Inactivating Mutation in IRF8 Promotes Osteoclast Transcriptional Programs and Increases Susceptibility to Tooth Root Resorption.

ABSTRACT: This is the first study to our knowledge to report a novel mutation in the interferon regulatory factor 8 gene (IRF8^G388S ) associated with multiple idiopathic tooth root resorption, a form of periodontal disease. The IRF8^G388S variant in the highly conserved C-terminal motif is predicted to alter the protein structure, likely impairing IRF8 function. Functional assays demonstrated that the IRF8^G388S mutant promoted osteoclastogenesis and failed to inhibit NFATc1-dependent transcriptional activation when compared with IRF8^WT control. Further, similar to subjects with heterozygous IRF8^G388S mutation, Irf8^+/- mice exhibited increased osteoclast activity in the mandibular alveolar bone surrounding molar teeth. Immunohistochemis

SUBMITTER: Thumbigere-Math V 

PROVIDER: S-EPMC6663587 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature