Furman Bridgette D, Strand Jens, Hembree W Chad, Ward Benjamin D, Guilak Farshid, Olson Steven A
Division of Orthopaedic Surgery, Department of Surgery, Duke University Medical Center, Box 3389, Durham, North Carolina 27710, USA.
J Orthop Res. 2007 May;25(5):578-92. doi: 10.1002/jor.20331.
Posttraumatic arthritis is one of the most frequent causes of disability following joint trauma. The objective of this study was to develop a model of a closed articular fracture in the mouse knee joint to quantify the temporal sequence of joint degeneration in a model of posttraumatic arthritis. Closed intraarticular fractures were created in the tibial plateau of adult mice (C57BL/6) using a computer-controlled materials testing system and a custom-built indenter tip. Tibial plateau fractures were classified and imaged over time using high-resolution digital radiography. Animals were sacrificed at 2, 4, 8, and 50 weeks following fracture, and the experimental and contralateral control limbs were harvested for histology and micro-computed tomography (microCT) analysis. By radiographic analysis, tibial plateau fractures closely resembled clinical fractures. More complex and comminuted fractures correlated to significantly higher fracture energies. Histologic analysis demonstrated progressive joint degeneration as measured by a modified Mankin scale, with fibrillation and loss of proteoglycan in the articular cartilage. Subchondral bone thickening was also observed in experimental joints. The induction of a closed intraarticular fracture of the mouse tibial plateau generated a reproducible and clinically relevant joint injury that progressed to osteoarthritis-like changes by histologic and microCT evaluations. The ability to induce joint degeneration without an osteotomy or open arthrotomy provides a valuable new model for studying the natural sequelae of posttraumatic arthritis. Notably, the use of a murine model will facilitate the use of genetically modified animals for the investigation of specific genes implicated in the pathology of posttraumatic arthritis.
创伤后关节炎是关节创伤后导致残疾的最常见原因之一。本研究的目的是建立小鼠膝关节闭合性关节骨折模型,以量化创伤后关节炎模型中关节退变的时间顺序。使用计算机控制的材料测试系统和定制的压头尖端,在成年小鼠(C57BL/6)的胫骨平台上造成闭合性关节内骨折。使用高分辨率数字放射摄影术对胫骨平台骨折进行分类并随时间成像。在骨折后2、4、8和50周处死动物,收集实验侧和对侧对照肢体进行组织学和显微计算机断层扫描(microCT)分析。通过放射学分析,胫骨平台骨折与临床骨折非常相似。更复杂和粉碎性骨折与显著更高的骨折能量相关。组织学分析显示,通过改良的曼金量表测量,关节出现进行性退变,关节软骨出现原纤维形成和蛋白聚糖丢失。在实验关节中还观察到软骨下骨增厚。小鼠胫骨平台闭合性关节内骨折的诱导产生了一种可重复的、与临床相关的关节损伤,通过组织学和microCT评估发展为骨关节炎样改变。无需截骨术或开放性关节切开术即可诱导关节退变的能力为研究创伤后关节炎的自然转归提供了一个有价值的新模型。值得注意的是,使用小鼠模型将便于使用基因修饰动物来研究与创伤后关节炎病理相关的特定基因。