Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)

SummaryOsteoarthritis (OA) has long been considered a “wear and tear” disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading to increased pressure on one particular joint or fragility of cartilage matrix. Progress in molecular biology in the 1990s has profoundly modified this paradigm. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an “inflammatory” theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. Recent experimental data have shown that subchondral bone may have a substantial role in the OA process, as a mechanical damper, as well as a source of inflammatory mediators implicated in the OA pain process and in the degradation of the deep layer of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review

Human chondrocyte culture models for studying cyclooxygenase expression and prostaglandin regulation of collagen gene expression

AbstractObjectiveSince articular chondrocytes and synovial fibroblasts are particularly responsive to interleukin-1 (IL-1) with respect to stimulation of prostaglandin E2(PGE2) biosynthesis, we have used them as models to examine feedback modulatory effects of PGE2, which blocks or attenuates the direct effects of IL-1β on cell-specific collagen gene expression.MethodsImmortalized human chondrocytes were developed for studying responses to cytokines and prostaglandins. Regulatory sequences of the type II collagen gene (COL2A1) in reporter gene constructs were analyzed in transient transfection experiments. Endogenous expression of COL2A1 mRNA, as well as aggrecan, biglycan, and decorin mRNAs, and IL-1-inducible cyclooxygenase (COX-2), phospholipase A2 (PLA2), and inducible nitric oxide synthetase (iNOS) mRNAs were analyzed by RT-PCR.ResultsPrevious work has shown that IL-1β inhibits, while prostaglandins stimulate COL2A1 expression. In different immortalized chondrocyte cell lines, the ability to respond to IL-1β with increased levels of COX-2, PLA2, and iNOS mRNAs depends upon expression of the differentiated chrondrocyte phenotype.ConclusionsOur studies suggest that some IL-1-induced responses in chondrocytes may require differentiation-specific transcription factors that could serve as therapeutic targets for arthritis

Osteoarthritis year in review 2019: epidemiology and therapy

Over the past year many studies and clinical trials have been published in the osteoarthritis (OA) field. This review is based on systematic literature review covering the period May 1st, 2018 to April 19th , 2019; the final selection of articles was subjective. Specifically those articles considered to be presenting novel insights and of potential importance for clinical practice, are discussed.Further evidence has emerged that OA is a serious disease with increasing impact worldwide. Our understanding of development of pain in OA has increased. Detailed studies investigating widely used pharmacological treatments have shown the benefits to be limited, whereas the risks seem higher than expected, suggesting further studies and reconsideration of currently used guidelines. Promising new pharmacological treatments have been developed and published, however subsequent studies are warranted. While waiting for new treatment modalities to appear joint replacement is an effective alternative; new data have become available on how long they might last. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.Pathophysiology and treatment of rheumatic disease

Vitamin K and osteoarthritis: is there a link?

Pathophysiology and treatment of rheumatic disease