中华骨质疏松和骨矿盐疾病杂志2026，Vol.19Issue(4)：504-512,9.DOI:10.3969/j.issn.1674-2591.2026.04.009
睡眠剥夺通过CLOCK-BRD4通路加重骨质疏松的作用机制研究
Mechanism of sleep deprivation exacerbating osteoporosis through the CLOCK-BRD4 pathway
摘要
Abstract
Objective To explore the effect of sleep deprivation on bromodomain-containing protein 4(BRD4)acetylation in postmenopausal osteoporosis(PMOP).Methods The PMOP rat model was established by bilateral ovari-ectomy(OVX),and then were divided into two groups with 30 rats in each group.The control group were subjected to a 12-hour light/12-hour dark cycle.The experimental group received artificial light at night(LAN)and the additional light was given from zeitgeber time(ZT)13 to ZT 19.Primary cultured osteoblasts were transfected with Flag-BRD4 overex-pression plasmid or circadian locomotor output cycles kaput(CLOCK)interfering plasmid.Co-immunoprecipitation and Western blot assays were performed to detect the interaction between BRD4 and CLOCK.Results Compared with the control group,OVX rats exposed to LAN exhibited shorter bone length[(40.371±0.147)vs.(38.754±0.078)mm],reduced bone mineral density(BMD)[(0.231±0.016)vs.(0.183±0.024)g/cm2]and decreased bone strength[(9.711±0.754)vs.(9.099±0.272)kg](P＜0.01).Western blot results revealed elevated BRD4 protein expression in the bone tissues of LAN-treated rats.In osteoblasts,the lysine residues K165 and K176 of CLOCK promote BRD4 acetylation.Conclusion Sleep deprivation and estrogen deficiency induce the progression of osteoporosis,and targeting CLOCK-regulated BRD4 acetylation may be a new therapeutic target for the prevention and treatment of PMOP.关键词
睡眠剥夺/绝经后骨质疏松症/含溴结构域蛋白4Key words
sleep deprivation/postmenopausal osteoporosis/bromodomain-containing protein 4分类
医药卫生引用本文复制引用
佘冬梅,孙绍裘,阮红良..睡眠剥夺通过CLOCK-BRD4通路加重骨质疏松的作用机制研究[J].中华骨质疏松和骨矿盐疾病杂志,2026,19(4):504-512,9.基金项目
湖南省自然科学基金医卫联合项目(2025JJ80917) （2025JJ80917）
湖南省中医药科研计划项目(C2024020,E2022027) （C2024020,E2022027）
