Meniscus Induced Cartilaginous Damage and Non-linear Gross Anatomical Progression of Early-stage Osteoarthritis in a Canine Model

Abstract

Background:The predictable outcome of the anterior cruciate ligament transection (ACLT) canine model, and the similarity to naturally occurring osteoarthritis (OA) in humans, provide a translatable method for studying OA. Still, evidence of direct meniscus-induced cartilaginous damage has not been identified, and gross-anatomical blinded scoring of early-stage OA has not been performed.Objective:A gross anatomical observation and statistical analysis of OA progression to determine meniscus induced cartilaginous damage, to measure the macroscopic progression of OA, and to address matters involving arthroscopic and surgical procedures of the knee.Method:Unblinded assessment and blinded scoring of meniscal, tibial, femoral, and patellar damage were performed for control and at four time points following unilateral ACLT: 3-week (N=4), 8-week (N=4), 12-week (N=5), and 25-week (N=4). Mixed-model statistics illustrates damage (score) progression; Wilcoxon rank-sum tests compared time-point scores; and Wilcoxon signed-rank tests compared ACLT and contralateral scores, and meniscus and tibia scores.Result:Damage was manifest first on the posterior aspect of the medial meniscus and subsequently on the tibia and femur, implying meniscal damage can precede, coincide with, and aggravate cartilage damage. Damage extent varied chronologically and was dependent upon the joint component. Meniscal damage was evident at 3 weeks and progressed through 25-weeks. Meniscal loose bodies corresponded to tibial cartilage damage location and extent through 12 weeks, followed by cartilage repair activity after complete meniscal degeneration.Conclusion:This study provides additional information for understanding OA progression, identifying OA biomarkers, and arthroscopic and meniscectomy procedures.

Long-term outcome and progression of osteoarthritis in uncomplicated cases of cranial cruciate ligament rupture treated by tibial plateau leveling osteotomy in dogs

“…In particular, the patellar apex consistently showed the highest OAS value among the 15 sites from the preoperative period to 36 months postoperatively. Kahn et al reported that dogs euthanized 3 weeks after CrCL resection had developed damage of the femur and tibial cartilage that contacted the caudal horn of the MM, and osteophytosis at the patellar apex [ 21 ]. Additionally, osteophytosis at the cranial aspect of the stifle joint, such as osteophytosis at the patella and femoral trochlea, reportedly limits the extension of the stifle after TPLO [ 28 ].…”

The Importance of the Knee Joint Meniscal Fibrocartilages as Stabilizing Weight Bearing Structures Providing Global Protection to Human Knee-Joint Tissues

“…This demonstrated the involvement of meniscal pathology in OA development and its contribution to global joint disease [20]. Meniscus induced cartilaginous damage has also been shown to result in anatomical progression of early-stage OA in a canine model [43] emphasising the importance of meniscal pathobiology in global knee joint integrity [3]. Furthermore, targeted mutation of NOV/CCN3 in mice disrupts joint homeostasis and can induce OA-like symptoms [44].…”

“…These studies are insightful as to different forms of OA which develop following meniscal or ligament injury [66]. The use of animal meniscal models [43,67,68,69,70] have also contributed significantly to a greater understanding of the pathobiology of meniscal degeneration and traumatic meniscal injury and may aid in the formulation of therapeutic interventions on these meniscal tissues [71,72].…”

“…Many reviews have emphasized the great potential of MSCs for meniscal repair applications [25,31,36,40,42,43,45,71]. MSCs have been employed in numerous strategies aimed to promote repair of meniscal lacerations [23] and defects in the avascular inner meniscal zone [39,89,90,91] or in meniscal replacement in meniscectomised animals [83].…”

Image interpolation improves the zonal analysis of cartilage T2 relaxation in MRI

“…These canine joints belonged to a multidisciplinary study of the OA progression in our lab, which were approved by the Canadian Council on Animal Care (CCAC). Recently, a blind study of the gross anatomic disease progression in these canine joints has been completed (26). Using the OARSI scores of 0-4 that graded different parts of a joint (27), the 12-week contralateral tibias had a score of 1, while the 12-week transected tibias (OA) had a score of 2; the difference was statistical significant.…”