title: 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.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, Måløv, Denmark.|Department of Biology, Copenhagen University, Copenhagen, Denmark.
authors.forename: Heidi S
authors.initials: HS
authors.lastname: Schultz
authors.affiliation: Novo Nordisk Research Centre China CA, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Keller
authors.affiliation: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fleetwood
authors.affiliation: Novo Nordisk Research Centre China CA, Beijing, China.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Sun
authors.affiliation: Novo Nordisk Research Centre China CA, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Novo Nordisk Research Centre China CA, Beijing, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Hamilton
authors.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Olle
authors.initials: O
authors.lastname: Bjørkdahl
authors.affiliation: Department of Biology, Copenhagen University, Copenhagen, Denmark.
authors.forename: Martin W
authors.initials: MW
authors.lastname: Berchtold
authors.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Panina
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000276:immunology*; D010010:Osteoclasts / Q000166:cytology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013582:Synovial Fluid / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; C508606:CXCL8 protein, human; D024042:Collagen Type I; D024043:Collagen Type II; D018836:Inflammation Mediators; D016209:Interleukin-8; C512828:OSCAR protein, human; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha
keywords: Autoimmunity; Collagen; Inflammation; Monocyte; OSCAR; Rheumatoid arthritis