In vitro laxity-testers for knee joints of mice

Post-traumatic osteoarthritis (PTOA) is a common long-term consequence of joint injuries such as anterior cruciate ligament (ACL) rupture. In this study we used a tibial compression overload mouse model to compare knee injury induced at low speed (1 mm/s), which creates an avulsion fracture, to injury induced at high speed (500 mm/s), which induces midsubstance tear of the ACL. Mice were sacrificed at 0 days, 10 days, 12 weeks, or 16 weeks post-injury, and joints were analyzed with micro-computed tomography, whole joint histology, and biomechanical laxity testing. Knee injury with both injury modes caused considerable trabecular bone loss by 10 days post-injury, with the Low Speed Injury group (avulsion) exhibiting a greater amount of bone loss than the High Speed Injury group (midsubstance tear). Immediately after injury, both injury modes resulted in greater than 2-fold increases in total AP joint laxity relative to control knees. By 12 and 16 weeks post-injury, total AP laxity was restored to uninjured control values, possibly due to knee stabilization via osteophyte formation. This model presents an opportunity to explore fundamental questions regarding the role of bone turnover in PTOA, and the findings of this study support a biomechanical mechanism of osteophyte formation following injury.

Section: Discussioncontrasting

confidence: 57%

Section: Methodsmentioning

confidence: 99%

Comparison of loading rate‐dependent injury modes in a murine model of post‐traumatic osteoarthritis

Lockwood

Chu

Anderson

et al. 2013

“…The effect of this soft tissue injury on long‐term stability of the joint may prove relevant for ascertaining the healing and mechanical loading of the hip joint in vivo. For well‐established small animal models of knee OA, the quantitative assessment of anterior‐posterior and varus–valgus translation are commonly used as methods for assessing stability and laxity of the knee joint . However, at this time, no such established methods exist for assessing hip joint laxity or for the quantitative measure of hip joint stability for small animal models.…”

Section: Discussionmentioning

confidence: 99%

Novel model for the induction of postnatal murine hip deformity

Killian

Locke

James

et al. 2018

Acetabular dysplasia is a common, multi-etiological, pre-osteoarthritic (OA) feature that can lead to pain and instability of the young adult hip. Despite the clinical significance of acetabular dysplasia, there is a paucity of small animal models to investigate structural and functional changes that mediate morphology of the dysplastic hip and drive the subsequent OA cascade. Utilizing a novel murine model developed in our laboratory, this study investigated the role of surgically induced unilateral instability of the postnatal hip on the initiation and progression of acetabular dysplasia and impingement up to 8-weeks post-injury. C57BL6 mice were used to develop titrated levels of hip instability (i.e., mild, moderate, and severe instabillity or femoral head resection) at weaning. Joint shape, acetabular coverage, histomorphology, and statistical shape modeling were used to assess quality of the hip following 8 weeks of destabilization. Acetabular coverage was reduced following severe, but not moderate, instability. Moderate instability induced lateralization of the femur without dislocation, whereas severe instability led to complete dislocation and pseudoacetabulae formation. Mild instability did not result in morphological changes to the hip. Removal of the femoral head led to reduced hip joint space volume. These data support the notion that hip instability, driven by mechanical loss-of-function of soft connective tissue, can induce morphometric changes in the growing mouse hip. This work developed a new mouse model to study hip health in the murine adolescent hip and is a useful tool for investigating the mechanical and structural adaptations to hip instability during growth.

“…18 All joints were regularly moistened with phosphate-buffered saline (PBS) throughout specimen preparation and testing. Knees were positioned in 608 flexion 18,29 and preconditioned at a constant rate of 0.5 mm/s for five cycles by loading the tibia against a stationary femur to a displacement of AE0.25mm in the anteroposterior direction. Following preconditioning, samples were tested using a tibial displacement of AE0.50 mm for 10 cycles.…”

Section: Methodsmentioning

confidence: 99%

Variability in tendon and knee joint biomechanics among inbred mouse strains

Wang

Banack

Tsai

et al. 2006

Hereditary factors are thought to be responsible for impaired tendon function and joint laxity. The present study investigated the genotypic variability of knee laxity and stiffness and tendon mechanical and geometric properties among 16-week-old female A/J, C57BL/6J (B6), and C3H/HeJ (C3H) inbred mice. In one group of mice, knee mechanics were quantified using a custom loading apparatus enabling translation of the tibia against a stationary femur. In a second group, flexor digitorum longus and Achilles tendons from the left hind limb underwent biomechanical testing, while those of the contralateral limb were analyzed histologically for determination of crosssectional area. Our results demonstrate that tendon and joint mechanics varied significantly among the inbred mouse strains, indicating that biomechanical properties are genetically determined. A/J mouse knees exhibited greater laxity (p < 0.001) and lower stiffness (p < 0.001) compared to those of the B6 and C3H mice. The genotypic differences in whole joint properties were similar to those of the tendons' structural biomechanical traits. Although body mass did not differ (p > 0.2) among the three strains, significant genotypic differences were found at the whole tendon, material quality, and morphological levels of the tissue hierarchy. Furthermore, genetic regulation of tendon mechanical properties varied with anatomic site. Patterns of genotypic differences in tendon size were not consistent with those of biomechanical properties, suggesting that unique combinations of structural and compositional factors contribute to tendon growth, adaptation, and development. Therefore, the three inbred strains constitute a useful experimental model to elucidate genetic control of structure-function relationships in normal and healing tendons and ligaments.