Department of Orthopedics, The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan Ave. West, Guangzhou, 510630, P.R. China.
Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond Street, London, ON N6A 5C1, Canada.
Sci Rep. 2018 Feb 12;8(1):2855. doi: 10.1038/s41598-018-21184-5.
To examine the early changes of articular cartilage and subchondral bone in the DMM mouse model of osteoarthritis, mice were subjected to DMM or SHAM surgery and sacrificed at 2-, 5- and 10-week post-surgery. Catwalk gait analyses, Micro-Computed Tomography, Toluidine Blue, Picrosirius Red and Tartrate-Resistant Acid Phosphatase (TRAP) staining were used to investigate gait patterns, joint morphology, subchondral bone, cartilage, collagen organization and osteoclasts activity, respectively. Results showed OA progressed over 10-week time-course. Gait disparity occurred only at 10-week post-surgery. Osteophyte formed at 2-week post-surgery. BMDs of DMM showed no statistical differences comparing to SHAM at 2 weeks, but BV/TV is much higher in DMM mice. Increased BMD was clearly found at 5- and 10-week post-surgery in DMM mice. TRAP staining showed increased osteoclast activity at the site of osteophyte formation of DMM joints at 5- and 10-week time points. These results showed that subchondral bone turnover might occurred earlier than 2 weeks in this mouse DMM model. Gait disparity only occurred at later stage of OA in DMM mice. Notably, patella dislocation could occur in some of the DMM mice and cause a different pattern of OA in affected knee.
为了研究骨关节炎 DMM 小鼠模型中关节软骨和软骨下骨的早期变化,将小鼠进行 DMM 或 SHAM 手术,并在手术后 2、5 和 10 周时处死。步态分析、Micro-CT、甲苯胺蓝、苦味酸天狼猩红和抗酒石酸酸性磷酸酶(TRAP)染色分别用于研究步态模式、关节形态、软骨下骨、软骨、胶原组织和破骨细胞活性。结果表明,OA 在 10 周的时间过程中进展。只有在手术后 10 周才出现步态差异。骨赘在手术后 2 周形成。与 2 周时的 SHAM 相比,DMM 中的 BMD 在统计学上没有差异,但 DMM 小鼠的 BV/TV 更高。在 5 周和 10 周时,DMM 小鼠的 BMD 明显增加。TRAP 染色显示,在 5 周和 10 周时,DMM 关节骨赘形成部位的破骨细胞活性增加。这些结果表明,在这种 DMM 小鼠模型中,软骨下骨转换可能早于 2 周发生。在 DMM 小鼠中,步态差异仅出现在 OA 的晚期。值得注意的是,一些 DMM 小鼠可能会发生髌骨脱位,并导致受影响的膝关节出现不同模式的 OA。