Survey of Animal Models in Post-Traumatic Arthritis: Choosing the Right Model to Answer the Right Question

Furman, Bridgette D.; Kimmerling, Kelly A.; Wu, Chia‐Lung; Little, Dianne; Guilak, Farshid; Olson, Steven A.

doi:10.1007/978-1-4899-7606-2_10

Cited by 2 publications

(4 citation statements)

References 35 publications

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“…Although mice are the most used, rats, guinea pigs, rabbits, cats, dogs, sheep, goats, mini pigs and pigs are also suitable. 71 72 Experimental PTA is generally induced either through a surgical intervention, or by causing a physical trauma directly in the joint. In the first case, the knee patellar ligament is transected and the medial lateral menisci removed with a microsurgical technique.…”

Section: In Vitro and In Vivo Modelsmentioning

confidence: 99%

“…Despite the significant progress in the development of mouse PTA models, a consensus about the best procedure to use in translational studies is still lacking. 72 Nonetheless, the animal models remain, at least for the moment, irreplaceable to reproduce the biological processes involved in PTA onset and for the development of new therapies.…”

Section: In Vitro and In Vivo Modelsmentioning

confidence: 99%

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Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation

et al. 2016

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Post-traumatic arthritis (PTA) develops after an acute direct trauma to the joints. PTA causes about 12% of all osteoarthritis cases, and a history of physical trauma may also be found in patients with chronic inflammatory arthritis. Symptoms include swelling, synovial effusion, pain and sometimes intra-articular bleeding. Usually, PTA recoveries spontaneously, but the persistence of symptoms after 6 months may be considered pathological and so-called chronic PTA. A variety of molecular, mechanobiological and cellular events involved in the pathogenesis and the progression of PTA have been identified. The activation of inflammatory mechanisms during the PTA acute phase appears to play a critical role in the chronic disease onset. Human studies and experimental models have revealed that a series of inflammatory mediators are released in synovial fluid immediately after the joint trauma. These molecules have been proposed as markers of disease and as a potential target for the development of specific and preventative interventions. Currently, chronic PTA cannot be prevented, although a large number of agents have been tested in preclinical studies. Given the relevance of inflammatory reaction, anticytokines therapy, in particular the inhibition of interleukin 1 (IL-1), seems to be the most promising strategy. At the present time, intra-articular injection of IL-1 receptor antagonist is the only anticytokine approach that has been used in a human study of PTA. Despite the fact that knowledge in this area has increased in the past years, the identification of more specific disease markers and new therapeutic opportunities are needed.

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Section: In Vitro and In Vivo Modelsmentioning

confidence: 99%

Section: In Vitro and In Vivo Modelsmentioning

confidence: 99%

Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation

et al. 2016

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“…Furthermore, study design and outcomes will vary greatly for research questions along the spectrum of translation to the clinic; for example, studies may ask—“Is the patient satisfied?” or “Is biomechanical function achieved?,” seek to understand fundamental tendon and ligament biologic mechanisms or answer unbiased discovery questions using sequencing platforms. The short answer to many of the questions regarding selection of preclinical tendon and ligament models, as in other areas of orthopedics, 1 is “It depends.” A perfect model does not exist and seeking to develop such a model, or to prescribe use of a specific model may hinder progress. Answering these broad questions, however, was useful for delineating the core set of considerations for choosing the most appropriate preclinical tendon or ligament model for a particular study, and for defining the most important questions for pushing the field forward and driving innovation.…”

Section: Introductionmentioning

confidence: 99%

“…or "Is biomechanical function achieved?," seek to understand fundamental tendon and ligament biologic mechanisms or answer unbiased discovery questions using sequencing platforms. The short answer to many of the questions regarding selection of preclinical tendon and ligament models, as in other areas of orthopedics, 1 is "It depends." A perfect model does not exist and seeking to develop such a model, or to prescribe use of a specific model may hinder progress.…”

Section: Introductionmentioning

confidence: 99%

Preclinical tendon and ligament models: Beyond the 3Rs (replacement, reduction, and refinement) to 5W1H (why, who, what, where, when, how)

Little

Amadio

Awad

et al. 2023

Journal Orthopaedic Research

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Several tendon and ligament animal models were presented at the 2022 Orthopaedic Research Society Tendon Section Conference held at the University of Pennsylvania, May 5‐7, 2022. A key objective of the breakout sessions at this meeting was to develop guidelines for the field, including for preclinical tendon and ligament animal models. This review summarizes the perspectives of experts for eight surgical small and large animal models of rotator cuff tear, flexor tendon transection, anterior cruciate ligament tear, and Achilles tendon injury using the framework: “Why, Who, What, Where, When, and How” (5W1H). A notable conclusion is that the perfect tendon model does not exist; there is no single gold standard animal model that represents the totality of tendon and ligament disease. Each model has advantages and disadvantages and should be carefully considered in light of the specific research question. There are also circumstances when an animal model is not the best approach. The wide variety of tendon and ligament pathologies necessitates choices between small and large animal models, different anatomic sites, and a range of factors associated with each model during the planning phase. Attendees agreed on some guiding principles including: providing clear justification for the model selected, providing animal model details at publication, encouraging sharing of protocols and expertise, improving training of research personnel, and considering greater collaboration with veterinarians. A clear path for translating from animal models to clinical practice was also considered as a critical next step for accelerating progress in the tendon and ligament field.This article is protected by copyright. All rights reserved.

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Survey of Animal Models in Post-Traumatic Arthritis: Choosing the Right Model to Answer the Right Question

Cited by 2 publications

References 35 publications

Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation

Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation

Preclinical tendon and ligament models: Beyond the 3Rs (replacement, reduction, and refinement) to 5W1H (why, who, what, where, when, how)

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