Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis

作者：Christiansen B A^*; Anderson M J; Lee C A; Williams J C; Yik J H N; Haudenschild D R

来源：Osteoarthritis and Cartilage, 2012, 20(7): 773-782.

DOI：10.1016/j.joca.2012.04.014

• Post-traumatic osteoarthritis
• Knee injury
• Subchondral bone
• Mouse model
• Articular cartilage

Objective: Post-traumatic osteoarthritis (PTOA) is a common consequence of traumatic joint injury, with 50% of anterior cruciate ligament (ACL) rupture patients developing PTOA within 10-20 years. Currently accepted mouse models of PTOA initiate symptoms using various methods, none of which faithfully mimic clinically-relevant injury conditions. In this study we characterize a novel non-invasive mouse model of PTOA that injures the ACL with a single load of tibial compression overload. We utilize this model to determine the time course of articular cartilage and subchondral bone changes following knee injury.
Design: Mice were euthanized 1, 3, 7, 14, 28, or 56 days after non-invasive knee injury. Knees were scanned using micro-computed tomography (mu CT) in order to quantify subchondral trabecular bone, subchondral bone plate, and non-native bone formation (heterotopic ossification). Development of osteoarthritis (OA) was graded using the osteoarthritis research society international (OARS!) scale on histological sections of injured and uninjured knees.
Results: Following injury we observed a rapid loss of trabecular bone in injured knees compared to uninjured knees by 7 days post-injury, followed by a partial recovery of trabecular bone to a new steady state by 28 days post-injury. We also observed considerable non-native bone formation by 56 days post-injury. Grading of histological sections revealed deterioration of articular cartilage by 56 days post-injury, consistent with development of mild OA.
Conclusions: This study establishes a novel mouse model of PTOA, and describes the time course of musculoskeletal changes following knee injury, helping to establish the window of opportunity for preventative treatment.

• 出版日期2012-7