| First Author | Deng Z | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 33373293 | Mgi Jnum | J:300694 |
| Mgi Id | MGI:6490407 | Doi | 10.7554/eLife.59659 |
| Citation | Deng Z, et al. (2020) Def6 regulates endogenous type-I interferon responses in osteoblasts and suppresses osteogenesis. Elife 9:e59659 |
| abstractText | Bone remodeling involves a balance between bone resorption and formation. The mechanisms underlying bone remodeling are not well understood. DEF6 is recently identified as a novel loci associated with bone mineral density. However, it is unclear how Def6 impacts bone remodeling. We identify Def6 as a novel osteoblastic regulator that suppresses osteoblastogenesis and bone formation. Def6 deficiency enhances both bone resorption and osteogenesis. The enhanced bone resorption in Def6(-/-) mice dominates, leading to osteoporosis. Mechanistically, Def6 inhibits the differentiation of both osteoclasts and osteoblasts via a common mechanism through endogenous type-I IFN-mediated feedback inhibition. RNAseq analysis shows expression of a group of IFN stimulated genes (ISGs) during osteoblastogenesis. Furthermore, we found that Def6 is a key upstream regulator of IFNbeta and ISG expression in osteoblasts. Collectively, our results identify a novel immunoregulatory function of Def6 in bone remodeling, and shed insights into the interaction between immune system and bone. |
