The Circadian Gene Clock Regulates Bone Formation Via PDIA3.

摘要: The expression patterns of clock-controlled genes (ccgs) are regulated by circadian rhythm, which is a major regulatory and physiological mechanism tied to the solar day. Disruptions in rhythm contribute development cardiovascular diseases, cancer, metabolic syndromes, aging. It has been reported that bone remodeling also rhythm. However, molecular gene Clock regulates yet be elucidated. Here, we show mutant mice exhibit significant reduction density as well increased apoptosis. Protein disulfide isomerase family A member 3 (PDIA3) 1,25-dihydroxy-vitamin D3 [1α,25(OH)2D3] receptor can regulate formation Using luciferase ChIP assays, confirmed Pdia3 ccg. activates transcription binding E-box promoter, decreased ClockΔ19 mice. Forced or completely rescues osteogenic disorders found background inhibits apoptosis vivo vitro. Furthermore, ablation PDIA3 via RNA interference blocks compensatory effect forced osteoblasts. Our results demonstrate core transcriptional control 1,2,5(OH)2D3 PDIA3. © 2016 American Society for Bone Mineral Research.