Colon epithelial cell-specific Bmal1 deletion impairs bone formation in mice.

Autor: Ko FC; Department of Anatomy& Cell Biology, Rush University Medical Center, Chicago, IL 60612, United States of America; Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, United States of America; Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, United States of America. Electronic address: frank_ko@rush.edu., Jochum SB; Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, United States of America., Wilson BM; Department of Anatomy& Cell Biology, Rush University Medical Center, Chicago, IL 60612, United States of America., Adra A; Department of Anatomy& Cell Biology, Rush University Medical Center, Chicago, IL 60612, United States of America., Patel N; Department of Anatomy& Cell Biology, Rush University Medical Center, Chicago, IL 60612, United States of America., Lee H; Department of Anatomy& Cell Biology, Rush University Medical Center, Chicago, IL 60612, United States of America., Wilber S; Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, United States of America., Shaikh M; Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, United States of America., Forsyth C; Department of Anatomy& Cell Biology, Rush University Medical Center, Chicago, IL 60612, United States of America; Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, United States of America; Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, United States of America., Keshavarzian A; Department of Anatomy& Cell Biology, Rush University Medical Center, Chicago, IL 60612, United States of America; Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, United States of America; Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, United States of America., Swanson GR; Department of Anatomy& Cell Biology, Rush University Medical Center, Chicago, IL 60612, United States of America; Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, United States of America; Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, United States of America., Sumner DR; Department of Anatomy& Cell Biology, Rush University Medical Center, Chicago, IL 60612, United States of America; Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, United States of America; Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, United States of America.
Jazyk: angličtina
Zdroj: Bone [Bone] 2023 Mar; Vol. 168, pp. 116650. Date of Electronic Publication: 2022 Dec 28.
DOI: 10.1016/j.bone.2022.116650
Abstrakt: The circadian clock system regulates multiple metabolic processes, including bone metabolism. Previous studies have demonstrated that both central and peripheral circadian signaling regulate skeletal growth and homeostasis in mice. Disruption in central circadian rhythms has been associated with a decline in bone mineral density in humans and the global and osteoblast-specific disruption of clock genes in bone tissue leads to lower bone mass in mice. Gut physiology is highly sensitive to circadian disruption. Since the gut is also known to affect bone remodeling, we sought to test the hypothesis that circadian signaling disruption in colon epithelial cells affects bone. We therefore assessed structural, functional, and cellular properties of bone in 8 week old Ts4-Cre and Ts4-Cre;Bmal1 fl/fl (cBmalKO) mice, where the clock gene Bmal1 is deleted in colon epithelial cells. Axial and appendicular trabecular bone volume was significantly lower in cBmalKO compared to Ts4-Cre 8-week old mice in a sex-dependent fashion, with male but not female mice showing the phenotype. Similarly, the whole bone mechanical properties were deteriorated in cBmalKO male mice. The tissue level mechanisms involved suppressed bone formation with normal resorption, as evidenced by serum markers and dynamic histomorphometry. Our studies demonstrate that colon epithelial cell-specific deletion of Bmal1 leads to failure to acquire trabecular and cortical bone in male mice.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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