Models to define the stages of articular cartilage degradation in osteoarthritis development

Poulet, Blandine

doi:10.1111/iep.12230

Cited by 23 publications

(19 citation statements)

References 57 publications

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“…17 Furthermore, with the recent intensification of social aging and unsatisfactory geriatric nursing, OA has become an issue of global concern. 18 Current intra-articular sodium hyaluronate injections effectively alleviate relieve pain but do not provide a complete cure, while opioid analgesics are addictive and have other side effects meaning that they cannot be widely used. 19 Articular cartilage destruction, hardening, and hyperosteogeny are the main causes of joint pain and motor damage in OA.…”

Section: Discussionmentioning

confidence: 99%

Effects of miR-146a-5p on chondrocyte interleukin-1β-induced inflammation and apoptosis involving thioredoxin interacting protein regulation

Zhao

2020

J Int Med Res

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Objective Osteoarthritis (OA) is a chronic degenerative arthropathy characterized by articular cartilage degeneration, subchondral osteosclerosis, and hyperosteogeny. MicroRNAs (miRNAs) play an important regulatory role in its pathological development, so this study explored the effect and potential mechanism of miR-146a-5p in interleukin (IL)-1β-induced OA cartilage injury. Methods The human chondrosarcoma cell line SW1353 and normal human chondrocytes C28/I2 were stimulated by IL-1β to construct the OA chondrocyte model. miR-146a-5p and thioredoxin interacting protein (TXNIP) expression levels were detected by quantitative real-time (qRT)-PCR and western blot. Their expression was modified by transfecting an miR-146a-5p inhibitor, mimic, and pcDNA-TXNIP. The relationship between miR-146a-5p and TXNIP was analyzed by the dual-luciferase assay, while cell viability, apoptosis, and inflammatory expression were determined by cell counting, TUNEL staining, and ELISA, respectively. Results miR-146a-5p expression was upregulated in SW1353 and C28/I2 cells stimulated by IL-1β. miR-146a-5p knockdown significantly enhanced cell activity, inhibited inflammatory factor expression, and reduced cell apoptosis. The dual-luciferase assay revealed TXNIP as a target gene of miR-146a-5p and suggested that miR-146a-5p promotion of OA damage could be reversed by upregulating TXNIP. Conclusion These results suggest that miR-146a-5p inhibits cell proliferation and promotes apoptosis and the inflammatory response in OA cartilage injury by modulating TXNIP.

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Section: Discussionmentioning

confidence: 99%

Effects of miR-146a-5p on chondrocyte interleukin-1β-induced inflammation and apoptosis involving thioredoxin interacting protein regulation

Zhao

2020

J Int Med Res

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“…In this context, understanding the processes leading to spontaneous OA pathogenesis and associated cartilage degeneration is just as important, since it is the most common form of OA in humans, affecting mainly elderly populations. Spontaneous cartilage degeneration has been reported in the Dunkin Hartley guinea pig (3 months old) [54], the commonly employed C57BL/6 mice with advanced age (> 17 months old) [55], and in the STR/Ort mouse (12 to 20 weeks of age) [56], which shares many similarities to the severity and progressive rate of joint deterioration that occurs in humans [57]. Age-dependent spontaneous degeneration has also been reported in larger species, such as dogs and horses [35,37].…”

