Chronic Sleep Deprivation Impaired Bone Formation in Growing Rats and Down-Regulated PI3K/AKT Signaling in Bone Tissues

Abstract

Background This study aimed to assess the effects of chronic sleep deprivation (CSD) on bone metabolism in growing rats and the likely underlying mechanism. Methods Twenty 5-week-old male Wistar rats and randomly divided into the CSD and normal control (NC) groups after one-week acclimatization. After a 6-week intervention of sleep deprivation, the distal femurs of both groups were harvested for micro-computed tomography scans and histological analysis. Meanwhile, the femur tissues were measured the mRNA and protein expression via RNA sequencing and immunohistochemical analysis. Serum bone turnover markers were evaluated at 0, 2, 4, and 6 weeks. Results CSD impaired the bone growth, showing an imbalance of bone turnover status, dysphasia in the metaphysis growth plate, and deterioration of bone microarchitecture. Further, CSD suppressed bone formation, showing that the expression of osteogenesis-related proteins (col1α1 and osteocalcin) and mRNA ( igf1, bglap, runx2, col1α1, pth1r ) are down-regulated. Differentially expressed genes were detected, and functional enrichment analyses revealed that the PI3K/AKT pathway was significantly down-regulated in the CSD group. Conclusion These results suggest that CSD can significantly impaire bone health, and it may exert these effects in part by suppressing bone formation and osteoblast differentiation, and inactivating the PI3K/AKT signaling pathway.

Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations

“…Sleep is an essential factor in the bone remodeling cycle, where studies have presented a decrease in bone remodeling with an unchanged pace of bone resorption in states of inadequate sleep [34]. Preclinical studies aiming to explore the actions of sleep restriction on bone health in rats presented a signifi-cant decrease in osteoblast activity and osteoid formation in sleep-deprived rats [34,37,38]. Other findings showcased an unchanged bone resorption rate, with a peculiar decrease of osteoclast activity in sleep-deprived rats, contributing to the reduction in bone density facilitating osteopenia [34].…”

Systematic Metabolic Profiling of Mice with Sleep‐Deprivation

“…[2,3] The "sleep debt" caused by chronic sleep deprivation (SD) can be more harmful than people think. [4] SD can cause depression, fear, and other negative emotions, [5,6] reduce movement and balance skills, [7,8] cause memory and cognitive impairments, [9][10][11] increase food attraction and cause obesity, [12,13] diabetes, [14] cardiovascular diseases, cerebrovascular diseases, [15][16][17] and bone diseases, [18] interfere with immune function, [19,20] and cause an increased risk of cancer, [21] and death. [15] The socioeconomic implications of SD are much more significant than we expected.…”