The Adipokine Network in Rheumatic Joint Diseases

Abstract

Rheumatic diseases encompass a diverse group of chronic disorders that commonly affect musculoskeletal structures. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common, leading to considerable functional limitations and irreversible disability when patients are unsuccessfully treated. Although the specific causes of many rheumatic conditions remain unknown, it is generally accepted that immune mechanisms and/or uncontrolled inflammatory responses are involved in their etiology and symptomatology. In this regard, the bidirectional communication between neuroendocrine and immune system has been demonstrated to provide a homeostatic network that is involved in several pathological conditions. Adipokines represent a wide variety of bioactive, immune and inflammatory mediators mainly released by adipocytes that act as signal molecules in the neuroendocrine-immune interactions. Adipokines can also be synthesized by synoviocytes, osteoclasts, osteoblasts, chondrocytes and inflammatory cells in the joint microenvironment, showing potent modulatory properties on different effector cells in OA and RA pathogenesis. Effects of adiponectin, leptin, resistin and visfatin on local and systemic inflammation are broadly described. However, more recently, other adipokines, such as progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin, have been recognized to display immunomodulatory actions in rheumatic diseases. This review highlights the latest relevant findings on the role of the adipokine network in the pathophysiology of OA and RA.

Keywords: adipokine; inflammation; osteoarthritis; rheumatic diseases; rheumatoid arthritis.

Figure 1

Graphical schematic representation of the role of classic and novel adipokines in two rheumatic diseases: osteoarthritis (OA) and rheumatoid arthritis (RA). A variety of adipokines produced by adipose tissue (blue line of arrows) as well as by chondrocytes, osteoclasts, osteoblasts, synoviocytes and inflammatory cells (blue dashed line and blue line formed by arrows), contribute to multiple pathological mechanisms (solid arrows) involved in the development of OA and RA. Although there are differences between the pathogenesis of OA and RA, common mechanisms have also been identified that affect cartilage extracellular matrix (ECM) integrity, dysregulation of bone metabolism, the pathogenic phenotype of synovial fibroblasts and macrophages, modulation of the immune system and synovial angiogenesis. Depending on the context, both pro- and anti-inflammatory effects have been associated with some adipokines, such as visfatin and resistin. Adipokines with a dominant pro-inflammatory role in arthritis are shown with a light red background, whereas those in which an anti-inflammatory action predominates are shown with a green background.