osteoprotegerin and Craniofacial-Abnormalities

Skeletal mandibular hypoplasia (SMH), a common type of developmental deformities, results in impaired aesthetics of facial profile, occlusal dysfunction and poor life quality. In this study, BMAL1 deficiency leads to SMH formation, and we aim to investigate the mechanism by which BMAL1 deficiency induces SMH.. Circadian rhythm-disordered mouse models were constructed by placing animals in a jet lag schedule of 6-h light advance every 7 days for 4 or 8 weeks. The OPG expression was evaluated by histomorphometry, immunohistochemistry and western blot analysis. The mechanism by which BMAL1 affects OPG expression was investigated by chromatin immunoprecipitation and luciferase reporter assays. The phenotypes caused by BMAL1 knockout can be rescued by exogenous supplementation with OPG.. We demonstrate that the expressions of BMAL1 and OPG decreased in SMH patients. Circadian rhythm-disordered mice and Bmal1. These results indicate that the circadian clock plays a critical role in the growth and development of mandible by regulating OPG expression, and present a potential therapeutic strategy to prevent SMH.

Topics: Animals; ARNTL Transcription Factors; Cell Differentiation; Child; Circadian Clocks; Craniofacial Abnormalities; Down-Regulation; Humans; Mandibular Diseases; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Osteoclasts; Osteoprotegerin; Promoter Regions, Genetic; Up-Regulation