We have previously reported that when TNF receptor signaling is completely abrogated by genetic deletion, chondrocyte apoptosis is delayed, and we have postulated that this delay interferes with fracture healing.(44) In vivo and in vitro experiments performed here indicate that TNF plays a role in the expression of proapoptotic genes enhanced by diabetes and that TNF-stimulated apoptosis in chondrocytes is mediated by FOXO1. The gene discussed is TNF; the disease is diabetes mellitus.