| First Author | Oh Y | Year | 2021 |
| Journal | Cell Death Dis | Volume | 12 |
| Issue | 11 | Pages | 971 |
| PubMed ID | 34671026 | Mgi Jnum | J:332446 |
| Mgi Id | MGI:6784438 | Doi | 10.1038/s41419-021-04275-6 |
| Citation | Oh Y, et al. (2021) B7-H3 regulates osteoclast differentiation via type I interferon-dependent IDO induction. Cell Death Dis 12(11):971 |
| abstractText | 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. |
