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Sex- and injury-based differences in knee biomechanics in mouse models of post-traumatic osteoarthritis
Journal of Biomechanics ( IF 2.4 ) Pub Date : 2020-11-27 , DOI: 10.1016/j.jbiomech.2020.110152
Carina L. Blaker , Dylan M. Ashton , Nathan Doran , Christopher B. Little , Elizabeth C. Clarke

Sex and joint injury are risk factors implicated in the onset and progression of osteoarthritis (OA). In mouse models of post-traumatic OA (ptOA), the pathogenesis of disease is notably impacted by sex (often worse in males) and injury model (e.g. meniscal versus ligament injury). Increasing ptOA progression and severity is often associated with greater relative instability of the joint but few studies have directly quantified changes in joint mechanics after injury and compared outcomes across multiple models in both male and female mice.

Passive anterior-posterior knee biomechanics were evaluated in 10-week-old, male and female C57BL/6J mice. PtOA injury models included destabilisation of the medial meniscus (DMM), anterior cruciate ligament transection (ACLT) or mechanical rupture (ACLR), and combined DMM and ACLT (DMM + ACLT). Sham operated and non-operated controls (NOC) were included for baseline comparisons. The test apparatus loaded hindlimbs at 60° flexion between ± 1 N at 0.5 mm/s (build specifications available for download: https://doi.org/10.17632/z754455x3c.1). Measures of joint laxity (range of motion, neutral zone) and stiffness were calculated.

Joint laxity was comparable between male and female mice while joint stiffness was greater in females (P ≤ 0.002, correcting for body-mass and injury-model). Anterior-posterior joint mechanics were minimally altered by DMM but significantly affected by loss of the ACL (P < 0.001), with equivalent changes between ACL-injury models despite different injury mechanisms and adjacent meniscal damage. These findings suggest that despite the important role of joint injury; sex- and model-specific differences in ptOA progression and severity are not primarily driven by altered anterior-posterior knee biomechanics.



中文翻译:

创伤后骨关节炎小鼠模型中基于性别和伤害的膝关节生物力学差异

性和关节损伤是与骨关节炎(OA)的发作和发展有关的危险因素。在创伤后OA(ptOA)的小鼠模型中,疾病的发病机理特别受到性别(通常在男性中更为严重)和损伤模型(例如半月板与韧带损伤)的影响。ptOA进展和严重程度的增加通常与关节的相对相对不稳定有关,但是很少有研究直接量化损伤后关节力学的变化,并且在雄性和雌性小鼠中比较了多种模型的结果。

在10周龄的雄性和雌性C57BL / 6J小鼠中评估了被动的前后膝关节生物力学。PtOA损伤模型包括内侧半月板(DMM)不稳定,前交叉韧带横断(ACLT)或机械破裂(ACLR),以及DMM和ACLT合并(DMM + ACLT)。包括假手术和非手术对照(NOC)用于基线比较。测试设备以0.5 mm / s的速度在±1 N之间以60°的挠度加载后肢(可下载构建规格:https://doi.org/10.17632/z754455x3c.1)。计算关节松弛度(运动范围,中性区)和僵硬度的量度。

雄性和雌性小鼠的关节松弛度相当,而雌性小鼠的关节僵硬度更高(P≤0.002,校正了身体质量和损伤模型)。DMM对前-后关节力学的影响很小,但受ACL损失的影响显着(P <0.001),尽管损伤机制和相邻的半月板损伤不同,但ACL损伤模型之间的变化相当。这些发现表明,尽管关节损伤起着重要的作用。ptOA进展和严重程度的性别和模型特定差异并非主要由前后膝关节生物力学改变引起。

更新日期:2020-12-05
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