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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 5/2006

Open Access 01-10-2006 | Research article

Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts

Authors: Yukiko Komano, Toshihiro Nanki, Kenji Hayashida, Ken Taniguchi, Nobuyuki Miyasaka

Published in: Arthritis Research & Therapy | Issue 5/2006

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Abstract

Increased bone resorption mediated by osteoclasts causes various diseases such as osteoporosis and bone erosion in rheumatoid arthritis (RA). Osteoclasts are derived from the monocyte/macrophage lineage, but the precise origin remains unclear. In the present study, we show that the purified CD16- human peripheral blood monocyte subset, but not the CD16+ monocyte subset, differentiates into osteoclast by stimulation with receptor activator of NF-κB ligand (RANKL) in combination with macrophage colony-stimulating factor (M-CSF). Integrin-β3 mRNA and the integrin-αvβ3 heterodimer were only expressed on CD16- monocytes, when they were stimulated with RANKL + M-CSF. Downregulation of β3-subunit expression by small interfering RNA targeting β3 abrogated osteoclastogenesis from the CD16- monocyte subset. In contrast, the CD16+ monocyte subset expressed larger amounts of tumor necrosis factor alpha and IL-6 than the CD16- subset, which was further enhanced by RANKL stimulation. Examination of RA synovial tissue showed accumulation of both CD16+ and CD16- macrophages. Our results suggest that peripheral blood monocytes consist of two functionally heterogeneous subsets with distinct responses to RANKL. Osteoclasts seem to originate from CD16- monocytes, and integrin β3 is necessary for osteoclastogenesis. Blockade of accumulation and activation of CD16- monocytes could therefore be a beneficial approach as an anti-bone resorptive therapy, especially for RA.
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Metadata
Title
Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts
Authors
Yukiko Komano
Toshihiro Nanki
Kenji Hayashida
Ken Taniguchi
Nobuyuki Miyasaka
Publication date
01-10-2006
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 5/2006
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2046

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