Accelerated post traumatic osteoarthritis in a dual injury murine model

Abstract

Objective: Joint injury involving destabilisation of the joint and damage to the articular cartilage (e.g., sports-related injury) can result in accelerated post-traumatic osteoarthritis (PTOA). Destabilised medial meniscotibial ligament (DMM) surgery is one of the most commonly used murine models and whilst it recapitulates Osteoarthritis (OA) pathology, it does not necessarily result in multi-tissue injury, as occurs in PTOA. We hypothesised that simultaneous cartilage damage and joint destabilisation would accelerate the onset of OA pathology. Methods: OA was induced in C57BL/6 mice via (a) DMM, (b) microblade scratches of articular cartilage (CS) or (c) combined DMM and cartilage scratch (DCS). Mice were culled 7, 14 and 28 days post-surgery. Microcomputed tomography (mCT) and histology were used to monitor bone changes and inflammation. Dynamic weight bearing, an indirect measure of pain, was assessed on day 14. Results: Osteophytogenesis analysis via mCT revealed that osteophytes were present in all groups at days 7 and 14 post-surgery. However, in DCS, osteophytes were visually larger and more numerous when compared with DMM and cartilage scratch (CS). Histological assessment of cartilage at day 14 and 28, revealed significantly greater damage in DCS compared with DMM and CS. Furthermore, a significant increase in synovitis was observed in DCS. Finally, at day 14 osteophyte numbers correlated with changes in dynamic weight bearing. Conclusion: Joint destabilisation when combined with simultaneous cartilage injury accelerates joint deterioration, as seen in PTOA. Thus, DCS provides a novel and robust model for investigating multiple pathological hallmarks, including osteophytogenesis, cartilage damage, synovitis and OA-related pain.

Obesity and load‐induced posttraumatic osteoarthritis in the absence of fracture or surgical trauma

“…Using an intra-articular fracture model, obesity increased synovial inflammation. 10 Although synovitis and inflammation can occur in association with an initial DMM surgery, DMM can have differential effects on joint inflammation, as demonstrated by two reports, one showing low-level synovitis following DMM 33 while another did not find differences in synovitis. 34 Obesity increases synovial thickness and synovial inflammation in DMM.…”

Osteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation

“…First, it was previously shown that the development of histologic OA following DMM in mice is associated with poor functional outcomes including pain 58 , 59 . The data presented in this study demonstrate that the collagen–OSCAR interaction contributes to cartilage and joint degeneration following DMM, and consistent with prior works 58 , 59 . Such pathologic changes are expected to result in pain and impaired motile function.…”

Differential patterns of pathology in and interaction between joint tissues in long-term osteoarthritis with different initiating causes: phenotype matters

“…While histopathology rather than imaging remains the gold standard for measuring OA structural disease onset and progression in pre-clinical animal models, as in patients emphasis has shifted to a more global evaluation of joint-wide pathology facilitated in part by use of smaller species such as mice 19,21,22 . To date however, there has been limited investigation in pre-clinical models of the joint-tissue pathology associations observed in patients 23,24 , and none that we are aware of…”