ECTS2016 Poster Presentations Cell biology: osteoclasts and bone resorption (35 abstracts)
Human dendritic cell-derived osteoclasts have the ability for both bone absorption and T cell stimulation
Manabu Narisawa 1 , Satoshi Kubo 1 , Shingo Nakayamada 1 , Jidong Zhao 1 , Kei Sakata 2 , Yosuke Okada 1 , Kunihiro Yamaoka 3 & Yoshiya Tanaka 1
1The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyusyu-shi, Japan; 2Mitsubishi Tanabe Pharma Corporation, Yokohama-shi, Japan; 3Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Objective: It is well known that monocytes differentiate into osteoclasts. However, we found that human dendritic cells (DCs) also differentiate to osteoclast-like cells and assessed the role of dendritic cell-derived osteoclast (DC-OC) in pathological processes of inflammatory diseases such as rheumatoid arthritis (RA).
Methods: DC-OCs were differentiated from human monocyte-derived DCs in vitro. The function of DC-OCs was compared to human monocyte-derived osteoclasts (Mo-OCs). Tartrate-resistant acid phosphatase (TRAP) and immunohistochemistry staining were used to detect osteoclasts and DC-OCs in RA synovium.
Results: The culture of human DCs with M-CSF and RANKL in vitro resulted in the differentiation into multi-nucleated DC-OCs, which were positive for OC markers such as TRAP and cathepsin K. These DC-OCs had the strong bone absorption capacity by the Pit-formation assay. On the other hand, DC-OCs expressed major histocompatibility complex-class II and costimulatory molecules such as CD80 and CD86, which were not accompanied in Mo-OCs. Furthermore, co-culturing of DC-OCs with CD4+T cells increased T cell proliferation, whereas Mo-OCs did not, indicating that DC-OCs had antigen-presenting activities. Finally, TRAP-positive multinucleated OCs were detected in RA synovium. Of note, 33% of these cells beard CD86.
Conclusion: This is the first report showing that human DCs can differentiate into DC-OCs in the inflammatory lesion without being regulated by osteoblasts/osteocytes. DC-OCs possess not only the bone resorption ability but also the antigen-presenting function as DC. Actually, there were characteristic osteoclasts bearing costimulatory molecules in RA synovium, indicating that DC-OCs may play a pivotal role in the pathogenesis of RA by the maintenance of inflammation as well as joint destruction.
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Bone Abstracts
ISSN 2052-1219 (online)
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