Age-dependent Changes in the Articular Cartilage and Subchondral Bone of C57BL/6 Mice after Surgical Destabilization of Medial Meniscus.
Age-dependent Changes in the Articular Cartilage and Subchondral Bone of C57BL/6 Mice after Surgical Destabilization of Medial Meniscus.
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DOI：
10.1038/srep42294
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发表时间：
2017-02-09
影响因子：
4.6
通讯作者：
Song J
中科院分区：
文献类型：
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作者：
Huang H;Skelly JD;Ayers DC;Song J
年龄是骨关节炎（OA）的主要风险因素，但用于评估疾病修饰OA靶点的手术OA小鼠模型（如内侧半月板（DMM）不稳定）通常仅在年轻成年小鼠上进行。本研究探讨了年龄如何影响DMM后小鼠关节的软骨和软骨下骨变化。对4个月（4 M）、12个月（12 M）和19+个月（19 M+）的雄性C57 BL/6小鼠以及12 M和18 M+的雌性小鼠进行DMM。术后2个月，采集手术和未手术对侧膝关节，并使用软骨组织学评分和软骨下骨板厚度和骨赘形成的μCT定量进行评价。DMM后，12 M和19 M+雄性小鼠的软骨糜烂和软骨下骨板厚度大于4 M雄性小鼠。骨赘的大小随年龄增长而呈上升趋势，而19 M+组的骨体积分数显著较高。此外，12 M雌性动物的OA程度比雄性动物轻，表现为软骨降解较少、软骨下骨板硬化较少和骨赘较小。我们的研究结果揭示了DMM后关节软骨和软骨下骨的不同年龄/性别依赖性结构变化，当使用这种手术技术进行转化OA研究时，有助于更周到地选择小鼠年龄/性别。
Age is the primary risk factor for osteoarthritis (OA), yet surgical OA mouse models such as destabilization of the medial meniscus (DMM) used for evaluating disease-modifying OA targets are frequently performed on young adult mice only. This study investigates how age affects cartilage and subchondral bone changes in mouse joints following DMM. DMM was performed on male C57BL/6 mice at 4 months (4 M), 12 months (12 M) and 19+ months (19 M+) and on females at 12 M and 18 M+. Two months after surgery, operated and unoperated contralateral knees were harvested and evaluated using cartilage histology scores and μCT quantification of subchondral bone plate thickness and osteophyte formation. The 12 M and 19 M+ male mice developed more cartilage erosions and thicker subchondral bone plates after DMM than 4 M males. The size of osteophytes trended up with age, while the bone volume fraction was significantly higher in the 19 M+ group. Furthermore, 12 M females developed milder OA than males as indicated by less cartilage degradation, less subchondral bone plate sclerosis and smaller osteophytes. Our results reveal distinct age/gender-dependent structural changes in joint cartilage and subchondral bone post-DMM, facilitating more thoughtful selection of murine age/gender when using this surgical technique for translational OA research.