Development of an in vitro model of injury-induced osteoarthritis in cartilage explants from adult horses through application of single-impact compressive overload

Lee, Christina M.; Kisiday, John D.; McIlwraith, C. Wayne; Grodzinsky, Alan J.; Frisbie, David D.

doi:10.2460/ajvr.74.1.40

Cited by 13 publications

(8 citation statements)

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“…Cartilage plugs were injured as previously defined [23]. In brief, cartilage plugs were removed from media and placed into a sterile polysulphone loading chamber consisting of a well aligned coaxially with an impermeable platen (10 mm diameter) in the absence of media.…”

Section: Methodsmentioning

confidence: 99%

“…The time points to evaluate gene expression were determined based on previous studies that have evaluated changes in gene expression in cartilage after injury [18,20]. For histologic evaluation we extended the duration of culture because in previous studies [23] we found injured cartilage required culture for at least 28 days to develop histologic changes. Each experiment was conducted in duplicate, and all experiments repeated a total of 6 times using cartilage from a new horse for each experiment and synoviocytes from 6 different horses total; synoviocytes from each horse were used for one gene expression and one histology experiment.…”

Section: Methodsmentioning

confidence: 99%

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Synoviocytes protect cartilage from the effects of injury in vitro

Lee

Kisiday

McIlwraith

et al. 2013

BMC Musculoskelet Disord

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BackgroundIt is well documented that osteoarthritis (OA) can develop following traumatic joint injury and is the leading cause of lameness and subsequent wastage of equine athletes. Although much research of injury induced OA has focused on cartilage, OA is a disease that affects the whole joint organ.MethodsIn this study, we investigated the impact of synovial cells on the progression of an OA phenotype in injured articular cartilage. Injured and control cartilage were cultured in the presence of synoviocytes extracted from normal equine synovium. Synoviocytes and cartilage were evaluated for catabolic and anabolic gene expression. The cartilage was also evaluated histologically for loss of extracellular matrix molecules, chondrocyte cell death and chondrocyte cluster formation.ResultsThe results indicate synoviocytes exert both positive and negative effects on injured cartilage, but ultimately protect injured cartilage from progressing toward an OA phenotype. Synoviocytes cultured in the presence of injured cartilage had significantly reduced expression of aggrecanase 1 and 2 (ADAMTS4 and 5), but also had increased expression of matrix metalloproteinase (MMP) -1 and reduced expression of tissue inhibitor of metalloproteinases 1 (TIMP-1). Injured cartilage cultured with synoviocytes had increased expression of both collagen type 2 and aggrecanase 2. Histologic examination of cartilage indicated that there was a protective effect of synoviocytes on injured cartilage by reducing the incidence of both focal cell loss and chondrocyte cluster formation, two major hallmarks of OA.ConclusionsThese results support the importance of evaluating more than one synovial joint tissue when investigating injury induced OA.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Synoviocytes protect cartilage from the effects of injury in vitro

Lee

Kisiday

McIlwraith

et al. 2013

BMC Musculoskelet Disord

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“…Due to technical challenges, most previous research has focused on bulk mechanics, wherein values are averaged over the entire 1-3 mm cartilage thickness (e.g., Refs. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]). Results from such measurements, however, often propose inexact thresholds based on limited groups of mechanical parameters, preventing the extraction of specific thresholds (e.g., Refs.…”

Section: Introductionmentioning

confidence: 99%

Multiscale Strain as a Predictor of Impact-Induced Fissuring in Articular Cartilage

Henak

Bartell

Cohen

et al. 2017

Journal of Biomechanical Engineering

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Mechanical damage is central to both initiation and progression of osteoarthritis (OA). However, specific causal links between mechanics and cartilage damage are incompletely understood, which results in an inability to predict failure. The lack of understanding is primarily due to the difficulty in simultaneously resolving the high rates and small length scales relevant to the problem and in correlating such measurements to the resulting fissures. This study leveraged microscopy and high-speed imaging to resolve mechanics on the previously unexamined time and length scales of interest in cartilage damage, and used those mechanics to develop predictive models. The specific objectives of this study were to: first, quantify bulk and local mechanics during impact-induced fissuring; second, develop predictive models of fissuring based on bulk mechanics and local strain; and third, evaluate the accuracy of these models in predicting fissures. To achieve these three objectives, bovine tibial cartilage was impacted using a custom spring-loaded device mounted on an inverted microscope. The occurrence of fissures was modulated by varying impact energy. For the first objective, during impact, deformation was captured at 10,000 frames per second and bulk and local mechanics were analyzed. For the second objective, data from samples impacted with a 1.2 mm diameter rod were fit to logistic regression functions, creating models of fissure probability based on bulk and local mechanics. Finally, for the third objective, data from samples impacted with a 0.8 mm diameter rod were used to test the accuracy of model predictions. This study provides a direct comparison between bulk and local mechanical thresholds for the prediction of fissures in cartilage samples, and demonstrates that local mechanics provide more accurate predictions of local failure than bulk mechanics provide. Bulk mechanics were accurate predictors of fissure for the entire sample cohort, but poor predictors of fissure for individual samples. Local strain fields were highly heterogeneous and significant differences were determined between fissured and intact samples, indicating the presence of damage thresholds. In particular, first principal strain rate and maximum shear strain were the best predictors of local failure, as determined by concordance statistics. These data provide an important step in establishing causal links between local mechanics and cartilage damage; ultimately, data such as these can be used to link macro- and micro-scale mechanics and thereby predict mechanically mediated disease on a subject-specific basis.

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“…Fissures proceed to increasing depths into the cartilage matrix following the arcade‐like architecture of the collagen network, that is, originally parallel to the articular surface and then transitioning into the radial orientation, until finally the fissures run along the calcified boundary and cartilage delamination occurs . The probability and severity of surface fissuring following trauma generally increases with higher impact energy, applied stress, stress rate, frequency of dynamic loading, loading duration, and a period of prolonged creep prior to overloading. From a certain impact threshold, in this case an impact energy of 0.25 J imposed on 5 mm diameter cartilage explants, it has even been observed that there was damage to the subchondral bone without macroscopic damage to the cartilage .…”

Section: In Vitro Studies; Short‐term Resultsmentioning

confidence: 99%

“…The reduced constraint from a loosened collagen network on the PGs can also lead to a decreased PG density . An increased glycosaminoglycan (GAG) release and synthesis and decreased content in overloaded samples compared to controls are normally observed from certain threshold loads . However, GAG synthesis tends to decrease at higher loads as cell viability decreases .…”

Section: In Vitro Studies; Short‐term Resultsmentioning

confidence: 99%

Comparison between in vitro and in vivo cartilage overloading studies based on a systematic literature review

Nickien

Heuijerjans

Ito

et al. 2018

Journal Orthopaedic Research

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Methodological differences between in vitro and in vivo studies on cartilage overloading complicate the comparison of outcomes. The rationale of the current review was to (i) identify consistencies and inconsistencies between in vitro and in vivo studies on mechanically‐induced structural damage in articular cartilage, such that variables worth interesting to further explore using either one of these approaches can be identified; and (ii) suggest how the methodologies of both approaches may be adjusted to facilitate easier comparison and therewith stimulate translation of results between in vivo and in vitro studies. This study is anticipated to enhance our understanding of the development of osteoarthritis, and to reduce the number of in vivo studies. Generally, results of in vitro and in vivo studies are not contradicting. Both show subchondral bone damage and intact cartilage above a threshold value of impact energy. At lower loading rates, excessive loads may cause cartilage fissuring, decreased cell viability, collagen network de‐structuring, decreased GAG content, an overall damage increase over time, and low ability to recover. This encourages further improvement of in vitro systems, to replace, reduce, and/or refine in vivo studies. However, differences in experimental set up and analyses complicate comparison of results. Ways to bridge the gap include (i) bringing in vitro set‐ups closer to in vivo, for example, by aligning loading protocols and overlapping experimental timeframes; (ii) synchronizing analytical methods; and (iii) using computational models to translate conclusions from in vitro results to the in vivo environment and vice versa. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:2076–2086, 2018.

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Development of an in vitro model of injury-induced osteoarthritis in cartilage explants from adult horses through application of single-impact compressive overload

Cited by 13 publications

References 59 publications

Synoviocytes protect cartilage from the effects of injury in vitro

Synoviocytes protect cartilage from the effects of injury in vitro

Multiscale Strain as a Predictor of Impact-Induced Fissuring in Articular Cartilage

Comparison between in vitro and in vivo cartilage overloading studies based on a systematic literature review

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