Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses (original) (raw)
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The Role of Innate Immunity in Osteoarthritis: When Our First Line of Defense Goes On the Offensive
The Journal of rheumatology, 2015
Although osteoarthritis (OA) has existed since the dawn of humanity, its pathogenesis remains poorly understood. OA is no longer considered a "wear and tear" condition but rather one driven by proteases where chronic low-grade inflammation may play a role in perpetuating proteolytic activity. While multiple factors are likely active in this process, recent evidence has implicated the innate immune system, the older or more primitive part of the body's immune defense mechanisms. The roles of some of the components of the innate immune system have been tested in OA models in vivo including the roles of synovial macrophages and the complement system. This review is a selective overview of a large and evolving field. Insights into these mechanisms might inform our ability to identify patient subsets and give hope for the advent of novel OA therapies.
Innate Immune Responses and Osteoarthritis
Current Rheumatology Reports, 2017
Purpose of the Review Osteoarthritis (OA) is a chronic, painful joint disease that affects approximately 40% of adults over 70 year. Age is the strongest predictor of OA, while obesity is considered the primary preventable risk factor for OA. Both conditions are associated with abnormal innate immune inflammatory responses that contribute to OA progression and are the focus of this review. Recent Findings Recent studies have identified risk factors for OA progression including increased innate immune responses secondary to aging-associated myeloid skewing, obesity-related myeloid activation, and synovial tissue hyperplasia with activated macrophage infiltration. Toll-like receptor (TLR)4-induced catabolic responses also play a significant role in OA. Summary The complex interplay between obesity and aging-associated macrophage activation, pro-inflammatory cytokine production from TLR-driven responses, and adipokines leads to a vicious cycle of synovial hyperplasia, macrophage activation, cartilage catabolism, infrapatellar fat pad fibrosis, and joint destruction.
Role of Innate Immune Response Components in the Osteoarthritis
Diyala Journal of Medicine, 2018
Background:Osteoarthritis is a progressive joint disease is mainly worrying on weight bearing in the body, the joints, particularly the knee and hips. Osteoarthritis as an inflammation in the joints must there is an immune defense in the body against this inflammation. This disease that appears primarily in the elderly characterized by erosion articular cartilage, osteophyte, subchondral bone stiffness, synovitis inflammation, many causes of the disease such as age, sex, and obesity, the location of the joi nt injury and various other factors. Objective:To understand the role of innate immune response components in the osteoarthritis, this study was investigated the relation between the innate immune response and osteoarthritis. Patients and Methods:Fifty osteoarthritis patients and fifty healthy persons were participate in this case-control study. The total WBC count, neutrophil percent, lymphocyte percent, monocyte percent, eosinophil percent, basophile percent, platelet number, level of ESR, Level of CRP, and level of C3 complement were investigate in serum and synovial fluid in the osteoarthritis patients and control healthy persons. Results: The results were shown significant elevation in the WBC count, platelet number, level of ESR, level of CRP and level of C3 complement in the serum of osteoarthritis patients compared with control group. A significant positive correlation was shown with weight of patient and the severity of osteoarthritis. The elevation level of C3 complement in the synovial fluid was a significant positive correlation with elevation of level of C3, level of ESR, level of CRP, and WBC count in the serum of patients related to the severity of osteoarthritis status. Conclusion:The results were given an evidence for the crucial role of innate immune response in the defense against osteoarthritis inflammation and any defect in the innate immune component lead to increase the severity of osteoarthritis.
Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review
Osteoarthritis and Cartilage, 2012
Objective: 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. Design: Broad literature search in different databases was performed which resulted in 100 articles. Results: 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. Conclusion: 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.
Molecular pathology of inflammation in osteoarthritis
Inflammation closely concern with pathogenesis of osteoarthritis by promoting expression of important enzymes degrading extracellular matrix of cartilage including collagenases and aggrecanases. However, due to complex mechanism of inflammation, there are many studies to find out the pro-inflammatory agents and responding molecules in osteoarthritis both in vitro and in vivo levels in humans and animal models. This review declares and discusses the role of pro-inflammatory agents and responding molecules secreted by various cell types in joint as well as innate immunity related with inflammation in osteoarthritis.
Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis
Nature reviews. Rheumatology, 2016
Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. Furthermore, we now appreciate that OA pathogenesis involves not only breakdown of cartilage, but also remodelling of the underlying bone, formation of ectopic bone, hypertrophy of the joint capsule, and inflammation of the synovial lining. That is, OA is a disorder of the joint as a whole, with inflammation driving many pathologic changes. The inflammation in OA is distinct from that in rheumatoid arthritis and other autoimmune diseases: it is chronic, comparatively low-grade, and mediated primarily by the innate immune system. Current treatments for OA only control the symptoms, and none has been FDA-approved for the prevention or slowing of disease progression. However, increasing insight into the inflammatory underpinnings of OA holds promise for the development of new, disease-modifying therapies. Indeed,...
Connective tissue research, 2015
Aim of the study The molecular aspects of inflammation were investigated in equine articular cartilage explants using quantitative proteomics. Material and Methods Articular cartilage explants were stimulated with interleukin (IL)-1β in vitro for 25 days, and proteins released into cell culture media were chemically labelled with isobaric mass tags and analysed by liquid chromatography-tandem mass spectrometry. Results A total of 127 proteins were identified and quantified in media from explants. IL-1β-stimulation resulted in an abundance of proteins related to inflammation, including matrix metalloproteinases, acute phase proteins, complement components and IL-6. Extracellular matrix (ECM) molecules were released at different time points and fragmentation of aggrecan and cartilage oligomeric matrix protein was observed at days 3 and 6, similar to early-stage OA in vivo. Degradation products of the collagenous network were observed at days 18 and 22, similar to late-stage OA. Conclu...