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

Abstract

Xiaoye Duan,1,2 Qi Pan,1 Lixin Guo1,2 1Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Lixin Guo, Email [email protected]: 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 (col1α 1 and osteocalcin) and mRNA (igf1, bglap, runx2, col1α 1, 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.Keywords: chronic sleep deprivation, sleep loss, growth, bone formation, RNA sequencing, PI3K/AKT pathway

Keywords

• chronic sleep deprivation
• sleep loss
• growth
• bone formation
• rna sequencing
• pi3k/akt pathway