Abstract
Knee injury often triggers post-traumatic osteoarthritis (PTOA) that affects articular cartilage (AC), subchondral bone, meniscus and the synovial membrane. The available treatments for PTOA are largely ineffective due to late diagnosis past the “treatment window”. This study aimed to develop a detailed understanding of the time line of the progression of PTOA in murine models through longitudinal observation of the femorotibial joint from the onset of the disease to the advanced stage. Quantitative magnetic resonance microimaging (µMRI) and histology were used to evaluate PTOA-associated changes in the knee joints of rats subjected to knee meniscectomy. Systematic longitudinal changes in the articular cartilage thickness, cartilage T2 and the T2 of epiphysis within medial condyles of the tibia were all found to be associated with the development of PTOA in the animals. The following pathogenesis cascade was found to precede advanced PTOA: meniscal injury → AC swelling → subchondral bone remodelling → proteoglycan depletion → free water influx → cartilage erosion. Importantly, the imaging protocol used was entirely MRI-based. This protocol is potentially suitable for whole-knee longitudinal, non-invasive assessment of the development of OA. The results of this work will inform the improvement of the imaging methods for early diagnosis of PTOA.
Highlights
A common consequence of joint injury is post-traumatic osteoarthritis (PTOA), which accounts for 12% of all cases of osteoarthritis (OA)[1]
The femoral and tibial articular cartilage (AC) were in direct contact in the central slice, which contained the largest cross-section of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL)
This study investigated the development of PTOA in a rat model where the disease was induced by complete removal of medial meniscus or meniscectomy[16]
Summary
A common consequence of joint injury is post-traumatic osteoarthritis (PTOA), which accounts for 12% of all cases of osteoarthritis (OA)[1]. We investigated the progression of PTOA in rat knee joints that underwent meniscectomy (MSX), a standard protocol for PTOA initiation known to replicate human PTOA with a significant degree of similarity[16,17] The use of this model has eliminated the variabilities due to age, weight, genetics, and environmental conditions that may result in a significant variability of the clinical manifestation of the disease. The whole knee joints were monitored weekly over an eight-week post-injury time window in order to capture the gradual developmental changes from very early PTOA preceding to the severe stage. The objectives of the present study were (1) to enhance the analytical capabilities of quantitative MRI for early detection of PTOA and (2) to identify the sequential changes in tibial tissues leading from the initial knee injury towards advanced PTOA
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