Targets, models and challenges in osteoarthritis research

Thysen, Sarah; Luyten, Frank P.; Lories, Rik

doi:10.1242/dmm.016881

Cited by 203 publications

(178 citation statements)

References 175 publications

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“…5 In vitro models that recapitulate key alterations associated with OA may enable the controlled investigation of cell-cell interactions and signaling mechanisms involved in OA, potentially allowing for improved understanding of OA disease progression at the cellular level and for the development of new therapeutics. 73 Toward this eventual goal, we developed a fully 3D in vitro hydrogel-based system (Fig. 1A) that permits the independent evaluation of chondrocyte and macrophage phenotype in coculture, while concurrently allowing us to probe paracrine signaling between the two cell types.…”

Section: Discussionmentioning

confidence: 99%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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The goal of the present study was to develop a fully three-dimensional (3D) coculture system that would allow for systematic evaluation of the interplay between activated macrophages (AMs) and chondrocytes in osteoarthritic disease progression and treatment. Toward this end, our coculture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs)-in two-dimensional (2D) or 3D-with proinflammatory AMs in 2D. In this work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to mimic the native 3D environments of both cell types within the osteoarthritic joint. As with previous studies, increases in matrix metalloproteinases (MMPs) and proinflammatory cytokines associated with the early stages of osteoarthritis were observed during NC-AM coculture, as were decreases in protein-level Aggrecan and collagen II. Thereafter, the coculture system was extended to osteoarthritic chondrocytes (OACs) and AMs to evaluate the potential effects of AMs on pre-existing osteoarthritic phenotypes. OACs in coculture with AMs expressed significantly higher levels of MMP-1, MMP-3, MMP-9, MMP-13, IL-1b, TNF-a, IL-6, IL-8, and IFN-g compared to OACs in mono-culture, indicating that proinflammatory macrophages may intensify the abnormal matrix degradation and cytokine secretion already associated with OACs. Likewise, AMs cocultured with OACs expressed significantly more IL-1b and VEGF-A compared to AM mono-culture controls, suggesting that OACs may intensify abnormal macrophage activation. Finally, OACs cultured in the presence of nonactivated macrophages produced lower levels of MMP-9 and proinflammatory cytokines IL-1b, TNF-a, and IFN-g compared to OACs in the OAC-AM system, results that are consistent with anti-inflammatory agents temporarily reducing certain OA symptoms. In summary, the 3D coculture system developed herein captures several key features of inflammatory OA and may prove useful in future screening of therapeutic agents and/or assessment of disease progression mechanisms.

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Section: Discussionmentioning

confidence: 99%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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show abstract

“…Spontaneous development of OA occurs in guinea pig and spontaneous joint degeneration has been reported in C57 black mice from 3 to 16 months of age 7,8 . Spontaneous OA models do not involve any intervention to induce the condition, but they have inherent variability, and as such, incur greater numbers and cost 9,10 . Chemically induced models, on the other hand, require much less invasive procedures than surgical models, and as such, are easier to implement and permit the study of OA lesions at different stages.…”

Section: Introductionmentioning

confidence: 99%

The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse

Pitcher

Valente

Malcangio

2016

JoVE

105

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A major symptom of patients with osteoarthritis (OA) is pain that is triggered by peripheral as well as central changes within the pain pathways. The current treatments for OA pain such as NSAIDS or opiates are neither sufficiently effective nor devoid of detrimental side effects. Animal models of OA are being developed to improve our understanding of OA-related pain mechanisms and define novel pharmacological targets for therapy. Currently available models of OA in rodents include surgical and chemical interventions into one knee joint. The monoiodoacetate (MIA) model has become a standard for modelling joint disruption in OA in both rats and mice. The model, which is easier to perform in the rat, involves injection of MIA into a knee joint that induces rapid pain-like responses in the ipsilateral limb, the level of which can be controlled by injection of different doses. Intra-articular injection of MIA disrupts chondrocyte glycolysis by inhibiting glyceraldehyde-3-phosphatase dehydrogenase and results in chondrocyte death, neovascularization, subchondral bone necrosis and collapse, as well as inflammation. The morphological changes of the articular cartilage and bone disruption are reflective of some aspects of patient pathology. Along with joint damage, MIA injection induces referred mechanical sensitivity in the ipsilateral hind paw and weight bearing deficits that are measurable and quantifiable. These behavioral changes resemble some of the symptoms reported by the patient population, thereby validating the MIA injection in the knee as a useful and relevant pre-clinical model of OA pain.The aim of this article is to describe the methodology of intra-articular injections of MIA and the behavioral recordings of the associated development of hypersensitivity with a mind to highlight the necessary steps to give consistent and reliable recordings.

