Department of Medical Oncology, First Hospital of China Medical University, Shenyang, China.
Department of Orthopedics, First Hospital of China Medical University, Shenyang, China.
FASEB J. 2022 Sep;36(9):e22491. doi: 10.1096/fj.202200608RR.
Accumulation of lipid substances decreased the activity of osteoblasts. Trehalose is a typical stress metabolite to form a protective membrane on cell surface which has been demonstrated to regulate lipid metabolism. This activity of Trehalose indicates the potential effect of osteoporosis treatment. Our study aimed to determine the therapeutic effect of Trehalose in high fat-induced osteoporosis. We used palmitic acid (PA) to mimic the state of high fat and observed the apoptosis ratio of osteoblasts increased. After adding Trehalose, the apoptosis ratio decreased obviously. Autophagy is a regulatory means involved in the process of apoptosis. We detected the autophagy protein and found that the expression of Beclin-1, Atg5, and LC3 II increased, and p62 decreased after Trehalose treatment. When adding an autophagy inhibitor (3-MA), the expression of Beclin-1, Atg5, and LC3 II decreased, and p62 increased. These results indicated autophagy was an important factor involved in the preventive effect of Trehalose in PA-induced apoptosis. SIRT3 is a mitochondrial gene that can inhibit apoptosis, which has been reported to promote autophagy. We used SIRT3-siRNA to silence the expression of SIRT3 and found the effect of Trehalose was counteracted. The apoptosis ratio increased and the expression of Beclin-1, Atg5, and LC3 II decreased, p62 increased. Additionally, we also fed the mice with a high-fat diet (HFD) and intragastrical Trehalose. The results showed that Trehalose could inhibit the bone mass loss with HFD. Our study revealed the effect and mechanism of Trehalose in the treatment of osteoporosis.
脂类物质的积累降低了成骨细胞的活性。海藻糖是一种典型的应激代谢物，可以在细胞表面形成保护膜，已被证明可以调节脂代谢。海藻糖的这种活性表明了其在骨质疏松治疗中的潜在作用。本研究旨在确定海藻糖在高脂诱导的骨质疏松症中的治疗效果。我们使用棕榈酸（PA）模拟高脂状态，观察到成骨细胞的凋亡比例增加。添加海藻糖后，凋亡比例明显降低。自噬是参与细胞凋亡过程的一种调节手段。我们检测了自噬蛋白，发现海藻糖处理后 Beclin-1、Atg5 和 LC3 II 的表达增加，p62 减少。当添加自噬抑制剂（3-MA）时，Beclin-1、Atg5 和 LC3 II 的表达减少，p62 增加。这些结果表明自噬是海藻糖预防 PA 诱导的细胞凋亡的重要因素。SIRT3 是一种线粒体基因，可抑制细胞凋亡，已被报道可促进自噬。我们使用 SIRT3-siRNA 沉默 SIRT3 的表达，发现海藻糖的作用被抵消。凋亡比例增加，Beclin-1、Atg5 和 LC3 II 的表达减少，p62 增加。此外，我们还给小鼠喂食高脂肪饮食（HFD）并灌胃海藻糖。结果表明，海藻糖可以抑制 HFD 引起的骨量丢失。本研究揭示了海藻糖在骨质疏松症治疗中的作用和机制。
