BROWSE

Related Scientist

Researcher

조재호
면역 미생물 공생 연구단
more info

Cyclic Dinucleotides Inhibit Osteoclast Differentiation Through STING-Mediated Interferon-β Signaling

Cited 0 time in webofscience Cited 0 time in scopus
37 Viewed 10 Downloaded
Title
Cyclic Dinucleotides Inhibit Osteoclast Differentiation Through STING-Mediated Interferon-β Signaling
Author(s)
Yeongkag Kwon; Ok-Jin Park; Jiseon Kim; Jaeho Cho; Cheol-Heui Yun; Seung Hyun Han
Publication Date
2019-07
Journal
JOURNAL OF BONE AND MINERAL RESEARCH, v.34, no.7, pp.1366 - 1375
Publisher
WILEY-BLACKWELL
Abstract
Cyclic dinucleotides (CDNs), such as cyclic diadenylate monophosphate and cyclic diguanylate monophosphate, are commensal bacteria-derived second messengers in the gut that modulate bacterial survival, colonization, and biofilm formation. Recently, CDNs have been discovered to have an immunomodulatory activity by inducing the expression of type I interferon (IFN) through STING signaling pathway in macrophages. Because CDNs are possibly absorbed and delivered into the bone marrow, where bone-resorbing osteoclasts are derived from monocyte/macrophage lineages, CDNs could affect bone metabolism by regulating osteoclast differentiation. In this study, we investigated the effect of CDNs on the differentiation and function of osteoclasts and osteoblasts. When bone marrow-derived macrophages (BMMs) were differentiated into osteoclasts with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) in the presence of CDNs, the differentiation was inhibited by CDNs in a dose-dependent manner. In contrast, CDNs did not influence the differentiation of committed osteoclasts or osteoblast precursors. STING signaling pathway appeared to be critical for CDNs-mediated inhibition of osteoclast differentiation since CDNs induced the phosphorylation of TBK1 and IRF3, a representative feature of STING activation, and osteoclast differentiation was restored in STING knockdown BMMs with siRNA. Moreover, CDNs increased the mRNA expression of STING-meditated IFN-β, which is a negative regulator of osteoclastogenesis. In addition, CDNs also induced the phosphorylation of STAT1, which mediates IFN-α/β receptor (IFNAR) signal transduction. The inhibitory effects of CDNs on osteoclast differentiation were not observed in the presence of antibody blocking IFNAR or in macrophages derived from IFNAR1 -/- mice. Experiments using a mouse calvarial implantation model showed that RANKL-induced bone resorption was inhibited by CDNs. Taken together, these results suggest that CDNs inhibit osteoclast differentiation and bone resorption through induction of IFN-β via the STING signaling pathway. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Researc
URI
https://pr.ibs.re.kr/handle/8788114/5966
ISSN
0884-0431
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
Files in This Item:
Cyclic Dinucleotides Inhibit Osteoclast Differentiation Through STING-Mediated Interferon-β Signaling.pdfDownload

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse