Itaconate mediates an immunometabolic crosstalk between osteoclasts and osteoblasts

In this report, we show that both glucose and glutamine are essential during OC differentiation, and both contribute to the maintenance of the TCA cycle. Early differentiation is associated with a broken TCA cycle, with IRG1 siphoning TCA intermediates for the production of itaconate, which accumulates extracellularly, stimulating the function of osteoblasts in vitro an in vivo and in vivo and is necessary to retain bone mass in mice. Comparative gene expression profiling analysis of RNA-seq data for bone marrow derived cells treated with MCSF or MCSF+RANKL with or without glutamine or glucose