Time-dependent loss of mitochondrial function precedes progressive histologic cartilage degeneration in a rabbit meniscal destabilization model.
Time-dependent loss of mitochondrial function precedes progressive histologic cartilage degeneration in a rabbit meniscal destabilization model.
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DOI：
10.1002/jor.23327
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发表时间：
2017-03
影响因子：
2.8
通讯作者：
Tochigi, Yuki
中科院分区：
文献类型：
--
作者：
Goetz, Jessica E.;Coleman, Mitchell C.;Fredericks, Douglas C.;Petersen, Emily;Martin, James A.;McKinley, Todd O.;Tochigi, Yuki
这项工作的目标是表征兔内侧半月板不稳定 (MMD) 模型中骨关节炎软骨退变的进展，然后使用该模型来识别在体内长期升高的关节接触应力下软骨细胞代谢的组织前破坏。为了表征 PTOA 进展，24 只兔子接受了 MMD 或假手术。使用 Tekscan 压敏走道在术前和术后定期分析肢体负荷。术后 8 周（n=8 MMD；n=8 假手术）或 26 周（n=8 MMD）对动物实施安乐死，通过客观、半自动 Mankin 评分程序进行组织学软骨评估。为了检查组织学前的病理学，对另外 20 只兔子进行了 MMD，并在术后 1 周 (n=9) 或 4 周 (n=10) 处死。新鲜收获软骨细胞用于测量线粒体功能，线粒体功能是机械损伤后病理学的细胞内指标。 MMD 和假手术均导致肢体负荷略有下降，两周后恢复至术前水平。 MMD 后 8 周至 26 周，组织学上明显的软骨损伤进展。软骨细胞呼吸的变化在 1 周时有所不同，但到术后 4 周时，软骨细胞线粒体功能显着降低。许多导致 PTOA 的人体损伤相对较轻，导致疾病的细胞水平机制仍不清楚。我们记录了持续使用下轻微关节损伤的动物模型中 PTOA 的进展，并证明该模型为研究在明显组织变性之前发生的多阶段细胞病理学提供了现实的环境，并且可以作为疾病修饰治疗的目标。
The goals of this work were to characterize progression of osteoarthritic cartilage degeneration in a rabbit medial meniscus destabilization (MMD) model and then to use the model to identify pre-histologic disruptions in chondrocyte metabolism under chronically elevated joint contact stresses in vivo. To characterize PTOA progression, 24 rabbits received either MMD or sham surgery. Limb loading was analyzed preoperatively and at regular postoperative intervals using a Tekscan pressure-sensitive walkway. Animals were euthanized 8 (n=8 MMD; n=8 sham) or 26 weeks (n=8 MMD) postoperatively for histological cartilage evaluation by an objective, semiautomated Mankin scoring routine. To examine pre-histologic pathology, MMD was performed on an additional 20 rabbits, euthanized one (n=9) or four weeks (n=10) postoperatively. Chondrocytes were harvested fresh for measurement of mitochondrial function, an intracellular indicator of pathology after mechanical injury. Both MMD and sham surgery caused slight decreases in limb loading which returned to preoperative levels after 2 weeks. Histologically apparent cartilage damage progressed from 8 to 26 weeks after MMD. Changes in chondrocyte respiration were variable at 1 week, but by 4 weeks postoperatively chondrocyte mitochondrial function was significantly reduced. Many human injuries that lead to PTOA are relatively mild, and the cell-level mechanisms leading to disease remain unclear. We have documented PTOA progression in an animal model of subtle joint injury under continued use, and demonstrated that this model provides a realistic environment for investigation of multi-stage cellular pathology that develops prior to overt tissue degeneration and which could be targeted for disease modifying treatments.
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DOI：
10.1016/j.arthro.2012.03.015
发表时间：
2012-10-01
影响因子：
4.7
作者：
Brophy, Robert H.;Martinez, Mario;Silva, Matthew J.
通讯作者：
Silva, Matthew J.
影响因子：
--
作者：
Safayi, S.;Miller, J. W.;Howard, M. A., III
通讯作者：
Howard, M. A., III
影响因子：
7
作者：
Julkunen, P.;Harjula, T.;Helminen, H. J.
通讯作者：
Helminen, H. J.
影响因子：
27.4
作者：
Ostergaard, K;Andersen, CB;Salter, DM
通讯作者：
Salter, DM
DOI：
10.1002/art.39460
发表时间：
2016-03
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Coleman MC;Ramakrishnan PS;Brouillette MJ;Martin JA
通讯作者：
Martin JA