Author response: Def6 regulates endogenous type-I interferon responses in osteoblasts and suppresses osteogenesis
Year: 2020
Type: peer-review
Abstract: 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 IFNb 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.
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W3114076343