A Mouse Noninvasive Intraarticular Tibial Plateau Compression Loading-Induced Injury Model of Posttraumatic Osteoarthritis
Autor: | Virginia Stiffel, Matilda H.-C. Sheng, Kin-Hing William Lau, Charles H. Rundle, Subhashri Das |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
musculoskeletal diseases Cartilage Articular Male medicine.medical_specialty Arthritic changes Compressive Strength Knee Joint Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Osteoarthritis Knee Injuries Meniscus (anatomy) Plateau (mathematics) Article Weight-Bearing 03 medical and health sciences Mice 0302 clinical medicine Endocrinology medicine Animals Orthopedics and Sports Medicine Orthodontics Tibia business.industry medicine.disease Compression (physics) musculoskeletal system Mice Inbred C57BL Tibial Fractures Disease Models Animal medicine.anatomical_structure Orthopedic surgery Ligament Female 030101 anatomy & morphology Injury model Stress Mechanical business Leg Injuries |
Zdroj: | Calcif Tissue Int |
Popis: | This study sought to develop a noninvasive, reliable, clinically relevant, and easy-to-implement mouse model that can be used for investigation of the pathophysiology of PTOA and for preclinical testing of new therapies of PTOA. Accordingly, we have established a closed intraarticular tibial plateau compression loading-induced injury model of PTOA in C57BL/6J mice. In this model, a single application of a defined loading force was applied with an indenter to the tibial plateau of the right knee to create injuries to the synovium, menisci, ligaments, and articular cartilage. The limiting loading force was set at 55 N with the loading speed of 60 N/s. This loading regimen limits the distance that the indenter would travel into the joint, but still yields substantial compression loading energy to cause significant injuries to the synovium, meniscus, and articular cartilage. The joint injury induced by this loading protocol consistently yielded evidence for key histological hallmarks of PTOA at 5–11 weeks post-injury, including loss of articular cartilage, disorganization of chondrocytes, meniscal hyperplasia and mineralization, osteophyte formation, and degenerative remodeling of subchondral bone. These arthritic changes were highly reproducible and of a progressive nature. Because 50% of patients with meniscal and/or ligament injuries without intraarticular fractures developed PTOA over time, this intraarticular tibial plateau compression loading-induced injury model is clinically relevant. In summary, we have developed a noninvasive intraarticular tibial plateau compression loading-induced injury model in the mouse that can be used to investigate the pathophysiology of PTOA and for preclinical testing for new therapies. |
Databáze: | OpenAIRE |
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