OSCAR-collagen signaling in monocytes plays a proinflammatory role and may contribute to the pathogenesis of rheumatoid arthritis.

Abstract

Osteoclast-associated receptor (OSCAR) is an activating receptor expressed by human myeloid cells. Collagen type I (ColI) and collagen type II (ColII) serve as ligands for OSCAR. OSCAR-collagen interaction stimulates RANK-dependent osteoclastogenesis. We have recently reported that OSCAR promotes functional maturation of monocyte-derived dendritic cells. OSCAR is upregulated on monocytes from rheumatoid arthritis (RA) patients with active disease, and these monocytes show an increased proosteoclastogenic potential. In the current study, we have addressed a functional role for an OSCAR-collagen interaction on monocytes. We show that OSCAR-ColII signaling promoted the survival of monocytes. Moreover, ColII stimulated the release of proinflammatory cytokines by monocytes from healthy donors, which could be completely blocked by an anti-OSCAR monoclonal antibody. Mononuclear cells from the synovial fluid of RA patients plated on ColII secreted TNF-α and IL-8 in an OSCAR-dependent manner. Global RNA profiling showed that components of multiple signaling pathways relevant to RA pathogenesis are regulated at the transcriptional level by OSCAR in monocytes. Thus, OSCAR can play a proinflammatory role in monocyte-derived cells and may contribute crucially on multiple levels to RA pathogenesis.

• Authors: Heidi S Schultz, Li Guo, Pernille Keller, Andrew J Fleetwood, Mingyi Sun, Wei Guo, Chunyan Ma, John A Hamilton, Olle Bjørkdahl, Martin W Berchtold, Svetlana Panina
• Journal: European journal of immunology (Eur J Immunol) Vol. 46 Issue 4 Pg. 952-63 (Apr 2016) ISSN: 1521-4141 [Electronic] Germany
• PMID: 26786702 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antibodies, Monoclonal
• CXCL8 protein, human
• Collagen Type I
• Collagen Type II
• Inflammation Mediators
• Interleukin-8
• OSCAR protein, human
• Receptors, Cell Surface
• Tumor Necrosis Factor-alpha

Topics

• Antibodies, Monoclonal (immunology)
• Arthritis, Rheumatoid (immunology, pathology)
• Cell Differentiation (immunology)
• Cells, Cultured
• Collagen Type I (metabolism)
• Collagen Type II (metabolism)
• Dendritic Cells (immunology)
• Humans
• Inflammation (immunology)
• Inflammation Mediators (metabolism)
• Interleukin-8 (metabolism)
• Monocytes (immunology)
• Osteoclasts (cytology)
• Receptors, Cell Surface (metabolism)
• Signal Transduction (immunology)
• Synovial Fluid (cytology)
• Tumor Necrosis Factor-alpha (metabolism)