B7-H3 regulates osteoclast differentiation via type I interferon-dependent IDO inductionopen access
- Authors
- Oh, Younseo; Park, Robin; Kim, So Yeon; Park, Sung-ho; Jo, Sungsin; Kim, Tae-Hwan; Ji, Jong Dae
- Issue Date
- Oct-2021
- Publisher
- SPRINGERNATURE
- Citation
- CELL DEATH & DISEASE, v.12, no.11, pp.1 - 14
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL DEATH & DISEASE
- Volume
- 12
- Number
- 11
- Start Page
- 1
- End Page
- 14
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/140785
- DOI
- 10.1038/s41419-021-04275-6
- ISSN
- 2041-4889
- Abstract
- While their function, as immune checkpoint molecules, is well known, B7-family proteins also function as regulatory molecules in bone remodeling. B7-H3 is a receptor ligand of the B7 family that functions primarily as a negative immune checkpoint. While the regulatory function of B7-H3 in osteoblast differentiation has been established, its role in osteoclast differentiation remains unclear. Here we show that B7-H3 is highly expressed in mature osteoclasts and that B7-H3 deficiency leads to the inhibition of osteoclastogenesis in human osteoclast precursors (OCPs). High-throughput transcriptomic analyses reveal that B7-H3 inhibition upregulates IFN signaling as well as IFN-inducible genes, including IDO. Pharmacological inhibition of type-I IFN and IDO knockdown leads to reversal of B7-H3-deficiency-mediated osteoclastogenesis suppression. Although synovial-fluid macrophages from rheumatoid-arthritis patients express B7-H3, inhibition of B7-H3 does not affect their osteoclastogenesis. Thus, our findings highlight B7-H3 as a physiologic positive regulator of osteoclast differentiation and implicate type-I IFN-IDO signaling as its downstream mechanism.
- Files in This Item
-
- Appears in
Collections - 서울 의과대학 > 서울 내과학교실 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/140785)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.