Development of an in vitro model of feline cartilage degradation

Abstract

Osteoarthritis is the most common arthropathy of mammalian species including cats. Cartilage degradation is central to the disorder and here we present, for the first time, an in vitro model of feline cartilage degradation which will be useful for further studies in this target species. Feline articular cartilage explant cultures were maintained for 28 days and in the presence of oncostatin M with and without interleukin (IL)-17, tumour necrosis factor (TNF), IL-1alpha, or IL-1beta. Media samples and digested cartilage explants were analysed for glycosaminoglycan (GAG) and collagen content. The combination of IL-1beta and OSM, both at 20 ng/ml, was able to promote GAG release to the greatest extent at 14 days. At 28 days, all groups showed relatively high release of GAG. At 14 days, only IL-1beta and OSM in combination were associated with a statistically significant increase in collagen release over and above control tissue. IL-1beta dose-response studies showed that an IL-1beta dose of 10 ng/ml promotes a statistically significant increase in GAG breakdown when used with OSM, and higher doses of IL-1beta did not result in significantly greater response. The model demonstrated both GAG and collagen degradation and will be of use for further understanding of feline cartilage metabolism and for screening of potential structure-modifying agents to be used in cats.

A Microfluidic System for Testing the Responses of Head and Neck Squamous Cell Carcinoma Tissue Biopsies to Treatment with Chemotherapy Drugs

“…This differs from many reported explant cultures that required the use of 5% CO 2 incubators or other complex gaseous parameters. 10,16 The relative simplicity of the set-up in terms of apparatus is an important consideration that should facilitate widespread use of the technology. With minor alterations to the device, we have already demonstrated that liver and cardiac tissues of similar size to the malignant biopsies can be maintained and studied; the latter being electrically stimulated.…”

A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis

“…In this scenario, reliable and predictive in vitro models of AC tissues in healthy and OA conditions play a critical role in advancing the understanding of the physiology, biology, and pathological progression of OA, and will contribute hugely to the development of novel regenerative treatments for OA ( Grenier et al, 2014 ; Johnson et al, 2016 ). A variety of proinflammatory cytokines are commonly used to induce the ECM degradation seen in human OA which involves factors i.e., interleukins (IL-1α, IL-1β, IL-6, IL-8, IL-9) and tumour necrosis factor (TNF-α) ( Gabriel et al, 2010 ; Novakofski et al, 2012 ; Sylvester et al, 2012 ). Amongst them IL-1β, TNF-α and IL-6 are the three cytokines mostly induced in OA pathogenesis and possess a synergic effect: (i) IL-1β, which was found to inhibit Coll II and proteoglycans (PGs) and stimulate the production of MMP1,3,13, (ii) IL-6 to activate NF-kB pathway and downregulate the enzymatic antioxidant defenses in chondrocytes with mitochondria; (iii) TNF-α, which can activate the NF-kB pathway, increase the expression of MMPs, inhibit anabolic molecules, and stimulate chondrocytes apoptosis ( Fan et al, 2007 ; Calich et al, 2010 ; Meliconi et al, 2013 ; Löfgren et al, 2018 ).…”

An In Vitro Engineered Osteochondral Model as Tool to Study Osteoarthritis Environment

“…[16] Also, explants have been used as in vitro models, but their low availability and cell death at the tissue cut edges are noticeable disadvantages. [17] The development of 3D biomimetic models, providing an environment emulating the native one and giving cells with appropriate structure and force, allows to study cell-cell and cell-ECM interactions, overcoming the limitation of 2D models. The homeostasis of both AC and SB tissues is influenced by biological factors and signaling molecules able to cross the demarcation zone between the tissues.…”

“…[ 16 ] Also, explants have been used as in vitro models, but their low availability and cell death at the tissue cut edges are noticeable disadvantages. [ 17 ]…”