Abstract
Post-traumatic knee osteoarthritis is characterized by cartilage degeneration, subchondral bone remodeling, osteophyte formation, and synovial changes. Therapeutic targeting of inflammatory activity in the knee immediately post injury may alter the course of osteoarthritis development. This study aimed to determine whether CD200R1 agonists, namely the protein therapeutic CD200Fc or the synthetic DNA aptamer CCS13, both known to act as anti-inflammatory agents, are able to delay the pathogenesis of injury-associated knee osteoarthritis in a murine model. Ten week old male C57BL/6 mice were randomized and surgical destabilization of the medial meniscus (DMM) to induce knee arthritis or sham surgery as a control were performed. CCS13 was evaluated as a therapeutic treatment along with CD200Fc and a phosphate-buffered saline vehicle control. Oligonucleotides were injected intra-articularly beginning one week after surgery, with a total of six injections administered prior to sacrifice at 12 weeks post-surgery. Histopathological assessment was used as the primary outcome measure to assess cartilage and synovial changes, while µCT imaging was used to compare the changes to the subchondral bone between untreated and treated arthritic groups. We did not find any attenuation of cartilage degeneration or synovitis in DMM mice with CD200Fc or CCS13 at 12 weeks post-surgery, nor stereological differences in the properties of subchondral bone. The use of CD200R1 agonists to blunt the inflammatory response in the knee are insufficient to prevent disease progression in the mouse DMM model of OA without anatomical restoration of the normal joint biomechanics.
Highlights
Post-traumatic knee osteoarthritis is a prevalent musculoskeletal disease leading to significant disability with enormous medical and socioeconomic consequences
The objective of this work was to determine whether the CD200R1 agonist aptamer CCS13 or a natural dimeric form of the CD200R1 ligand, namely, CD200Fc can delay the pathogenesis of injury-associated osteoarthritis in a murine model
No significant differences were seen between destabilization of the medial meniscus (DMM)+SHAM and DMM+CD200Fc or DMM+SHAM and DMM+CCS13 (Figure 4B). This is the first study to assess the therapeutic potential of the CD200-CD200R1 pathway in osteoarthritis
Summary
Post-traumatic knee osteoarthritis is a prevalent musculoskeletal disease leading to significant disability with enormous medical and socioeconomic consequences. It is characterized by articular cartilage degeneration, subchondral bone remodeling, osteophyte formation, and synovial changes, including inflammation. Arthritic changes begin in the acute phase post-insult and progress ominously to symptomatic osteoarthritis [1, 2]. With the goal of reducing the risk of osteoarthritis, surgery to optimize anatomic repair of the joint when possible is the primary management option in traumatic knee injuries. The armamentarium of non-surgical treatments in such cases focuses on providing symptomatic relief and restoring joint mobility, critically leaving the need for arthritic management unmet [3]. Therapeutics that can successfully halt the destructive inflammatory activity in the knee immediately after injury represents an ideal non-surgical option to alter the course of osteoarthritis development
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