Development of an in vitro model of injury-induced osteoarthritis in cartilage explants from adult horses through application of single-impact compressive overload.
Abstract: To develop an in vitro model of cartilage injury in full-thickness equine cartilage specimens that can be used to simulate in vivo disease and evaluate treatment efficacy. Methods: 15 full-thickness cartilage explants from the trochlear ridges of the distal aspect of the femur from each of 6 adult horses that had died from reasons unrelated to the musculoskeletal system. Methods: To simulate injury, cartilage explants were subjected to single-impact uniaxial compression to 50%, 60%, 70%, or 80% strain at a rate of 100% strain/s. Other explants were left uninjured (control specimens). All specimens underwent a culture process for 28 days and were subsequently evaluated histologically for characteristics of injury and early stages of osteoarthritis, including articular surface damage, chondrocyte cell death, focal cell loss, chondrocyte cluster formation, and loss of the extracellular matrix molecules aggrecan and types I and II collagen. Results: Compression to all degrees of strain induced some amount of pathological change typical of clinical osteoarthritis in horses; however, only compression to 60% strain induced significant changes morphologically and biochemically in the extracellular matrix. Conclusions: The threshold strain necessary to model injury in full-thickness cartilage specimens from the trochlear ridges of the distal femur of adult horses was 60% strain at a rate of 100% strain/s. This in vitro model should facilitate study of pathophysiologic changes and therapeutic interventions for osteoarthritis.
Publication Date: 2012-12-29 PubMed ID: 23270344DOI: 10.2460/ajvr.74.1.40Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research examines an in-vitro model developed for studying the impacts of injury-induced osteoarthritis on horse cartilage. The study establishes that a strain of 60% at a rate of 100% strain/second is needed for mimicking the damage in full-thickness horse cartilage, providing a way to investigate the disease’s changes and potential treatments.
Methodology
- The scientists obtained full-thickness cartilage explants from the trochlear ridges of the distal femur of six adult horses that have died due to reasons not related to the musculoskeletal system.
- To simulate injuries that could cause osteoarthritis, these explant samples were compressed uniaxially to 50%, 60%, 70%, or 80% strain at a 100% strain/second rate. There were also control specimens that remained uninjured.
- Post this, all specimens were cultured for 28 days before undergoing histological evaluation for early signs and features of osteoarthritis, such as surface damage to articular, chondrocyte cell death, chondrocyte cluster formation, localized cell loss, and the diminishing of the molecules aggrecan and types I and II collagen.
Results
- Compression to all levels of strain triggered some pathological changes reminiscent of clinical osteoarthritis in horses.
- However, only compression to a 60% strain led to significant alterations at both molecular and morphological levels in the extracellular matrix, a three-dimensional network of extracellular macromolecules such as collagen, enzymes, and glycoproteins that provide structural and biochemical support to cells.
Conclusion
- The researchers concluded that to simulate injury in full-thickness cartilage specimens from adult horses, a stress of 60% at a 100% strain/second rate was imperative.
- This in-vitro model could potentially become a robust tool for studying pathophysiologic changes and therapeutic interventions for osteoarthritis, thereby potentially aiding in improving treatments for humans suffering from osteoarthritis.
Cite This Article
APA
Lee CM, Kisiday JD, McIlwraith CW, Grodzinsky AJ, Frisbie DD.
(2012).
Development of an in vitro model of injury-induced osteoarthritis in cartilage explants from adult horses through application of single-impact compressive overload.
Am J Vet Res, 74(1), 40-47.
https://doi.org/10.2460/ajvr.74.1.40 Publication
Researcher Affiliations
- Orthopaedic Research Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.
MeSH Terms
- Aggrecans / metabolism
- Animals
- Cartilage, Articular / injuries
- Cartilage, Articular / metabolism
- Cartilage, Articular / pathology
- Cell Death
- Chondrocytes / metabolism
- Chondrocytes / pathology
- Collagen Type I / metabolism
- Collagen Type II / metabolism
- Disease Models, Animal
- Extracellular Matrix / metabolism
- Extracellular Matrix / pathology
- Horses
- In Vitro Techniques
- Osteoarthritis / etiology
- Osteoarthritis / pathology
- Stifle / injuries
- Stifle / metabolism
- Stifle / pathology
Citations
This article has been cited 8 times.- Kurz B, Hart ML, Rolauffs B. Mechanical Articular Cartilage Injury Models and Their Relevance in Advancing Therapeutic Strategies.. Adv Exp Med Biol 2023;1402:107-124.
- Kim B, Bonassar LJ. Understanding the Influence of Local Physical Stimuli on Chondrocyte Behavior.. Adv Exp Med Biol 2023;1402:31-44.
- Samvelyan HJ, Hughes D, Stevens C, Staines KA. Models of Osteoarthritis: Relevance and New Insights.. Calcif Tissue Int 2021 Sep;109(3):243-256.
- Haltmayer E, Ribitsch I, Gabner S, Rosser J, Gueltekin S, Peham J, Giese U, Dolezal M, Egerbacher M, Jenner F. Co-culture of osteochondral explants and synovial membrane as in vitro model for osteoarthritis.. PLoS One 2019;14(4):e0214709.
- Nickien M, Heuijerjans A, Ito K, van Donkelaar CC. Comparison between in vitro and in vivo cartilage overloading studies based on a systematic literature review.. J Orthop Res 2018 Apr 12;36(8):2076-86.
- Henak CR, Bartell LR, Cohen I, Bonassar LJ. Multiscale Strain as a Predictor of Impact-Induced Fissuring in Articular Cartilage.. J Biomech Eng 2017 Mar 1;139(3):0310041-8.
- McCulloch RS, Ashwell MS, Maltecca C, O'Nan AT, Mente PL. Progression of Gene Expression Changes following a Mechanical Injury to Articular Cartilage as a Model of Early Stage Osteoarthritis.. Arthritis 2014;2014:371426.
- Lee CM, Kisiday JD, McIlwraith CW, Grodzinsky AJ, Frisbie DD. Synoviocytes protect cartilage from the effects of injury in vitro.. BMC Musculoskelet Disord 2013 Feb 1;14:54.
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