Abstract
To examine the early changes of articular cartilage and subchondral bone in the DMM mouse model of osteoarthritis, mice were subjected to DMM or SHAM surgery and sacrificed at 2-, 5- and 10-week post-surgery. Catwalk gait analyses, Micro-Computed Tomography, Toluidine Blue, Picrosirius Red and Tartrate-Resistant Acid Phosphatase (TRAP) staining were used to investigate gait patterns, joint morphology, subchondral bone, cartilage, collagen organization and osteoclasts activity, respectively. Results showed OA progressed over 10-week time-course. Gait disparity occurred only at 10-week post-surgery. Osteophyte formed at 2-week post-surgery. BMDs of DMM showed no statistical differences comparing to SHAM at 2 weeks, but BV/TV is much higher in DMM mice. Increased BMD was clearly found at 5- and 10-week post-surgery in DMM mice. TRAP staining showed increased osteoclast activity at the site of osteophyte formation of DMM joints at 5- and 10-week time points. These results showed that subchondral bone turnover might occurred earlier than 2 weeks in this mouse DMM model. Gait disparity only occurred at later stage of OA in DMM mice. Notably, patella dislocation could occur in some of the DMM mice and cause a different pattern of OA in affected knee.
Highlights
Osteoarthritis (OA) is a prevalent musculoskeletal disease that causes pain and disability for millions of people
Regional proteoglycan loss and chondrocyte clustering occurred on the medial compartments of the joint at 2 weeks post-surgery, especially the medial tibial plateau (MTP) (Fig. 2A,b, white arrow)
Cartilaginous tissue formed on the medial edge of tibia and stained strongly with toluidine blue (TB) at 2-week time-point in DMM mice (Fig. 2A,b, black arrow), with collagen fibril organization similar to that of articular cartilage (Fig. 2A,d, white arrow). 5 weeks post-surgery, mild to moderate cartilage damage can be found in the surgical joints of DMM mice
Summary
Osteoarthritis (OA) is a prevalent musculoskeletal disease that causes pain and disability for millions of people It is characterized by progressive cartilage erosion, subchondral bone turnover and osteophyte formation, amongst other pathological alterations within the joint. Box 5015, 100 Perth Drive, London, ON N6A 5K8, Canada This DMM model and found age and gender matter in articular cartilage and subchondral bone changes after surgery[7]. Subchondral bone changes during the time-course of the disease in the DMM model have not been characterized in detail This current study aims to examine the early changes of articular cartilage, subchondral bone and their progressions in the DMM model, as well as other parameters of OA including standard histology and gait pattern alterations
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