The Role and Mechanism of SIRT1 in Resveratrol-regulated Osteoblast Autophagy in Osteoporosis Rats

• Published in: Scientific reports Vol. 9; no. 1; pp. 18424 - 15
• Main Authors: Yang, Xuhao, Jiang, Tianlong, Wang, Yu, Guo, Lei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-12-2019; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; 13/2; 13/51; 38; 38/1; 38/32; 38/35; 38/5; 692/163/2743/316/801; 692/4017; Administration, Oral; Aging; AKT protein; Alkaline phosphatase; Animals; Autophagosomes - drug effects; Autophagosomes - metabolism; Autophagy; Bone remodeling; Cell survival; Dexamethasone; Dexamethasone - toxicity; Disease Models, Animal; Gene expression; Hsp60 protein; Humanities and Social Sciences; Humans; Male; Mitophagy - drug effects; multidisciplinary; Osteoblasts; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - pathology; Osteocalcin; Osteoporosis; Osteoporosis - chemically induced; Osteoporosis - drug therapy; Osteoporosis - pathology; Phagocytosis; Rats; Resveratrol; Resveratrol - pharmacology; Resveratrol - therapeutic use; Science; Science (multidisciplinary); Signal transduction; Signal Transduction - drug effects; SIRT1 protein; Sirtuin 1 - metabolism; TOR protein; Transcription
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-44766-3

Osteoporosis is widely regarded as one of the typical aging-related diseases due to the impairment of bone remodeling. The silent information regulator of transcription1 (SIRT1) is a vital regulator of cell survival and life-span. SIRT1 has been shown to be activated by resveratrol treatment, and also has been proved to prevent aging-related diseases such as osteoporosis. However, the role of SIRT1 about autophagy or mitophagy of osteoblasts in resveratrol-regulated osteoporotic rats remains unclear. This study seeks to investigate the role of SIRT1 about autophagy or mitophagy in osteoblasts through PI3K/Akt signaling pathway in resveratrol-regulated osteoporotic rats. The vivo experiment results have revealed that resveratrol treatment significantly improved bone quality and reduced the levels of serum alkaline phosphatase and osteocalcin in osteoporotic rats. Moreover, Western bolt analysis showed that expression of SIRT1, LC3, and Beclin-1 in osteoblasts increased, while
p
-AKT and
p
-mTOR were downregulated in osteoporosis rats with high dose resveratrol treatment. On the other hand, resveratrol treatment increased the SIRT1 activity, LC3 and Beclin-1 mRNA expression in the dexamethasone (DEX)-treated osteoblasts. More mitophagosomes were observed in the DEX-treated osteoblasts with resveratrol. Meanwhile, the TOM20, Hsp60,
p
-Akt and
p
-mTOR activities were decreased in the DEX-treated osteoblasts with resveratrol. Resveratrol treatment did not change the
p
-p38 and
p
-JNK activities in the osteoblasts. These results revealed that resveratrol treatment protected osteoblasts in osteoporosis rats by enhancing mitophagy by mediating SIRT1 and PI3K/AKT/mTOR signaling pathway.