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SP0135 Myostatin, sclerostin, syndecan and more
  1. T Pap
  1. Institute of Experimental Musculoskeletal Medicine (IEMM), University Münster, Münster, Germany

Abstract

Rheumatoid arthritis (RA) is the prototype of an inflammatory arthritis that is characterized by chronic inflammation, progressive cartilage destruction and bone erosion. Development of RA is marked by the hyperplasia of the synovial membrane as caused by an infiltration and accumulation of inflammatory cells such as macrophages and lymphocytes as well as an increase in the number of resident mesenchymal cells. These fibroblast-like synoviocytes (FLS) are a key part of the local immune system in the joints and integrate signals form different sources into a pathological tissue response. Resorption of the juxtaarticular bone is part of this pathological tissue response and is denoted as focal bone erosion which occurs early in this disease and over time is associated with significant morbidity. Focal bone erosions are observed at the interface of pannus and bone tissue both marginally, where pannus invades cortical bone, and in the immediate subchondral bone, where the pannus invades the marrow space. Many of the cytokines and growth factors implicated in the inflammatory processes are secreted by FLS and have also been demonstrated to impact directly or indirectly on osteoblast and/or osteoclast differentiation and function. However, research of the last years has also identified some novel pathways by which i) osteoclast- mediated bone resorption is regulated and fine-tuned under inflammatory conditions such as in RA and that ii) link inflammatory bone resorption to other features of systemic autoimmunity such as the activation of developmental pathways or muscle weakness. This lecture will review some of these novel mediators and pathways, including members of the Wnt- signalling pathway (e.g. sclerostin), members of the GDF- family of growth differentiation factors (e.g. myostatin) and cells surface anchored proteoglycans (e.g., syndecans). Focusing on the role of these molecules in the FLS-mediated regulation of osteoclastic bone resorption, the lecture will point to general principles of inflammatory bone remodelling and discuss potential therapeutic implications for RA.

Disclosure of Interest None declared

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