Department of Pharmacology, Guangdong Medical University, Zhanjiang, Guangdong, 524023, PR China.
Guangdong Key Laboratory for Research and Development of Natural Drugs, Marine Medical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, 524023, PR China; Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518000, PR China.
Biomed Pharmacother. 2020 Aug;128:110304. doi: 10.1016/j.biopha.2020.110304. Epub 2020 Jun 2.
Aging-induced bone loss is a multifactorial, age-related, and progressive phenomenon among the general population and may further progress to osteoporosis and increase the risk of fractures. Cycloastragenol (CAG), currently the only compound reported that activates human telomerase, is thought to be able to alleviate or delay the symptoms of aging and chronic diseases. Previous research has suggested that CAG may have the potential to alleviate age-related bone loss. However, to date, no research has specifically focused on this aspect. In this study, we aimed to investigate whether CAG could prevent senile osteoporosis, and further reveal its underlying mechanism.
CAG treatment was administrated into two bone loss rat models (D-galactose administration and aging) for 20 weeks and 33 weeks, respectively. Serum biomarkers analyses, bone biomechanical tests, micro-computed tomography assessment, and bone histomorphometry analyses were performed on the bone samples collected at the endpoint, to determine whether CAG could prevent or alleviate age-related bone loss. Proteomic analysis was performed to reveal the changes in protein profiles of the bones, and western blot was used to further verify the identity of the key proteins. The viability, osteoblastic differentiation, and mineralization of MC3T3-E1 cells were also evaluated after CAG treatment in vitro.
The results suggest that CAG treatment improves bone formation, reduces osteoclast number, alleviates the degradation of bone microstructure, and enhances bone biomechanical properties in both d-galactose- and aging-induced bone loss models. CAG treatment promotes viability, osteoblastic differentiation, and mineralization in MC3T3-E1 cells. Proteomic and western blot analyses revealed that CAG treatment increases osteoactivin (OA) expression to alleviate bone loss.
The results revealed that CAG alleviates age-related bone loss and improves bone microstructure and biomechanical properties. This may due to CAG-induced increase in OA expression. In addition, the results support preclinical investigations of CAG as a potential therapeutic medicine for the treatment of senile osteoporosis.
衰老引起的骨丢失是一种普遍存在的、多因素的、与年龄相关的进行性现象，可能进一步发展为骨质疏松症，增加骨折的风险。环黄芪醇（CAG）是目前唯一被报道能激活人类端粒酶的化合物，被认为能够缓解或延缓衰老和慢性病的症状。先前的研究表明，CAG 可能具有缓解与年龄相关的骨丢失的潜力。然而，迄今为止，还没有专门针对这一方面的研究。在这项研究中，我们旨在探讨 CAG 是否可以预防老年性骨质疏松症，并进一步揭示其潜在的机制。
分别用 CAG 对两种骨丢失大鼠模型（D-半乳糖给药和衰老）进行 20 周和 33 周的治疗。在实验终点，对收集的骨样本进行血清生物标志物分析、骨生物力学测试、微计算机断层扫描评估和骨组织形态计量学分析，以确定 CAG 是否可以预防或缓解与年龄相关的骨丢失。蛋白质组学分析用于揭示骨骼蛋白质谱的变化，并用 Western blot 进一步验证关键蛋白的身份。体外 CAG 处理后还评估了 MC3T3-E1 细胞的活力、成骨细胞分化和矿化。
结果表明，CAG 治疗可改善骨形成、减少破骨细胞数量、减轻骨微结构降解，并增强两种 D-半乳糖和衰老诱导的骨丢失模型中的骨生物力学特性。CAG 治疗促进 MC3T3-E1 细胞的活力、成骨细胞分化和矿化。蛋白质组学和 Western blot 分析表明，CAG 治疗通过增加骨激活素（OA）的表达来缓解骨丢失。
结果表明，CAG 可缓解与年龄相关的骨丢失，改善骨微结构和生物力学特性。这可能是由于 CAG 诱导 OA 表达增加所致。此外，这些结果支持 CAG 作为治疗老年性骨质疏松症的潜在治疗药物的临床前研究。
