Synovitis in osteoarthritis: current understanding with therapeutic implications

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Abstract

Modern concepts of osteoarthritis (OA) have been forever changed by modern imaging phenotypes demonstrating complex and multi-tissue pathologies involving cartilage, subchondral bone and (increasingly recognized) inflammation of the synovium. The synovium may show significant changes, even before visible cartilage degeneration has occurred, with infiltration of mononuclear cells, thickening of the synovial lining layer and production of inflammatory cytokines. The combination of sensitive imaging modalities and tissue examination has confirmed a high prevalence of synovial inflammation in all stages of OA, with a number of studies demonstrating that synovitis is related to pain, poor function and may even be an independent driver of radiographic OA onset and structural progression. Treating key aspects of synovial inflammation therefore holds great promise for analgesia and also for structure modification. This article will review current knowledge on the prevalence of synovitis in OA and its role in symptoms and structural progression, and explore lessons learnt from targeting synovitis therapeutically.

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

Piotr Wojdasiewicz, Łukasz Poniatowski, Dariusz Szukiewicz (2014)

Osteoarthritis (OA) is the most common chronic disease of human joints. The basis of pathologic changes involves all the tissues forming the joint; already, at an early stage, it has the nature of inflammation with varying degrees of severity. An analysis of the complex relationships indicates that the processes taking place inside the joint are not merely a set that (seemingly) only includes catabolic effects. Apart from them, anti-inflammatory anabolic processes also occur continually. These phenomena are driven by various mediators, of which the key role is attributed to the interactions within the cytokine network. The most important group controlling the disease seems to be inflammatory cytokines, including IL-1 β , TNF α , IL-6, IL-15, IL-17, and IL-18. The second group with antagonistic effect is formed by cytokines known as anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of OA with respect to inter- and intracellular signaling pathways is still under investigation. This paper summarizes the current state of knowledge. The cytokine network in OA is put in the context of cells involved in this degenerative joint disease. The possibilities for further implementation of new therapeutic strategies in OA are also pointed.

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The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.

Jérémie Sellam, Francis Berenbaum (2010)

Osteoarthritis (OA), one of the most common rheumatic disorders, is characterized by cartilage breakdown and by synovial inflammation that is directly linked to clinical symptoms such as joint swelling, synovitis and inflammatory pain. The gold-standard method for detecting synovitis is histological analysis of samples obtained by biopsy, but the noninvasive imaging techniques MRI and ultrasonography might also perform well. The inflammation of the synovial membrane that occurs in both the early and late phases of OA is associated with alterations in the adjacent cartilage that are similar to those seen in rheumatoid arthritis. Catabolic and proinflammatory mediators such as cytokines, nitric oxide, prostaglandin E(2) and neuropeptides are produced by the inflamed synovium and alter the balance of cartilage matrix degradation and repair, leading to excess production of the proteolytic enzymes responsible for cartilage breakdown. Cartilage alteration in turn amplifies synovial inflammation, creating a vicious circle. As synovitis is associated with clinical symptoms and also reflects joint degradation in OA, synovium-targeted therapy could help alleviate the symptoms of the disease and perhaps also prevent structural progression.

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Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review.

B.J.E. de Lange-Brokaar, A Ioan-Facsinay, G.J.V.M. van Osch … (2012)

Although osteoarthritis (OA) is considered a non-inflammatory condition, it is widely accepted that synovial inflammation is a feature of OA. However, the role of immune cells and their cytokines in OA is largely unknown. This narrative systematic review summarizes the knowledge of inflammatory properties, immune cells and their cytokines in synovial tissues (STs) of OA patients. Broad literature search in different databases was performed which resulted in 100 articles. Of 100 articles 33 solely investigated inflammation in OA ST with or without comparison with normal samples; the remaining primarily focussed on rheumatoid arthritis (RA) ST. Studies investigating different severity stages or cellular source of cytokines were sparse. OA ST displayed mild/moderate grade inflammation when investigated by means of haematoxylin and eosin (H&E) staining. Most frequently found cells types were macrophages, T cells and mast cells (MCs). Overall the number of cells was lower than in RA, although the number of MCs was as high as or sometimes even higher than in RA ST. Cytokines related to T cell or macrophage function were found in OA ST. Their expression was overall higher than in normal ST, but lower than in RA ST. Their cellular source remains largely unknown in OA ST. Inflammation is common in OA ST and characterized by immune cell infiltration and cytokine secretion. This inflammation seems quantitatively and qualitatively different from inflammation in RA. Further research is needed to clarify the role of inflammation, immune cells and their cytokines in the pathogenesis of OA. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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Alexander Mathiessen:

ORCID: http://orcid.org/0000-0002-9696-2081

alexander_mathiessen@hotmail.com

Journal

Journal ID (nlm-ta): Arthritis Res Ther

Journal ID (iso-abbrev): Arthritis Res. Ther

Title: Arthritis Research & Therapy

Publisher: BioMed Central (London )

ISSN (Print): 1478-6354

ISSN (Electronic): 1478-6362

Publication date (Electronic): 2 February 2017

Publication date PMC-release: 2 February 2017

Publication date (Print): 2017

Volume: 19

Electronic Location Identifier: 18

Affiliations

[1 ]ISNI 0000 0004 0512 8628, GRID grid.413684.c, Department of Rheumatology, , Diakonhjemmet Hospital, ; Oslo, Norway

[2 ]ISNI 0000 0004 1936 8403, GRID grid.9909.9, Leeds Institute of Rheumatic and Musculoskeletal Medicine, , University of Leeds, ; Leeds, UK

[3 ]National Institute for Health Research Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK

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Alexander Mathiessen http://orcid.org/0000-0002-9696-2081

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Publisher ID: 1229

DOI: 10.1186/s13075-017-1229-9

PMC ID: 5289060

PubMed ID: 28148295

SO-VID: 43064c16-66f8-45d4-97ac-9752d8bfaeec

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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ScienceOpen disciplines: Orthopedics

Keywords: osteoarthritis,synovitis,pathophysiology,epidemiology,imaging,treatment

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ScienceOpen disciplines: Orthopedics

Keywords: osteoarthritis, synovitis, pathophysiology, epidemiology, imaging, treatment

Synovitis in osteoarthritis: current understanding with therapeutic implications

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Most cited references 61

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

The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.

Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review.

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