Section: Effect Of Genetic Makeup: Spectrum From Endogenous Regeneratmentioning

confidence: 99%

Understanding cartilage protection in OA and injury: a spectrum of possibilities

Masson

Krawetz

2020

BMC Musculoskelet Disord

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Background: Osteoarthritis (OA) is a prevalent musculoskeletal disease resulting in progressive degeneration of the hyaline articular cartilage within synovial joints. Current repair treatments for OA often result in poor quality tissue that is functionally ineffective compared to the hyaline cartilage and demonstrates increased failure rates posttreatment. Complicating efforts to improve clinical outcomes, animal models used in pre-clinical research show significant heterogeneity in their regenerative and degenerative responses associated with their species, age, genetic/epigenetic traits, and context of cartilage injury or disease. These can lead to variable outcomes when testing and validating novel therapeutic approaches for OA. Furthermore, it remains unclear whether protection against OA among different model systems is driven by inhibition of cartilage degeneration, enhancement of cartilage regeneration, or any combination thereof. Main text: Understanding the mechanistic basis underlying this context-dependent duality is essential for the rational design of targeted cartilage repair and OA therapies. Here, we discuss some of the critical variables related to the cross-species paradigm of degenerative and regenerative abilities found in pre-clinical animal models, to highlight that a gradient of regenerative competence within cartilage may exist across species and even in the greater human population, and likely influences clinical outcomes. Conclusions: A more complete understanding of the endogenous regenerative potential of cartilage in a species specific context may facilitate the development of effective therapeutic approaches for cartilage injury and/or OA.

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“…In order to subtract the background (or gap area) the Color Threshold tool was utilized (2). Next, the Color Deconvolution plugin (3) was used to obtain the hematoxylin color channel only in which the cell nuclei could be identified using a threshold for brightness (4). Particle analysis could then be performed based on the binary image attained in the previous step to obtain the cell count per area [cells/mm 2 ].…”

Section: Figure 2: Pipeline For Histomorphometric Analysis (A)mentioning

confidence: 99%

“…The pathogenesis of osteoarthritis (OA) has not been fully understood so far, partly due to the lack of an optimal model system which sufficiently incorporates all aspects of the disease [1,2]. A vast variety of in vivo, ex vivo, in vitro and (to some extent) in silico models for OA already exists, and these all try to mimic the main features of OA pathophysiology including the degradation of extracellular matrix (ECM), inflammation and alterations in cell metabolism, viability and differentiation [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

In vitro and in silico modeling of cellular and matrix-related changes during the early phase of osteoarthritis

Weber

Fischer

Damerau

et al. 2019

Preprint

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Objective: Understanding the pathophysiological processes of osteoarthritis (OA) require adequate model systems. Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific parts of the disease. This study aimed to combine in vitro and in silico modeling to describe cellular and matrix-related changes during the early phase of OA. We developed an in vitro OA model based on scaffoldfree cartilage-like constructs (SFCCs), which was mathematically modeled using a partial differential equation (PDE) system to resemble the processes during the onset of OA.Design: SFCCs were produced from mesenchymal stromal cells and analyzed weekly by histology and qPCR to characterize the cellular and matrix-related composition. To simulate the early phase of OA, SFCCs were treated with interleukin-1β (IL-1β), tumor necrosis factor α (TNFα) and examined after 3 weeks or cultivated another 3 weeks without inflammatory cytokines to validate the regeneration potential. Mathematical modeling was performed in parallel to the in vitro experiments.Results: SFCCs expressed cartilage-specific markers, and after stimulation an increased expression of inflammatory markers, matrix degrading enzymes, a loss of collagen II (Col-2) and a reduced cell density was observed which could be partially reversed by retraction of stimulation. Based on the PDEs, the distribution processes within the SFCCs, including those of IL-1β, Col-2 degradation and cell number reduction was simulated. Conclusions:By combining in vitro and in silico methods, we aimed to develop a valid, efficient alternative approach to examine and predict disease progression and new therapeutic strategies.

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Models to define the stages of articular cartilage degradation in osteoarthritis development

Cited by 23 publications

References 57 publications

Effects of miR-146a-5p on chondrocyte interleukin-1β-induced inflammation and apoptosis involving thioredoxin interacting protein regulation

Effects of miR-146a-5p on chondrocyte interleukin-1β-induced inflammation and apoptosis involving thioredoxin interacting protein regulation

Understanding cartilage protection in OA and injury: a spectrum of possibilities

In vitro and in silico modeling of cellular and matrix-related changes during the early phase of osteoarthritis

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