Zhong Mingliang, Wu Zhenyu, Chen Zhixi, Wu Longhuo, Zhou Jianguo
College of Rehabilitation, Gannan Medical University, Ganzhou, 341000, China.
First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.
J Orthop Surg Res. 2024 Mar 11;19(1):179. doi: 10.1186/s13018-024-04665-4.
Cholesterol (CHO) is an essential component of the body. However, high CHO levels in the body can damage bone mass and promote osteoporosis. CHO accumulation can cause osteoblast apoptosis, which has a negative effect on bone formation. The pathogenesis of osteoporosis is a complicate process that includes oxidative stress, endoplasmic reticulum (ER) stress, and inflammation. Geniposide (GEN) is a natural compound with anti-osteoporotic effect. However, the roles of GEN in osteopathogenesis are still unclear. Our previous studies demonstrated that GEN could reduce the accumulation of CHO in osteoblasts and the activation of ER stress in osteoblasts. However, the molecular mechanism of GEN in inhibiting CHO-induced apoptosis in osteoblasts needs to be further investigated.
MC3T3-E1 cells were treated with osteogenic induction medium (OIM). Ethanol-solubilized cholesterol (100 µM) was used as a stimulator, and 10 µM and 25 µM geniposide was added for treatment. The alterations of protein expression were detected by western blot, and the cell apoptosis was analyzed by a flow cytometer.
CHO promoted osteoblast apoptosis by activating ER stress in osteoblasts, while GEN alleviated the activation of ER stress and reduced osteoblast apoptosis by activating the GLP-1R/ABCA1 pathway. Inhibition of ABCA1 or GLP-1R could eliminate the protective activity of GEN against CHO-induced ER stress and osteoblast apoptosis.
GEN alleviated CHO-induced ER stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway.
胆固醇（CHO）是人体的重要组成部分。然而，体内高胆固醇水平会损害骨量并促进骨质疏松症。胆固醇积累会导致成骨细胞凋亡，这对骨形成有负面影响。骨质疏松症的发病机制是一个复杂的过程，包括氧化应激、内质网（ER）应激和炎症。京尼平苷（GEN）是一种具有抗骨质疏松作用的天然化合物。然而，GEN在骨质疏松发病机制中的作用仍不清楚。我们之前的研究表明，GEN可以减少成骨细胞中胆固醇的积累以及成骨细胞中内质网应激的激活。然而，GEN抑制胆固醇诱导的成骨细胞凋亡的分子机制需要进一步研究。
用成骨诱导培养基（OIM）处理MC3T3-E1细胞。使用乙醇溶解的胆固醇（100μM）作为刺激物，并添加10μM和25μM的京尼平苷进行处理。通过蛋白质免疫印迹法检测蛋白质表达的变化，并用流式细胞仪分析细胞凋亡。
胆固醇通过激活成骨细胞中的内质网应激促进成骨细胞凋亡，而京尼平苷通过激活GLP-1R/ABCA1途径减轻内质网应激的激活并减少成骨细胞凋亡。抑制ABCA1或GLP-1R可以消除京尼平苷对胆固醇诱导的内质网应激和成骨细胞凋亡的保护活性。
京尼平苷通过介导GLP-1R/ABCA1途径减轻胆固醇诱导的成骨细胞内质网应激和凋亡。
