Abstract
Objectives:
The primary aim of the present study is to evaluate the impact of timing of ACLR on the development of PTOA using a murine non-surgical (“closed”) ACL rupture model. The secondary aim is to evaluate the impact of the timing of ACLR on pain-related gait behaviors, peripheral and central immune and inflammatory response, knee range of motion (ROM), and tendon-bone healing.
Methods:
Fifty-five 11-12-week-old male B6 mice were randomized to one of three conditions: ACL rupture only, ACL rupture followed by immediate ACLR, or ACL rupture followed by delayed ACLR (7 days post-injury). There was also an uninjured control group included in the analysis. Mice in the immediate and delayed ACLR groups were sacrificed at 28 days postoperatively, and the ACL rupture group was sacrificed at 28 days post-injury. The primary outcome measure was histologic evaluation of osteoarthritis. The secondary outcomes included knee range of motion (ROM) testing, analysis of immune cells in ipsilateral iliac lymph node [iLN] and spleen using flow cytometry, gait analysis, and micro-computed tomography (µCT) analysis.
Results:
The ACL rupture and delayed ACLR groups had higher femoral OARSI scores (more OA) compared to the control (p < 0.0001 and p < 0.0001, respectively) and immediate ACLR groups (p < 0.001 and p < 0.0001, respectively), indicative of more severe osteoarthritis. In addition, the ACL rupture and delayed ACLR groups had higher tibial OARSI scores compared to the control (p < 0.0001 and p < 0.001, respectively) and immediate ACLR groups (p < 0.01 and p < 0.01, respectively, Figures 1, 2). There were no differences between groups with respect to range of motion (Figure 3), tendon-bone healing at the femoral or tibial tunnels on µCT or pain-related gait behaviors (Figure 4). There was an increase in total ipsilateral iliac lymph node cellularity in the surgical cohorts compared to the ACL rupture and control cohorts.
Conclusions:
We found that immediate ACLR mitigates the development of PTOA in a murine closed anterior cruciate ligament rupture model. Future studies aimed at elucidating the role of ACLR timing and inflammation on the development of PTOA will allow us to better address this very common and detrimental sequelae of ACL injuries.
