Abstract
Osteoporosis is a common systemic skeletal metabolism disorder resulting in bone fragility and increased fracture risk. Silent information regulator factor 2 homolog 1 (SIRT1) is crucial in the regulation of several biological processes, including bone metabolism, autophagy, apoptosis, and aging. This study aimed to assess whether the up-regulation of SIRT1 induced by 17beta-estradiol (17β-E2) could promote autophagy and inhibit apoptosis in osteoblasts via the AMPK-mTOR and FOXO3a pathways, respectively. The study found that 17β-E2 (10-6 M) administration induced the up-regulation of SIRT1 in osteoblasts. Up-regulation of SIRT1 induced by 17β-E2 increased the expression level of LC3, Beclin-1, Bcl-2, p-AMPK, FOXO3a but decreased caspase-3 and p-mTOR expression, and then promoted autophagy and inhibited apoptosis. More autophagosomes were observed under a transmission electron microscope (TEM) in 17β-E2 and SRT1720 (a selective SIRT1 activator) co-treated group. When Ex527 (a SIRT1-specific inhibitor) was pretreated, the reversed changes were observed. Taken together, our findings demonstrated that the up-regulation of SIRT1 induced by 17β-E2 could promote autophagy via the AMPK-mTOR pathway and inhibit apoptosis via the FOXO3a activation in osteoblasts, and SIRT1 might become a more significant target in osteoporosis treatment.
Highlights
Osteoporosis is a systemic bone disease, which is characterized by decreased bone mass and deterioration of bone microstructure, resulting in increased bone fragility and enhanced the risk of fracture [1]
To investigate whether up-regulation of Silent information regulator factor homolog 1 (SIRT1) in hFOB1.19 osteoblasts were induced by 17βE2, cells were cultured with different dosages 17β-E2 (0, 10-8, 10-7 and 10-6 M) for 24 h
The results revealed that the expression of light chain 3 (LC3) in osteoblasts cultured with 10-6 M 17β-E2 was significantly increased than that in the control group (Figure 2A)
Summary
Osteoporosis is a systemic bone disease, which is characterized by decreased bone mass and deterioration of bone microstructure, resulting in increased bone fragility and enhanced the risk of fracture [1]. As is known to all, 17β-E2 binds to the specific nuclear estrogen-related receptors (ERRs) ERalpha and ERbeta to exert their physiological functions on cells [10, 11]. Both ERalpha and ERbeta are expressed in bone tissue [12, 13] and bind to 17β-E2 to regulate a multitude of www.aging-us.com physiological processes [10]. Dupont et al found that deficiency of ERalpha was associated with decreased bone turnover and increased trabecular bone volume in male and female mice [16]
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