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“…Worldwide estimates indicate that OA affects >10% population aged >60 years; however, the impact of this health condition is still underestimated. Genetic factors, joint trauma, and lifestyle-associated risk factors (such as obesity and excessive joint use in occupational or leisurely activities) can contribute to the onset and progression of OA [16]. In humans, aging triggers many changes in all the systems of the body.…”

Section: Resultsmentioning

confidence: 99%

Assesment of Disabled Geriatric Health Council Reports

Şahin¹,

Kırlı²,

İnanç³

et al. 2016

Ann Clin Anal Med

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ÖzetAmaç: Bu çalışmada, 65 yaş ve üzeri, özürlü sağlık kuruluna başvuran olguların değerlendirilmesi amaçlandı. Gereç ve Yöntem: Çalışmada, özürlü kuruluna başvuran, 3112 olgu retrospektif tarandı, 601 olguya ait dosyalar değer-lendirildi. Bulgular: Başvuruların %53,1'i erkek, %46,9'u kadındır. Ortalama yaş 60 (59± 18,35)'dir. En sık başvuru sebebi, sosyal hizmetler %45,6, özürlü-lük oranının tespiti %21,6'dir. 65 yaş ve üzerinde, hipertansiyon %21,6; diyabet %12,6; kronik obstruktif akciğer hastalığı ve dilate kardiyomyopati %3,7 ile ilk sıralardadır (p<0.05). Malignensi 65 yaş ve üzerinde %1,8'di (p>0.05).Dahili özürlülük oranı istatistiksel anlamlı değilken, toplam özürlülük oranı 65 yaş ve üzerinde anlamlıdır (p<0.05). Ek branş patolojileri 65 yaş ve üzerin-de anlamlıdır (p<0.05). Tartışma: Beklenen yaşam süresinin uzaması ve toplumdaki yaşlı bireylerin sayısındaki artış ile, özürlü yaşlı bireylerin sayısında bir artış olmaktadır. Kronik hastalık tanısı almak, geriatrik hasta populasyonu için, hayatın sonu olmamalıdır. Geriatrik populasyonun ruh hali, sosyal yaşa-mı, genel sağlık ve zihinsel sağlık düzeyleri en üst düzeyde tutulmalıdır. Yaşlı hastaların, özel ihtiyaçlarına, özel önem verilerek, imkanların daha geniş kullanımı sağlanmalıdır. Anahtar KelimelerKronik Hastalıklar; Engellilik Değerlendirmesi; Yaşlılar; Muğla; Turkiye Abstract Aim: In this study it is aimed to evaluate geriatric patients who apply to health council. Material and Method: The study retrospectively assessed 3112 patients admitted to the disability ward, of which 601 patients were included in the study. Results: Of the 601 patients, 53.1% were men and 46.9% were women. The mean age of these patients was 60 (std ± 18.35) years. Some of the reasons for admission in the hospital were need for social services (45.6%) and determination of disability rate (21.6%). Most common diseases in patients aged ≥65 years were hypertension (21.6%), diabetes (12.6%), and chronic obstructive lung disease and dilated cardiomyopathy (3.7%; p < 0.05). Malignancy was detected in 1.8% patients aged ≥65 years; however, its prevalence was not statistically significant (p > 0.05). Internal disability rate was not statistically significant (p > 0.05), but total disability was statistically significant (p < 0.05). Moreover, prevalence of additional conditions was statistically significant (p < 0.05) in patients aged ≥65 years. Discussion: Rapid increases in life expectancy and number of older people has increased the prevalence of disabilities among older people. Being diagnosed with chronic diseases should not be the end of life for geriatric populations. Their mood, social life, general health, and mental profile should progress. Sufficient attention should be paid to the special needs of older patients thereby leading to a wider use of facilities.

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Targets, models and challenges in osteoarthritis research

Cited by 203 publications

References 175 publications

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse

Assesment of Disabled Geriatric Health Council Reports

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