non-invasive-compression-induced-anterior-cruciate-ligament-acl

Non-Invasive Compression-Induced Anterior Cruciate Ligament (ACL) Injury and <em>In Vivo</em> Imaging of Protease Activity in Mice

Traumatic joint injuries such as anterior cruciate ligament (ACL) rupture or meniscus tears commonly lead to post-traumatic osteoarthritis (PTOA) within ...

University of California Davis Health

We previously showed that femur fracture in mice caused a reduction in bone volume at distant skeletal sites within 2 weeks post-fracture. Osteocytes also have the ability to remodel their surrounding bone matrix through perilacunar/canalicular remodeling (PLR). If PLR is altered systemically following fracture, this could affect bone mechanical properties and increase fracture risk at all skeletal sites. In this study, we investigated whether lacunar-canalicular microstructure and the rate of PLR are altered in the contralateral limb following femoral fracture in mice. We hypothesized that femoral fracture would accelerate PLR by 2 weeks postfracture, followed by partial recovery by 4 weeks. We used histological evaluation and high-resolution microcomputed tomography to quantify the morphology of the lacunar-canalicular network at the contralateral tibia, and we used quantitative real-time polymerase chain reaction (RT-PCR) and RNA-seq to measure the expression of PLR-associated genes in the contralateral femur. We found that at both 2 and 4 weeks postfracture, canalicular width was significantly increased by 18.6% and 16.6%, respectively, in fractured mice relative to unfractured controls. At 3 days and 4 weeks post-fracture, we observed downregulation of PLR-associated genes; RNA-seq analysis at 3 days post-fracture showed a deceleration of bone formation and mineralization in the contralateral limb. These data demonstrate notable canalicular changes following fracture that could affect bone mechanical properties. These findings expand our understanding of systemic effects of fracture and how biological and structural changes at distant skeletal sites may contribute to increased fracture risk following an acute injury.

Altered canalicular remodeling associated with femur fracture in mice.

Noninvasive compression-induced anterior cruciate ligament rupture (ACL-R) is an easy and reproducible model for studying post-traumatic osteoarthritis (PTOA) in mice. However, equipment typically used for ACL-R is expensive, immobile, and not available to all researchers. In this study, we compared PTOA progression in mice injured with a low-cost custom ACL-rupture device (CARD) to mice injured with a standard system (ElectroForce 3200). We quantified anterior-posterior (AP) joint laxity immediately following injury, epiphyseal trabecular bone microstructure, and osteophyte volume at 2 and 6 weeks post injury using micro-computed tomography, and osteoarthritis progression and synovitis at 2 and 6 weeks post injury using whole-joint histology. We observed no significant differences in outcomes in mice injured with the CARD system compared to mice injured with the Electroforce (ELF) system. However, AP joint laxity data and week 2 micro-CT and histology outcomes suggested that injuries may have been slightly more severe and PTOA progressed slightly faster in mice injured with the CARD system compared to the ELF system. Altogether, these data confirm that ACL-R can be successfully and reproducibly performed with the CARD system and that osteoarthritis (OA) progression is mostly comparable to that of mice injured with the ELF system, though potentially slightly faster. The CARD system is low cost and portable, and we are making the plans and instructions freely available to all interested investigators in the hopes that they will find this system useful for their studies of OA in mice.

Yu-Yang Lin

Lawrence J. Ellison Musculoskeletal Research Center,
Department of Orthopaedic Surgery,
Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery

University of California Davis Health

Non-Invasive Compression-Induced Anterior Cruciate Ligament (ACL) Injury and In Vivo Imaging of Protease Activity in Mice

Yu-Yang Lin

Lawrence J. Ellison Musculoskeletal Research Center,Department of Orthopaedic Surgery,Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery

University of California Davis Health

Non-Invasive Compression-Induced Anterior Cruciate Ligament (ACL) Injury and In Vivo Imaging of Protease Activity in Mice

Lawrence J. Ellison Musculoskeletal Research Center,
Department of Orthopaedic Surgery,
Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery