A graphic user interface for the evaluation of knee osteoarthritis (GEKO): an open-source tool for histological grading

Kloefkorn, Heidi E.; Jacobs, Brittany Y.; Xie, Danny; Allen, Kyle D.

doi:10.1016/j.joca.2018.09.005

Cited by 13 publications

(11 citation statements)

References 12 publications

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“…In 2010, OARSI updated their recommendations for the histological assessment of OA in different species; in the histological assessment schemes for the rat, a number of quantitative measures of joint damage were recommended 35 . Inspired by this quantitative approach, our group developed GEKO 28 , a free and open-source MATLAB package for knee OA histology evaluation. Here, GEKO-based scores were able to identify age-related effects on cartilage damage, partly due to the increased resolution that comes with quantitative measure of cartilage and bone damage.…”

Section: Discussionmentioning

confidence: 99%

“…Since this is the first application of multiplex magnetic capture, our first set of experiments validates this approach in vitro. Next, both the multiplex magnetic capture protocol and our previously published methods to quantitatively evaluate rodent knee histology 28 are used to assess the severity of post-traumatic OA in 3, 6, and 9 month old male Lewis rats. Our methods begin with the respective experimental designs, with detailed methods provided thereafter.…”

Section: Methodsmentioning

confidence: 99%

“…Knees were then sectioned frontally at 10 μm with at least one section acquired every 100 μm between the anterior and posterior horn of the medial meniscus. Slides were stained with safranin-O/fast green and graded using our graphic user interface for the evaluation of knee OA (GEKO) 28 . GEKO is a quantitative histological grading tool based on the OARSI histopathology recommendations for the rat 35 .…”

Section: Histologymentioning

confidence: 99%

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The effects of age on the severity of joint damage and intra-articular inflammation following a simulated medial meniscus injury in 3, 6, and 9 month old male rats

Allen

Chan

Yarmola

et al. 2019

Connective Tissue Research

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Purpose: Aging is a known risk factor for osteoarthritis (OA). Several transgenic rodent models have been used to investigate the effects of accelerated or delayed aging in articular joints. However, age-effects on the progression of post-traumatic OA are less frequently evaluated. The objective of this study is to evaluate how animal age affects the severity of intra-articular inflammation and joint damage in the rat medial collateral ligament plus medial meniscus transection (MCLT+MMT) model of knee OA.Methods: Forty-eight, male Lewis rats were aged to 3, 6, or 9 months old. At each age, eight rats received either an MCLT+MMT surgery or a skin-incision. At 2 months post-surgery, intraarticular evidence of CTXII, IL1β, IL6, TNFα, and IFNγ was evaluated using a multiplex magnetic capture technique, and histological evidence of OA was assessed via a quantitative histological scoring technique.Results: Elevated levels of CTXII and IL6 were found in MCLT+MMT knees relative to skinincision and contralateral controls; however, animal age did not affect the severity of joint inflammation. Conversely, histological investigation of cartilage damage showed larger cartilage lesion areas, greater width of affected cartilage, and more evidence of hypertrophic cartilage damage in MCLT+MMT knees with age.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Histologymentioning

confidence: 99%

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The effects of age on the severity of joint damage and intra-articular inflammation following a simulated medial meniscus injury in 3, 6, and 9 month old male rats

Allen

Chan

Yarmola

et al. 2019

Connective Tissue Research

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“…Slides were stained with toluidine blue; 3 sections per knee were assessed by 3 blinded graders using our histological grading software (GEKO) (30,31). Histological differences between IDO-Gal3 treated and saline treated knees were assessed using Student's t-tests.…”

Section: Histologymentioning

confidence: 99%

Intra-Articular Delivery of an Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein for Osteoarthritis Treatment in Male Lewis Rats

Partain

Bracho‐Sanchez

Farhadi

et al. 2021

Preprint

Self Cite

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Objective: Controlling joint inflammation can improve osteoarthritis (OA) symptoms; however, current treatments often fail to provide long-term effects. We have developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3). IDO converts tryptophan to kynurenines, directing the local environment toward an anti-inflammatory state; Gal3 binds carbohydrates and extends IDO's joint residence time. In this study, we evaluated IDO-Gal3's ability to alter OA-associated inflammation and pain-related behaviors in a rat model of established knee OA. Methods: Joint residence was first evaluated with an analog Gal3 fusion protein (NanoLuc and Gal3, NL-Gal3) that produces luminescence from furimazine. OA was induced in male Lewis rats via a medial collateral ligament and medial meniscus transection (MCLT+MMT). At 8 weeks, NL or NL-Gal3 were injected intra-articularly (n=8 per group), and bioluminescence was tracked for 4 weeks. Next, IDO-Gal3's ability to modulate OA pain and inflammation was assessed. Again, OA was induced via MCLT+MMT in male Lewis rats, with IDO-Gal3 or saline injected into OA-affected knees at 8 weeks post-surgery (n=7 per group). Gait and tactile sensitivity were then assessed weekly. At 12 weeks, intra-articular levels of IL6, CCL2, and CTXII were assessed. Results: The Gal3 fusion increased joint residence in OA and contralateral knees (p<0.0001). In OA-affected animals, IDO-Gal3 improved tactile sensitivity (p=0.002), increased walking velocities (p<0.033), and improved vertical ground reaction forces (p<0.04). Finally, IDO-Gal3 decreased intra-articular IL6 levels within the OA-affected joint (p=0.0025). Conclusion: Intra-articular IDO-Gal3 delivery provided long-term modulation of joint inflammation and pain-related behaviors in rats with established OA.

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“…Detailed methods are available in the supplement. Disease was evaluated by grading Toluidine Blue stained slides using the OARSI scoring system [37] by a blinded grader in the GEKO software developed at the University of Florida (version 7) [38].…”

Section: Histologymentioning

confidence: 99%

Effects of cartilage-targeting moieties on nanoparticle biodistribution in healthy and osteoarthritic joints

et al. 2020

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Understanding intra-articular biodistribution is imperative as candidate osteoarthritis (OA) drugs become increasingly site-specific. Cartilage has been identified as opportunistic for therapeutic intervention, but poses numerous barriers to drug delivery. To facilitate drug delivery to cartilage, nanoscale vehicles have been designed with different features that target the tissue's matrix. However, it is unclear if these targeting strategies are influenced by OA and the associated structural changes that occur in cartilage. The goal of this work was to study the effectiveness of different cartilage-targeting nanomaterials with respect to cartilage localization and retention, and to determine how these outcomes change in OA. To address these questions, a nanoparticle (NP) system was developed, and the formulation was tuned to possess three distinct cartilage-targeting strategies: (1) passive targeting cationic NPs for electrostatic attraction to cartilage, (2) active targeting NPs with binding peptides for collagen type II, and (3) untargeted neutrally-charged NPs. Ex vivo analyses with bovine cartilage explants demonstrated that targeting strategies significantly improved NP associations with both healthy and OA-like cartilage. In vivo studies with collagenase-induced OA in rats revealed that disease state influenced joint biodistribution for all three NP formulations. Importantly, the extent of cartilage accumulation for each NP system was affected by disease differently; with active NPs, but not passive NPs, cartilage accumulation was increased in OA relative to healthy knees. Together, this work suggests that NPs can be strategically designed for site-specific OA drug delivery, but the biodistribution of the NPs are influenced by the disease conditions into which they are delivered.

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A graphic user interface for the evaluation of knee osteoarthritis (GEKO): an open-source tool for histological grading

Cited by 13 publications

References 12 publications

The effects of age on the severity of joint damage and intra-articular inflammation following a simulated medial meniscus injury in 3, 6, and 9 month old male rats

The effects of age on the severity of joint damage and intra-articular inflammation following a simulated medial meniscus injury in 3, 6, and 9 month old male rats

Intra-Articular Delivery of an Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein for Osteoarthritis Treatment in Male Lewis Rats

Effects of cartilage-targeting moieties on nanoparticle biodistribution in healthy and osteoarthritic joints

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