Brimmo Olubusola A, Pfeiffer Ferris, Bozynski Chantelle C, Kuroki Keiichi, Cook Cristi, Stoker Aaron, Sherman Seth L, Monibi Farrah, Cook James L
Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri.
Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri.
J Knee Surg. 2016 Apr;29(3):235-41. doi: 10.1055/s-0035-1549026. Epub 2015 Apr 18.
Translational models of posttraumatic osteoarthritis (PTOA) that accurately represent clinical pathology need to be developed. This study assessed a novel canine model for PTOA using impact injury. Impacts were delivered to the medial femoral condyle of dogs using a custom-designed impactor at 20, 40, or 60 MPa. Functional assessments and magnetic resonance imaging (MRI) were performed at 2 and 12 weeks, and arthroscopic and histologic assessments were performed at 12 weeks after injury. At 2 and 12 weeks, dogs had observable lameness, knee pain, effusion, loss in range of motion (ROM) and dysfunction in both hindlimbs with severity correlated strongly (r > 0.77) to impact level. At 12 weeks, function, pain, effusion, and ROM were significantly (p < 0.049) worse in knees impacted at 40 and 60 MPa compared with 20 MPa. MRI showed consistent cartilage and subchondral bone marrow lesions, and arthroscopy revealed synovitis and cartilage destruction in impacted knees, with increased severity for 40 and 60 MPa impacts. Histopathology was significantly (p = 0.049) more severe in 40 and 60 MPa and strongly correlated (r = 0.93) to impact level. This novel translational model appears to be valid for investigation of PTOA, including determination of temporal mechanisms of disease and preclinical testing for preventative and therapeutic strategies.
需要开发能够准确反映临床病理的创伤后骨关节炎(PTOA)转化模型。本研究评估了一种使用撞击损伤的新型犬类PTOA模型。使用定制设计的撞击器以20、40或60兆帕的压力撞击犬的内侧股骨髁。在损伤后2周和12周进行功能评估和磁共振成像(MRI),并在12周时进行关节镜检查和组织学评估。在2周和12周时,犬出现明显跛行、膝关节疼痛、积液、活动范围(ROM)丧失以及双后肢功能障碍,严重程度与撞击水平密切相关(r>0.77)。在12周时,与20兆帕的撞击相比,40和60兆帕撞击的膝关节在功能、疼痛、积液和ROM方面明显更差(p<0.049)。MRI显示出一致的软骨和软骨下骨髓损伤,关节镜检查发现撞击膝关节有滑膜炎和软骨破坏,40和60兆帕撞击的严重程度增加。组织病理学在40和60兆帕时明显更严重(p = 0.049),且与撞击水平密切相关(r = 0.93)。这种新型转化模型似乎对PTOA的研究有效,包括确定疾病的时间机制以及预防性和治疗性策略的临床前测试。