Abstract：
Preclinical models of osteochondral defects (OCDs) are fundamental test beds to evaluate treatment modalities before clinical translation. To increase the rigor and reproducibility of translational science for a robust \"go or no-go,\" we evaluated disease progression and pain phenotypes within the whole joint for two OCD rat models with same defect size (1.5 x 0.8 mm) placed either in the trochlea or medial condyle of femur. Remarkably, we only found subtle transitory changes to gaits of rats with trochlear defect without any discernible effect to allodynia. At 8-weeks post-surgery, anatomical evaluations of joint showed early signs of osteoarthritis with EPIC-microCT. For the trochlear defect, cartilage attenuation was increased in trochlear, medial, and lateral compartments of the femur. For condylar defect, increased cartilage attenuation was isolated to the medial condyle of the femur. Further, the medial ossicle showed signs of deterioration as indicated with decreased bone mineral density and increased bone surface area to volume ratio. Thus, OCD in a weight-bearing region of the femur gave rise to more advanced osteoarthritis phenotype within a unilateral joint compartment. Subchondral bone remodeling was evident in both models without any indication of closure of the articular cartilage surface. We conclude that rat OCD, placed in the trochlear or condylar region of the femur, leads to differing severity of osteoarthritis progression. As found herein, repair of the defect with fibrous tissue and subchondral bone is insufficient to alleviate onset of osteoarthritis. Future therapies using rat OCD model should address joint osteoarthritis in addition to repair itself.
摘要：
骨软骨缺损（OCD）的临床前模型是在临床转化之前评估治疗方式的基本测试床。为了提高转化科学的严谨性和可重复性，以实现健壮的“走或不走”，“我们评估了两种OCD大鼠模型在整个关节内的疾病进展和疼痛表型，这些模型具有相同的缺损大小（1.5x0.8mm），放置在股骨滑车或内侧髁中。值得注意的是,我们只发现有滑车缺损的大鼠步态有细微的短暂变化，对异常性疼痛没有任何明显的影响。手术后8周,通过EPIC-microCT对关节的解剖评估显示骨关节炎的早期征象。对于滑车缺陷，滑车软骨衰减增加，中间,和股骨的外侧隔室。对于髁突缺损,增加的软骨衰减被隔离到股骨内侧髁。Further,内侧小骨显示出恶化的迹象，如骨矿物质密度降低和骨表面积与体积比增加所示。因此，股骨负重区域的OCD在单侧关节室中引起更高级的骨关节炎表型。在两种模型中，软骨下骨重塑都很明显，没有任何关节软骨表面闭合的迹象。我们得出结论，大鼠强迫症，放置在股骨的滑车或髁区，导致不同严重程度的骨关节炎进展。如本文所述，用纤维组织和软骨下骨修复缺损不足以缓解骨关节炎的发作。使用大鼠OCD模型的未来疗法除了自身修复外，还应解决关节骨关节炎。
