Def6 suppresses osteoblastic differentiation and bone formation through endogenous type I interferon-mediated feedback inhibition

Def6 suppresses osteoblast differentiation and mineralization both in vitro and in vivo. Def6 knockout (KO) mice exhibit osteoporotic phenotype with enhanced osteoclast formation. Osteoblast differentiation and bone formation are elevated as well in Def6 KO mice, indicating a high bone turnover rate that leads to bone loss in Def6 KO mice. Thus, lack of Def6 leads towards unbalanced activities between osteoclastic resorption and osteoblast mediated bone formation and disrupts normal bone remodeling. Def6 suppresses osteoblast differentiation via endogenous type I IFN-mediated feedback inhibition. These findings reveal that Def6 is a novel bone remodeling regulator that controls both osteoclast and osteoblast differentiation to maintain bone remodeling. Overall design: Osteoblastic cells were isolated from the calvarial bone of newborn (0-3d) mice. mRNA profiles of calvarila osteoblsts(day0 and day12) from wild type (WT) and Def6-/- mice were generated by deep sequencing using Illumina Hiseq4000.