Wang Hengjun, Zhao Yunchao, Liu Huan, Zhang Xuelei, Lv Shuquan, Zhou Tingting, Cui Huantian, Zhao Jianyong, Li Xiaoming
Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei Province 050091, China; Department of Orthopedics, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, Hebei Province 061013, China.
Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei Province 050091, China; Department of Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine in Osteoarthrosis Research, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, Hebei Province 061013, China; Department of Diabetes, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, Hebei Province 061013, China.
J Pharm Biomed Anal. 2024 Sep 15;248:116273. doi: 10.1016/j.jpba.2024.116273. Epub 2024 Jun 3.
Glucocorticoid-induced osteoporosis (GIOP) represents the most prevalent form of secondary osteoporosis. Aucubin (AU), a principal active component found in traditional herbal medicines such as Eucommia ulmoides, has been demonstrated to enhance osteoblast differentiation. Nonetheless, the precise therapeutic effects of AU on GIOP and the complex underlying regulatory mechanisms warrant further investigation. We first established a GIOP model in female mice and then assessed the therapeutic effects of AU using micro-CT analysis, biomechanical testing, measurements of serum calcium (Ca) and phosphorus (P) levels, and histological analyses using Hematoxylin and Eosin (HE) and Masson staining. Subsequently, non-targeted metabolomics was employed in order to study the effects of AU on serum metabolites in GIOP mice. The levels of the factors related to these metabolites were quantified using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot analyses. Finally, the effects of AU on osteoblastic and osteoclastic differentiation were examined. We found that AU significantly ameliorated bone microarchitecture and strength in GIOP mice. It mitigated pathological damages such as impairment of trabecular bone structure and reduction in collagen fibers, while concurrently elevating serum levels of Ca and P. Non-targeted metabolomics revealed that Arachidonic acid (AA) metabolism serves as a common pathway between the control and GIOP groups, as well as between the high-dose AU (AUH) and GIOP groups. AU notably upregulates prostaglandin-endoperoxide synthase 2 (PTGS2) and microsomal prostaglandin-E synthase 1 (PTGES) expression and downregulates prostaglandin-H2 D-isomerase (PTGDS) expression. Furthermore, AU treatment increased the expression of runt-related transcription factor 2 (Runx2) and transcription factor Sp7 (Osterix), enhanced serum alkaline phosphatase (ALP) activity, and reduced osteoclast expression. These results indicate that AU is a potential drug for treating GIOP, and its mechanism is related to regulating AA metabolism and promoting osteoblast differentiation. However, the key targets of AU in treating GIOP still need further exploration.
糖皮质激素性骨质疏松症（GIOP）是继发性骨质疏松症最常见的形式。桃叶珊瑚苷（AU）是杜仲等传统草药中的主要活性成分，已被证明可促进成骨细胞分化。然而，AU对GIOP的确切治疗效果及其复杂的潜在调控机制仍有待进一步研究。我们首先在雌性小鼠中建立了GIOP模型，然后使用显微计算机断层扫描分析、生物力学测试、血清钙（Ca）和磷（P）水平测量以及苏木精和伊红（HE）染色及Masson染色的组织学分析来评估AU的治疗效果。随后，采用非靶向代谢组学研究AU对GIOP小鼠血清代谢物的影响。使用实时定量逆转录聚合酶链反应（RT-qPCR）和蛋白质免疫印迹分析对与这些代谢物相关的因子水平进行定量。最后，检测了AU对成骨细胞和破骨细胞分化的影响。我们发现，AU显著改善了GIOP小鼠的骨微结构和骨强度。它减轻了诸如小梁骨结构受损和胶原纤维减少等病理损伤，同时提高了血清Ca和P水平。非靶向代谢组学显示，花生四烯酸（AA）代谢是对照组与GIOP组以及高剂量AU（AUH）组与GIOP组之间的共同途径。AU显著上调前列腺素内过氧化物合酶2（PTGS2）和微粒体前列腺素-E合酶1（PTGES）的表达，并下调前列腺素-H2 D-异构酶（PTGDS）的表达。此外，AU处理增加了 runt相关转录因子2（Runx2）和转录因子Sp7（osterix）的表达，增强了血清碱性磷酸酶（ALP）活性，并减少了破骨细胞表达。这些结果表明，AU是一种治疗GIOP的潜在药物，其机制与调节AA代谢和促进成骨细胞分化有关。然而，AU治疗GIOP的关键靶点仍需进一步探索。
