Related Experiment Video
Updated: May 22, 2026
Studying Chronic Exposure of Mice to Ultraviolet B Radiation
Published on: August 19, 2025
Effects on bone by the light/dark cycle and chronic treatment with melatonin and/or hormone replacement therapy in
Paula A Witt-Enderby1, John P Slater, Nakpangi A Johnson
1Division of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA 15282, USA. wittp@duq.edu
Abstract:
In this study, the effects of the light/dark cycle, hormone replacement therapy (HRT), and nocturnal melatonin supplementation on osteogenic markers and serum melatonin levels were examined in a blind mouse model (MMTV-Neu transgenic mice). Melatonin levels in this mouse strain (FVB/N) with retinal degeneration (rd-/-) fluctuate in a diurnal manner, suggesting that these mice, although blind, still perceive light. Real-time RT-PCR analyses demonstrated that Runx2, Bmp2, Bmp6, Bglap, and Per2 mRNA levels coincide with melatonin levels. The effect of chronic HRT (0.5 mg 17β-estradiol + 50 mg progesterone in 1800 kcal of diet) alone and in combination with melatonin (15 mg/L drinking water) on bone quality and density was also assessed by histomorphometry and microcomputed tomography, respectively. Bone density was significantly increased (P < 0.05) after 1 yr of treatment with the individual therapies, HRT (22% increase) and nocturnal melatonin (20% increase) compared to control. Hormone replacement therapy alone also increased surface bone, decreased trabecular space, and decreased the number of osteoclasts without affecting osteoblast numbers compared to the control group (P < 0.05). Chronic HRT + melatonin therapy did not significantly increase bone density, even though this combination significantly increased Bglap mRNA levels. These data suggest that the endogenous melatonin rhythm modulates markers important to bone physiology. Hormone replacement therapy with or without nocturnal melatonin in cycling mice produces unique effects on bone markers and bone density. The effects of these therapies alone and combined may improve bone health in women in perimenopause and with low nocturnal melatonin levels from too little sleep, too much light, or age.
Insights
Hormone replacement therapy (HRT) and nocturnal melatonin supplementation both increased bone density in a blind mouse model. These findings suggest potential benefits for bone health in women experiencing perimenopause or low melatonin levels.
Area of Science:
- Endocrinology
- Bone Biology
- Chronobiology
Background:
- The interplay between circadian rhythms, hormones, and bone metabolism is complex.
- Melatonin, a hormone regulated by light/dark cycles, influences various physiological processes, including bone physiology.
- Blindness in mice does not always abolish circadian melatonin rhythms, offering a model to study its effects.
Purpose of the Study:
- To investigate the impact of hormone replacement therapy (HRT) and nocturnal melatonin on osteogenic markers and bone health in a blind mouse model.
- To determine if endogenous melatonin rhythms influence bone physiology.
- To assess the combined effects of HRT and melatonin on bone density and quality.
Main Methods:
- Utilized a blind mouse model (MMTV-Neu transgenic mice, FVB/N strain with retinal degeneration).
- Administered chronic hormone replacement therapy (HRT) and/or nocturnal melatonin supplementation.
- Assessed osteogenic marker mRNA levels using real-time RT-PCR.
- Evaluated bone quality and density via histomorphometry and microcomputed tomography.
Main Results:
- Both HRT and nocturnal melatonin significantly increased bone density (22% and 20%, respectively) after one year compared to controls.
- HRT alone improved bone surface, reduced trabecular space, and decreased osteoclast numbers.
- Combined HRT and melatonin therapy did not further increase bone density but elevated Bglap mRNA levels.
Conclusions:
- Endogenous melatonin rhythms appear to modulate key markers of bone physiology.
- HRT and nocturnal melatonin, individually, show promise for improving bone density.
- These findings suggest potential therapeutic strategies for bone health in women with hormonal changes or disrupted melatonin production.
