Medical College of Soochow University, Suzhou, 215123, China.
Department of Orthopedics, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.
J Orthop Surg Res. 2023 Aug 30;18(1):641. doi: 10.1186/s13018-023-04125-5.
BACKGROUND: Osteoporosis (OP), due to microarchitectural alterations, is associated with decreased bone mass, declined strength, and increased fracture risk. Increased osteoblast apoptosis contributes to the progression of OP. Natural compounds from herbs provide a rich resource for drug screening. Our previous investigation showed that geniposide (GEN), an effective compound from Eucommia ulmoides, could protect against the pathological development of OP induced by cholesterol accumulation. METHODS: The rat OP models were duplicated. Dual-energy X-ray absorptiometry, hematoxylin and eosin staining, and immunohistochemistry were used to evaluate bone changes. TUNEL/DAPI staining assays were used for cell apoptosis detection. Protein expression was determined by western blotting assays. RESULTS: A high-fat diet promoted OP development in vivo, and OX-LDL stimulated osteoblast apoptosis in vitro. GEN exhibited protective activities against OX-LDL-induced osteoblast apoptosis by increasing the NRF2 pathway and decreasing the NF-κB pathway. PDTC, an NF-κB inhibitor, could further promote the biological functions of GEN. In contrast, ML385, an NRF2 inhibitor, might eliminate GEN's protection. CONCLUSION: GEN suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway.
背景：骨质疏松症（OP）由于微观结构的改变，与骨量减少、骨强度下降和骨折风险增加有关。成骨细胞凋亡增加促进了 OP 的进展。草药中的天然化合物为药物筛选提供了丰富的资源。我们之前的研究表明，来自杜仲的有效化合物京尼平苷（GEN）可以预防胆固醇积累引起的 OP 的病理性发展。
方法：复制大鼠 OP 模型。双能 X 射线吸收法、苏木精和伊红染色和免疫组织化学用于评估骨变化。TUNEL/DAPI 染色检测用于细胞凋亡检测。通过 Western 印迹检测蛋白表达。
结果：高脂肪饮食促进体内 OP 的发展，OX-LDL 刺激体外成骨细胞凋亡。GEN 通过增加 NRF2 途径和减少 NF-κB 途径对 OX-LDL 诱导的成骨细胞凋亡表现出保护作用。NF-κB 抑制剂 PDTC 可以进一步促进 GEN 的生物学功能。相比之下，NRF2 抑制剂 ML385 可能消除 GEN 的保护作用。
结论：GEN 通过调节 NRF2/NF-κB 信号通路抑制 OX-LDL 诱导的成骨细胞凋亡。
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