BioProject

Irf8 functions as negative regulator of osteoclastogenesis. Genetic deletion of Irf8 in mice results in osteoporosis, a low bone mass state caused by increased osteoclast activity. More...

Irf8 functions as negative regulator of osteoclastogenesis. Genetic deletion of Irf8 in mice results in osteoporosis, a low bone mass state caused by increased osteoclast activity. However, the effects of Irf8 ablation on genome wide regulation of osteoclast-specific genes is unknown. We performed RNA-seq analysis of Irf8-/- and Irf8+/+ bone marrow macrophages (BMMs) prior to (day 0) and after RANKL treatment (day 4 and day 8). Additionally, we have identified a novel IRF8 mutation in humans, that is associated with increased osteoclast activity and susceptibility to Multiple Idiopathic Cervical Root Resorption (MICRR). To gain insights into the functional consequences of human IRF8 mutation (hIRF8G388S) on osteoclastogenesis, we performed RNA-seq analysis of Irf8-/- BMMs transduced with hIRF8WT, hIRF8G388S, and a larger deletion construct hIRF8379-389, followed by RANKL treatment. Comparative studies in Irf8-/- and hIRF8G388S cells show that IRF8 deficiency promotes significant enhancement of osteoclast-specific transcripts. Overall design: RNA-seq analysis of transcriptional changes in BMMs stimulated with MCSF (day 0) and MCSF plus RANKL (day 4 and day 8). Both male and female mice and cells obtained from both genders were analyzed in this study. Less...