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Colon epithelial cell-specific Bmal1 deletion impairs bone formation in mice
Frank C Ko1, Sarah B Jochum2, Brittany M Wilson3
1Department 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.
Bone
|December 30, 2022
Summary
Disrupting the Bmal1 clock gene in colon cells reduces bone mass in male mice. This highlights the gut
Area of Science:
- Circadian Biology
- Bone Metabolism
- Gastroenterology
Background:
- The circadian clock regulates bone metabolism and skeletal homeostasis.
- Circadian disruption impacts bone mineral density in humans.
- Gut physiology is sensitive to circadian rhythms and influences bone remodeling.
Purpose of the Study:
- To investigate the hypothesis that circadian signaling disruption in colon epithelial cells affects bone.
- To assess the impact of Bmal1 deletion in colon epithelial cells on bone properties.
Main Methods:
- Used Ts4-Cre and Ts4-Cre;Bmal1fl/fl (cBmalKO) mice with colon epithelial cell-specific Bmal1 deletion.
- Assessed structural, functional, and cellular bone properties.
- Analyzed axial and appendicular trabecular bone volume, whole bone mechanics, serum markers, and dynamic histomorphometry.
Main Results:
- Male cBmalKO mice exhibited significantly lower axial and appendicular trabecular bone volume compared to controls.
- Bone mechanical properties were deteriorated in male cBmalKO mice.
- Tissue-level analysis revealed suppressed bone formation with normal resorption in affected mice.
Conclusions:
- Colon epithelial cell-specific deletion of Bmal1 impairs bone acquisition in male mice.
- Circadian signaling in the colon plays a sex-dependent role in maintaining bone mass.
- These findings suggest a gut-bone axis influenced by circadian clock genes.
