| First Author | Ng C | Year | 2023 |
| Journal | J Immunol | Volume | 211 |
| Issue | 9 | Pages | 1340-1347 |
| PubMed ID | 37756541 | Mgi Jnum | J:359901 |
| Mgi Id | MGI:7568920 | Doi | 10.4049/jimmunol.2300317 |
| Citation | Ng C, et al. (2023) Jagged1 Acts as an RBP-J Target and Feedback Suppresses TNF-Mediated Inflammatory Osteoclastogenesis. J Immunol 211(9):1340-1347 |
| abstractText | TNF plays a crucial role in inflammation and bone resorption in various inflammatory diseases, including rheumatoid arthritis (RA). However, its direct ability to drive macrophages to differentiate into osteoclasts is limited. Although RBP-J is recognized as a key inhibitor of TNF-mediated osteoclastogenesis, the precise mechanisms that restrain TNF-induced differentiation of macrophages into osteoclasts are not fully elucidated. In this study, we identified that the Notch ligand Jagged1 is a previously unrecognized RBP-J target. The expression of Jagged1 is significantly induced by TNF mainly through RBP-J. The TNF-induced Jagged1 in turn functions as a feedback inhibitory regulator of TNF-mediated osteoclastogenesis. This feedback inhibition of osteoclastogenesis by Jagged1 does not exist in RANKL-induced mouse osteoclast differentiation, as RANKL does not induce Jagged1 expression. The Jagged1 level in peripheral blood monocytes/osteoclast precursors is decreased in RA compared with the nonerosive inflammatory disease systemic lupus erythematosus, suggesting a mechanism that contributes to increased osteoclast formation in RA. Moreover, recombinant Jagged1 suppresses human inflammatory osteoclastogenesis. Our findings identify Jagged1 as an RBP-J direct target that links TNF and Notch signaling pathways and restrains TNF-mediated osteoclastogenesis. Given that Jagged1 has no effect on TNF-induced expression of inflammatory genes, its use may present a new complementary therapeutic approach to mitigate inflammatory bone loss with little impact on the immune response in disease conditions. |
