The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis

Wojdasiewicz, Piotr; Poniatowski, Łukasz A.; Szukiewicz, Dariusz

doi:10.1155/2014/561459

Cited by 1,241 publications

(1,240 citation statements)

References 217 publications

(228 reference statements)

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“…These studies have demonstrated the enhanced production of key inflammatory mediators from chondrocytes exposed to OA synovial fluid or the synovium itself, which may act to further stimulate macrophage inflammation. 12,56,57,68,69 Cumulatively, our results agree well with changes seen in early OA and with similar in vitro model systems using NCs.…”

Section: Discussionsupporting

confidence: 88%

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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: Discussionsupporting

confidence: 88%

“…Each of these enzymes and inflammatory cytokines has been shown to be increased in OA. 5,12,56,57 These results demonstrate significant initial phenotypic differences between the NCs and OACs before coculture with macrophages.…”

Section: Initial Chondrocyte and Macrophage Phenotype Before Coculturementioning

confidence: 62%

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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“…Salidroside treatment was found to decrease expression of TNF-α, and IL-6, which further supports our hypothesis. IL-1 β has been proposed as the key cytokine involved in the pathogenesis of osteoarthritis, because it induces inflammatory reactions and catabolic effects independently as well as being combined with other mediators with respect to the articular cartilage and other elements of joints [28]. In this study we observed that salidroside treatment significantly decreases expression of IL-1 β an excellent anti-inflammatory property of salidroside.…”

Section: Discussionsupporting

confidence: 55%

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2017

MOJI

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“…Osteoarthritis (OA) is the most common form with increased prevalence in the aged population and characterized by progressive degeneration of articular cartilage, aberrant chondrocyte maturation, and osteophyte formation in subchondral bone, resulting in remodeling and functional loss of the joint (Zhang and Jordan 2010). Proinflammatory cytokines (TNF-a, IL-1) and matrix metalloproteinases (MMPs) play central roles in OA (Lories and Luyten 2005;Wojdasiewicz et al 2014). Elevated BMP-2 expression was found in articular chondrocytes of OA mouse models (Blaney Davidson et al 2006).…”

Section: Dysregulation Of Tgf-b or Bmp Signaling In Catabolic Bone DImentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

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The transforming growth factor b (TGF-b) family of signaling molecules, which includes TGF-bs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-b family members play different roles in these tissues, and their activities are often balanced with those of other TGF-b family members and by interactions with other signaling pathways. Perturbations in TGF-b family pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems. This review focuses on the role of this family of signaling molecules in the pathologies of connective tissues that manifest in rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm), as well as in more common disorders (e.g., osteoarthritis and osteoporosis). Many of these diseases are caused by or result in pathological alterations of the complex relationship between the TGF-b family of signaling mediators and the extracellular matrix in connective tissues.T he transforming growth factor b (TGF-b) family of cytokines comprises the three TGF-b proteins (TGF-b1, TGF-b2, and TGFb3) and related growth and differentiation factors such as activins, inhibins, bone morphogenic proteins (BMPs), and growth and differentiation factors (GDFs). These molecules play critical roles both in normal development and in several pathological conditions, including inflammation, fibrosis, and cancer (reviewed in Li and Flavell 2006;Gordon and Blobe 2008;Ikushima and Miyazono 2010). This review focuses on the role of these proteins in development and homeostasis of the skeleton and other connective tissues (summarized in Fig. 1) and on the diseases that ensue when these pathways are altered. Aberrant signaling in these pathways has been associated with common connective 6 These authors contributed equally to this work.

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The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis

Cited by 1,241 publications

References 217 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

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TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

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