Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability

Chang, Song Ho; Yasui, Toshihiro; Taketomi, Shuji; Matsumoto, Takumi; Kim‐Kaneyama, Joo‐ri; Omiya, Toshinobu; Hosaka, Yoko; Inui, Hiroshi; Omata, Yasunori; Yamagami, Ryota; Mori, Daisuke; Yano, Fumiko; Chung, Ung‐il; Tanaka, Sakae; Saito, Taku

doi:10.1016/j.joca.2015.11.008

Cited by 26 publications

(43 citation statements)

References 34 publications

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“…Recently, Change et al described an aging model, as well as three destabilization models of mouse ankle OA . First, ankle and knee cartilage from 25‐month‐old mice were compared to cartilage obtained from humans undergoing joint replacement surgery.…”

Section: Modeling Ankle Ptoa In Vivomentioning

confidence: 99%

“…The cartilage lesion should be located in an analogous location in ankle, and be of similar size, type and depth as clinically observed lesions, which is difficult or impossible to control in rodents. Recently, a mouse model of ankle OA was described based on surgical destabilization . Rabbit models are slightly larger and have been used in single impact studies of knee PTOA without the confounding variables of instability …”

Section: Considerations For Development Of New Preclinical Models Of mentioning

confidence: 99%

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Post‐traumatic osteoarthritis of the ankle: A distinct clinical entity requiring new research approaches

Delco

Kennedy

Bonassar

et al. 2016

Journal Orthopaedic Research

112

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The diagnosis of ankle osteoarthritis (OA) is increasing as a result of advancements in non-invasive imaging modalities such as magnetic resonance imaging, improved arthroscopic surgical technology and heightened awareness among clinicians. Unlike OA of the knee, primary or age-related ankle OA is rare, with the majority of ankle OA classified as post-traumatic (PTOA). Ankle trauma, more specifically ankle sprain, is the single most common athletic injury, and no effective therapies are available to prevent or slow progression of PTOA. Despite the high incidence of ankle trauma and OA, ankle-related OA research is sparse, with the majority of clinical and basic studies pertaining to the knee joint. Fundamental differences exist between joints including their structure and molecular composition, response to trauma, susceptibility to OA, clinical manifestations of disease, and response to treatment. Considerable evidence suggests that research findings from knee should not be extrapolated to the ankle, however few ankle-specific preclinical models of PTOA are currently available. The objective of this article is to review the current state of ankle OA investigation, highlighting important differences between the ankle and knee that may limit the extent to which research findings from knee models are applicable to the ankle joint. Considerations for the development of new ankle-specific, clinically relevant animal models are discussed.

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Section: Modeling Ankle Ptoa In Vivomentioning

confidence: 99%

Section: Considerations For Development Of New Preclinical Models Of mentioning

confidence: 99%

Post‐traumatic osteoarthritis of the ankle: A distinct clinical entity requiring new research approaches

Delco

Kennedy

Bonassar

et al. 2016

Journal Orthopaedic Research

112

View full text Add to dashboard Cite

show abstract

“…Population prevalence of OA varies by joint, with hand, knee, and hip affected in approximately 15%, 12%, and 6%, respectively, but the proportion attributed to trauma has a different pattern with ankle >> knee >> hip . The vast majority of mouse PTOA models focus on the knee, with only two recent studies in the ankle and none in the hip. Limited available data from genetically modified mice suggests the molecular pathophysiology of OA may differ between joints, so preclinical ankle and hip PTOA models represent a fertile area for future research.…”

Section: What Is Post‐traumatic Osteoarthritis (Ptoa)?mentioning

confidence: 99%

Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

Blaker

Clarke

Little

2016

Journal Orthopaedic Research

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Post-traumatic osteoarthritis (PTOA) is defined by its development after joint injury. Factors contributing to the risk of PTOA occurring, the rate of progression, and degree of associated disability in any individual, remain incompletely understood. What constitutes an "OA-inducing injury" is not defined. In line with advances in the traumatic brain injury field, we propose the scope of PTOA-inducing injuries be expanded to include not only those causing immediate structural damage and instability (Type I), but also those without initial instability/damage from moderate (Type II) or minor (Type III) loading severity. A review of the literature revealed this full spectrum of potential PTOA subtypes can be modeled in mice, with 27 Type I, 6 Type II, and 4 Type III models identified. Despite limitations due to cartilage anatomy, joint size, and bio-fluid availability, mice offer advantages as preclinical models to study PTOA, particularly genetically modified strains. Histopathology was the most common disease outcome, cartilage more frequently studied than bone or synovium, and meniscus and ligaments rarely evaluated. Other methods used to examine PTOA included gene expression, protein analysis, and imaging. Despite the major issues reported by patients being pain and biomechanical dysfunction, these were the least commonly measured outcomes in mouse models. Informative correlations of simultaneously measured disease outcomes in individual animals, was rarely done in any mouse PTOA model. This review has identified knowledge gaps that need to be addressed to increase understanding and improve prevention and management of PTOA. Preclinical mouse models play a critical role in these endeavors. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:424-439, 2017.

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“…Only age or surgically induced rat OA model is currently available [6]. The aging model has the obvious disadvantage of a longtime requirement and is associated with slight denaturation.…”

Section: Introductionmentioning

confidence: 99%

A Novel Rat Model of Ankle Osteoarthritis Induced by the Application of Monoiodoacetate

Jimbo¹,

Terashima²,

Takebayashi³

et al. 2017

J Arthritis

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Although ankle osteoarthritis is a common human joint disease, the etiological mechanisms underlying the associated pain remain unknown. We developed a new rat model of ankle osteoarthritis (OA) induced by monoiodoacetate (MIA) and evaluated the behavioral and histological characteristics of these animals. 60 male Sprague-Dawley rats were divided into three experimental groups of 20 rats. OA was induced by injecting the metabolic inhibitor MIA (1 mg/30 µl) into the tibiotarsal joint of the right hind paw on two consecutive days (MIA2 group) or single day (MIA1 group). Saline was injected into sham rats using the same protocol (sham group). We examined ankle swelling, range of motion, and stride length. We also assessed pain related behavior by observing the mechanical and thermal withdrawal responses. Rats were sacrificed 28 days after MIA/saline injection, and the right ankle joints were removed. Ankle sections were stained with safranin-O fast green, and histopathological changes were observed and scored. Both MIA groups exhibited significant increase in the ankle anteroposterior and transverse diameters (i.e., swelling) on days 7, 14, 21, and 28 post-injection relative to sham, as well as significantly decrease ROMs of the ankle. MIA2 rats additionally had a significantly shorter stride than did sham rats. MIA2 rats also exhibited an increased mechanical response frequency to the von Frey hair 4 g, and 6g tests, compared with sham rats, whereas MIA1 rats did not differ significantly from sham rats. Both MIA2 and MIA1 rats exhibited significantly reduced thermal latency in the hind paw relative to the sham group on day 28 post-injection. Histologically, the both MIA groups had a significantly higher score on day 28 post-injection, compared with the sham rats. MIA2 rats also exhibited more histological evidence of cartilage damage and abnormal medial tibia morphology, compared to MIA1 and sham rats.

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Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability

Abstract: Since human and mouse ankles are comparable, the present models will contribute to ankle OA pathophysiology and general cartilage research in future.

Cited by 26 publications

References 34 publications

Post‐traumatic osteoarthritis of the ankle: A distinct clinical entity requiring new research approaches

Post‐traumatic osteoarthritis of the ankle: A distinct clinical entity requiring new research approaches

Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

A Novel Rat Model of Ankle Osteoarthritis Induced by the Application of Monoiodoacetate

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