Abstract
Jdp2 is an AP-1 family transcription factor that regulates the epigenetic status of histones. Previous invitro studies revealed that Jdp2 is involved in osteoclastogenesis. However, the roles of Jdp2 invivo and its pleiotropic functions are largely unknown. Here we generated Jdp2(-/-) mice and discovered itscrucial roles not only in bone metabolism but also in differentiation of neutrophils. Jdp2(-/-) mice exhibited osteopetrosis resulting from impaired osteoclastogenesis. Jdp2(-/-) neutrophils were morphologically normal but had impaired surface expression of Ly6G, bactericidal function, and apoptosis. We also found that ATF3 was an inhibitor of neutrophil differentiation and that Jdp2 directly suppresses itsexpression via inhibition of histone acetylation. Strikingly, Jdp2(-/-) mice were highly susceptible to Staphylococcus aureus and Candida albicans infection. Thus, Jdp2 plays pivotal roles in invivo bone homeostasis and host defense by regulating osteoclast and neutrophil differentiation.
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