Notably, single-allele Ikk2 activation in progenitor cells resulted in an approximately 5-fold increase in inflammatory cytokines (Il1b and Tnfa) in fracture callus, which was comparable to the increase observed in patient sera with systemic inflammatory conditions (e.g., aging, obesity, diabetes, and RA) ranging from 2- to more than 40-fold (60–64). Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.