Methods: DMM or sham surgery was performed on the knee of male and female C57BL/6 mice. Joint damage was assessed by safranin O staining and scored using the Osteoarthritis Research Society International (OARSI) scoring system. Von Frey hair, incapacitance, and rotarod tests were conducted to measure joint pain. The analgesic effect of capsazepine (CPZ), a TRPV1 antagonist, was compared between male and female mice.Results: Histology and OARSI scoring analysis showed that cartilage degeneration developed, and progressed in both male and female DMM groups, however, damage was less severe in females at the late stage of OA. Pain behavior, as measured by mechanical allodynia, was displayed for longer in male DMM mice compared to females. Incapacitance data showed that CPZ significantly reduced DMM-induced pain in male mice but not in female mice. Immunofluorescence microscopy analysis demonstrated that DMM surgery increased the expression of TRPV1 in both female and male dorsal root ganglion (DRG). Injection of CPZ significantly suppressed TRPV1 expression in the DRG of male mice only.Conclusion: Joint damage develops comparably in both female and male mice after DMM although it progresses less in females. There was a subtle sex difference in pain behaviors and analgesic efficacy of a TRPV1 antagonist, which was accompanied by a differential regulation of TPRV1. ? 2021 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.