Patients with osteoarthritis (OA) primarily seek treatment due to pain and disability, yet the primary endpoints for rodent OA models tend to be histological measures of joint destruction. The discrepancy between clinical and preclinical evaluations is problematic, given that radiographic evidence of OA in humans does not always correlate to the severity of patient-reported symptoms. Recent advances in behavioral analyses have provided new methods to evaluate disease sequelae in rodents. Of particular relevance to rodent OA models are methods to assess rodent gait. While obvious differences exist between quadrupedal and bipedal gait sequences, the gait abnormalities seen in humans and in rodent OA models reflect similar compensatory behaviors that protect an injured limb from loading. The purpose of this review is to describe these compensations and current methods used to assess rodent gait characteristics, while detailing important considerations for the selection of gait analysis methods in rodent OA models.

IntroductionAfter transection of the medial collateral ligament and medial meniscus (MCLT + MMT) in the rat, focal cartilage lesions develop over 4–6 weeks; however, sham surgery (MCLT alone) does not result in cartilage damage over a similar period. Thus, comparison of MCLT + MMT with the MCLT sham group offers an opportunity to investigate behavioral modifications related to focal cartilage and meniscus damage in the rat.MethodsMCLT or MCLT + MMT surgery was performed in the right knees of male Lewis rats, with spatiotemporal gait patterns and hind limb sensitivity assessed at 1, 2, 4, and 6 weeks postsurgery (n = 8 rats per group per time point, n = 64 total). After the animals were euthanized, Histology was performed to assess joint damage.ResultsMCLT + MMT animals had unilateral gait compensations at early time points, but by week 6 bilateral gait compensations had developed in both the MCLT sham and MCLT + MMT groups. Conversely, heightened tactile sensitivity was detected in both MCLT sham and MCLT + MMT animals at week 1, but only the MCLT + MMT animals maintained heightened sensitivity to week 6. Cartilage lesions were found in the MCLT + MMT group but not in the MCLT sham group. Correlations could be identified between joint damage and gait changes in MCLT + MMT animals; however, the same gait changes were found with MCLT sham animals despite a lack of joint damage.ConclusionsCombined, our data highlight a common conundrum in osteoarthritis (OA) research: Some behavioral changes correlate to cartilage damage in the OA group, but the same changes can be identified in non-OA controls. Of the behavioral changes detected, allodynia was maintained in MCLT + MMT animals but not in the MCLT sham group. However, the correlation between cartilage damage and hind limb sensitivity is relatively weak (R = −0.4498), and the range of sensitivity measures overlaps between groups. The factors driving gait abnormalities in MCLT and MCLT + MMT animals also remain uncertain. The gait modifications are similar between groups and do not appear until weeks after surgery, despite cartilage damage being focused in the MCLT + MMT group. Combined, our data highlight the need to evaluate the links between noncartilage changes and behavioral changes following joint injury in the rat.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0791-2) contains supplementary material, which is available to authorized users.

Biodegradable magnesium (Mg) alloys combine the advantages of traditional metallic implants and biodegradable polymers, having high strength, low density, and a stiffness ideal for bone fracture fixation. A recently developed Mg-Ca-Sr alloy potentially possesses advantageous characteristics over other Mg alloys, such as slower degradation rates and minimal toxicity. In this study, the biocompatibility of this Mg-Ca-Sr alloy was investigated in a rat pin-placement model. Cylindrical pins were inserted in the proximal tibial metaphyses in pre-drilled holes orthogonal to the tibial axis. Implant and bone morphologies were investigated using μCT at 1, 3, and 6 weeks after implant placement. At the same time points, the surrounding tissue was evaluated using H&E, TRAP and Goldner's trichrome staining. Although gas bubbles were observed around the degrading implant at early time points, the bone remained intact with no evidence of microfracture. Principle findings also include new bone formation in the area of the implant, suggesting that the alloy is a promising candidate for biodegradable orthopedic implants.

Locomotive changes are often associated with disease or injury, and these changes can be quantified through gait analysis. Gait analysis has been applied to preclinical studies, providing quantitative behavioural assessment with a reasonable clinical analogue. However, available gait analysis technology for small animals is somewhat limited. Furthermore, technological and analytical challenges can limit the effectiveness of preclinical gait analysis. The Gait Analysis Instrumentation and Technology Optimized for Rodents (GAITOR) Suite is designed to increase the accessibility of preclinical gait analysis to researchers, facilitating hardware and software customization for broad applications. Here, the GAITOR Suite’s utility is demonstrated in 4 models: a monoiodoacetate (MIA) injection model of joint pain, a sciatic nerve injury model, an elbow joint contracture model, and a spinal cord injury model. The GAITOR Suite identified unique compensatory gait patterns in each model, demonstrating the software’s utility for detecting gait changes in rodent models of highly disparate injuries and diseases. Robust gait analysis may improve preclinical model selection, disease sequelae assessment, and evaluation of potential therapeutics. Our group has provided the GAITOR Suite as an open resource to the research community at www.GAITOR.org, aiming to promote and improve the implementation of gait analysis in preclinical rodent models.

Objective In rodent osteoarthritis models, behavioral changes are often subtle and require highly sensitive methods to detect these changes. Gait analysis is one assay that may provide sensitive, quantitative measurement of these behavioral changes1. To increase detection sensitivity of gait assessments relative to spatiotemporal gait collection alone, we combined our spatiotemporal and dynamic gait collection systems. Using this combined system, gait was assessed in the rat medial meniscus transection model and monoiodoacetate injection model of knee osteoarthritis. Design 36 male Lewis rats were separated into medial meniscus transection (n=8), medial collateral ligament transection (n=8), skin incision (n=4), monoiodoacetate injection (n=8), and saline injection (n=8) groups. After initiation of osteoarthritis, gait data were collected weekly in each group out to 4 weeks. Results The medial meniscus transection and monoiodoacetate injection models produced unique pathologic gait profiles, with medial meniscus transection animals developing a shuffling gait and monoiodoacetate injection animals exhibiting antalgic gait. Spatiotemporal changes were also observed in the medial meniscus transection model at week 1 (p<0.01), but were not observed in the monoiodoacetate injection model until week 3 (p<0.01). Dynamic gait changes were observed in both models as early as 1 week post-surgery (p<0.01). Conclusion Combined analysis of spatiotemporal and dynamic gait data increased detection sensitivity for gait modification in two rat osteoarthritis models. Analyzing the combined gait data provided a robust characterization of the pathologic gait produced by each model. Furthermore, this characterization revealed different patterns of gait compensations in two common rat models of knee osteoarthritis.