Characterization of Non-Invasively Induced Post-Traumatic Osteoarthritis in Mice

Abstract

The pathophysiology of post-traumatic arthritis (PTOA) is not fully understood. This study used non-invasive repetitive mechanical loading (ML) mouse models to study biochemical, biomechanical, and pain-related behavioral changes induced in mice. Mouse models reflected the effects of the early stages of PTOA in humans. For the PTOA model, cyclic comprehensive loading (9N) was applied to each mouse’s left knee joint. ML-induced biochemical and molecular changes were analyzed after loading completion. Cartilage samples were examined using gene expression analysis. Tissue sections were used in subsequent OA severity scoring. Biomechanical features and pain-related behavior were studied after 24 h and three weeks post-ML sessions to examine the development of PTOA. The loaded left knee joint showed a greater ROS/RNS signal than the right knee, which was not loaded. There was a significant increase in cartilage damage and MMP activity in the mechanically loaded joints relative to non-loaded control knee joints. Similarly, we found a difference in the viscoelastic tangent, which highlights significant changes in mechanical properties. Biochemical analyses revealed significant increases in total NO, caspase-3 activity, H2O2, and PGE2 levels. Gene expression analysis highlighted increased catabolism (MMP-13, IL-1β, TNF-α) with a concomitant decrease in anabolism (ACAN, COL2A1). Histopathology scores clearly indicated increases in OA progression and synovitis. The gait pattern was significantly altered, suggesting signs of joint damage. This study showed that biomechanical, biochemical, and behavioral characteristics of the murine PTOA groups are significantly different from the control group. These results confirm that the current mouse model can be considered for translational PTOA studies.

Betulinic Acid Attenuates Osteoarthritis via Limiting NLRP3 Inflammasome Activation to Decrease Interleukin-1β Maturation and Secretion

“…A paper was used to record the footprints on the walkway. Finally, the base of support (BOS) hindpaws, the right hindpaws stride length, and the right–left hindpaws distance were quantified and analyzed and shown in Figures 2(a) and 2(b) [ 25 ].…”

Mechanical loading and orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA): a comprehensive review

“…Specifically, PTOA stems from injury to the AC, injury to the subchondral bone, misalignment of the joint surface, or joint instability resulting from sudden trauma such as joint fracture or ligament injury ( Kramer et al, 2011 ). A non-invasive mouse model of compressive joint loading demonstrated key features mimicking human PTOA including cartilage degeneration, synovitis, and subchondral bone changes ( Bhatti et al, 2022 ). All of these findings correlated with development of pian in humans at risk for PTOA ( Khella et al, 2021 ; Croen et al, 2023 ).…”

One session of 20 ​N cyclic compression induces chronic knee osteoarthritis in rats: A long-term study

“…Mechanical stimuli, have also been applied, in the form of repetitive cyclic compression events, causing ACL ruptures and tibial fatigue fractures. Increased cortical bone thickness and gait changes have been reported as characteristic changes induced by this type of mechanical stimuli [ 3 , [8] , [9] , [10] ]. Compared with mice models, few non-surgical rat models have been reported, although they are more advantageous for imaging modalities and therapeutic interventions [ 2 ].…”