Current Rheumatology Reviews

Dr. Serena Guiducci  
Department of Biomedicine, Division of Rheumatology
University of Florence
Florence
Italy

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Circulating Osteoclast Precursors: A Mechanism and a Marker of Erosive Arthritis

Author(s): Lianping Xing, Edward M. Schwarz.

Abstract:

Genetic studies have demonstrated that osteoclasts are essential for focal erosion of bone and cartilage as a consequence of chronic pro-inflammatory cytokine production (TNF, IL-1) in inflammatory arthritis. In these inflamed joints, mature osteoclasts differentiate from circulating osteoclast precursors (OCPs) in response to local increased production of RANKL and pro-inflammatory cytokines. Once activated to resorb calcified matrix, these osteoclasts have a short lifespan (days), and must be continually replaced by bone marrow derived OCPs to achieve focal erosions. Therefore, the peripheral blood OCP frequency may directly determine the severity of bone erosion around inflamed joints. Based on the remarkable advances in our knowledge of osteoclast biology, investigators have been able to model the molecular events that control temporal and spatial regulation of osteoclastogenesis in vivo. Here we review the results of these pre-clinical and clinical studies and provide model of pathogenesis in which pro-inflammatory cytokines produced in the joint feedback on the bone marrow to produce and release elevated numbers of OCP into the circulation, which then home to the inflamed joint. Understanding the regulation of OCP generation and mobilization will provide a new strategy for development of drug targets in the treatment of inflammatory arthritis and other disorders associated with elevated peripheral OCP/myeloid progenitors.

Keywords: osteoclast precursors, rheumatoid arthritis, tumor necrosis factor (tnf), mobilization

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Article Details

VOLUME: 1
ISSUE: 1
Year: 2005
Page: [21 - 28]
Pages: 8
DOI: 10.2174/1573397052954127