Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading.
Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading.
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DOI：
10.1002/jor.23204
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
van der Meulen MC
中科院分区：
文献类型：
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作者：
Ko FC;Dragomir CL;Plumb DA;Hsia AW;Adebayo OO;Goldring SR;Wright TM;Goldring MB;van der Meulen MC
我们先前表明，小鼠膝关节的重复循环负荷引起的变化，概括了人类骨关节炎（OA）的特征。通过应用一个单一的负载会话，我们的特点是在软骨下骨和关节软骨的结构和成分的变化的时间进程。我们对成年（26周龄）C57 Bl/6雄性小鼠的左胫骨施加了一次5分钟的载荷，峰值载荷为9.0 N，持续1200个循环。在负荷后0、1和2周收集膝关节。通过组织学、免疫组织化学（caspase-3和组织蛋白酶K）和显微计算机断层扫描分析关节软骨和软骨下骨的变化。在0时，软骨细胞活力或软骨或软骨下骨完整性无明显变化。然而，软骨病理学表现为局部变薄和蛋白多糖损失发生在1和2周后的单次会议的负荷。在1周时，一过性松质骨丢失明显，与破骨细胞数量增加相关。骨丢失在2周时逆转至对照水平。术后1周和2周关节边缘可见纤维和软骨组织形成。我们的研究结果表明，一个单一的会议的非侵入性负荷导致OA样的形态和细胞的变化，关节软骨和软骨下骨的发展。软骨下骨小梁质量和厚度的损失在2周时恢复到对照水平，而软骨变薄和蛋白聚糖损失持续存在。
We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist.