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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. Immunohistochemistry illustrated increased NFATc1 expression in the dentoalveolar region of Irf8 -/- and Irf8 +/- mice when compared with Irf8 +/+ controls. Genomewide analyses revealed that IRF8 constitutively bound to regulatory regions of several thousand genes in osteoclast precursors, and genetic aberration of IRF8 significantly enhanced many osteoclast-specific transcripts. Collectively, this study delineates the critical role of IRF8 in defining osteoclast lineage and osteoclast transcriptional program, which may help in better understanding of various osteoclast-mediated disorders, including periodontal disease. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Background: Multiple idiopathic cervical root resorption (MICRR) is a rare entity distinct from pathologic root resorption that occurs as a result of several local and systemic factors., Methods: This report describes a familial pattern of MICRR, including a recently identified case and a 30-year follow-up on previously described cases., Results: The previously reported father (aged 95 years) and son (aged 64 years), and the recently affected daughter (aged 61 years) recounted non-contributory medical history. The resorptive lesions were asymptomatic, unassociated with any predisposing factors, and first identified during the fourth to sixth decades of life. All tooth types were affected, with posterior teeth being affected earlier and with greater frequency; however, distal root surfaces were never affected. The resorptive lesions were progressive in nature, with additional teeth becoming involved as the condition was followed over time. In many instances, surrounding alveolar bone extended into the existing resorptive defects, but without clinical evidence of ankylosis. Gingival tissues, periodontal probing, and tooth mobility were within normal limits. Microcomputed tomography of extracted teeth demonstrated that the lesions were more extensive than clinically evident and rarely invaded the pulp chamber. Histologically, many resorptive lesions were noted along the cementum surface, with evidence of isolated cemental repair. Management of MICRR focused on restoring damaged root surfaces and extracting teeth with extensive root resorption., Conclusions: MICRR is a challenging entity with unknown etiology and a lack of well-established preventive and management strategies. The familial pattern noted in this report necessitates future studies to investigate the role of genetic components in MICRR development.

Background: The etiology of idiopathic cervical root resorption has not been elucidated clearly. However, the process has been linked to trauma, intracanal bleaching, and partial-thickness connective tissue grafts., Methods: This study describes a familial pattern of multiple idiopathic cervical root resorption in a father and son., Results: The father was a healthy 63-year-old white male who presented with the first resorption lesion in 1983. Twenty-seven additional lesions were identified on 16 teeth over 22 years. Five teeth were lost as a result of extensive resorption. The son was a healthy 43-year-old when a resorption lesion was identified in 1993. A lesion identified on another tooth 12 years later resulted in extraction., Conclusions: Close relatives of those affected by multiple idiopathic cervical root resorption should be examined carefully for cervical resorption. This study also showed that early treatment can prevent or delay the need for extraction.