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新型淫羊藿苷/多孔镁合金支架通过沉默调节蛋白1-Wnt/β-连环蛋白信号通路修复大鼠骨质疏松性骨缺损

Repair of Osteoporotic Bone Defects in Rats via the Sirtuin 1-Wnt/β-catenin Signaling Pathway by Novel Icariin/Porous Magnesium Alloy Scaffolds.

作者信息

Yu Fei, Zhang Geng, Weng Jian, Jia Gaozhi, Fang Chongzhou, Xu Huihui, Xiong Ao, Qin Haotian, Qi Tiantian, Yang Qi, Yuan Guangyin, Zeng Hui, Zhu Yuanchao

机构信息

Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, Guangdong, China.

National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China.

出版信息

Biomater Res. 2024 Dec 9;28:0090. doi: 10.34133/bmr.0090. eCollection 2024.

Abstract

The slow rate of bone regeneration and repair in osteoporotic defects is one of the difficulties of clinical work. To prepare a novel icariin (ICA)/porous magnesium alloy scaffold and to investigate its effectiveness and possible mechanism in repairing osteoporotic bone defects, bilateral ovariectomy was performed on Sprague-Dawley rats. Then, a cylindrical bone defect was created in the model, and a novel ICA/porous magnesium alloy scaffold was prepared and implanted into the defect. Eight or 12 weeks after repairing, specimens and micro-computed tomography (CT) data were collected. Microscopic observation was fulfilled through hematoxylin and eosin, Goldner, Masson, periodic acid-Schiff, and Sirius red staining. The expression of proteins was detected by immunohistochemical staining. The novel ICA/porous magnesium alloy scaffold was noncytotoxic and biologically safe. After it was implanted into the defect for 8 or 12 weeks, the surface color and smoothness, depth, and area of the defect were better than those in the control group. Besides, there was sufficient osteoid tissue, more mineralized bones, more collagen fibers, and more polysaccharide components in the defect repaired with the ICA/porous magnesium alloy scaffold. These conditions are closer to those of real bones. Moreover, the repair effect improved with the repair time. Compared with those in the control group, the expression levels of Sirtuin 1(SIRT1), Wnt5a, β-catenin, glycogen synthase kinase 3β, alkaline phosphatase, runt-related transcription factor 2, bone morphogenetic protein-2, and osteocalcin proteins were elevated in bone tissue after the scaffold was implanted into the defect for 8 weeks (all < 0.05). The novel ICA/porous magnesium alloy scaffold promotes the repair of osteoporotic bone defects in rats, a process that may be achieved through activation of the SIRT1-Wnt/β-catenin signaling pathway.

摘要

骨质疏松性骨缺损中骨再生和修复的缓慢速度是临床工作的难题之一。为制备一种新型淫羊藿苷(ICA)/多孔镁合金支架,并研究其修复骨质疏松性骨缺损的有效性及可能机制,对Sprague-Dawley大鼠进行双侧卵巢切除术。然后,在模型中制造圆柱形骨缺损,制备新型ICA/多孔镁合金支架并植入缺损处。修复8周或12周后,收集标本和微型计算机断层扫描(CT)数据。通过苏木精-伊红染色、Goldner染色、Masson染色、过碘酸-希夫染色和天狼星红染色进行显微镜观察。通过免疫组织化学染色检测蛋白表达。新型ICA/多孔镁合金支架无细胞毒性且生物安全性良好。将其植入缺损8周或12周后,缺损处的表面颜色和光滑度、深度及面积均优于对照组。此外,用ICA/多孔镁合金支架修复的缺损处有足够的类骨质组织、更多矿化骨、更多胶原纤维和更多多糖成分。这些情况更接近真实骨骼。而且,修复效果随修复时间而改善。与对照组相比,将支架植入缺损8周后,骨组织中沉默信息调节因子1(SIRT1)、Wnt5a、β-连环蛋白、糖原合酶激酶3β、碱性磷酸酶、 runt相关转录因子2、骨形态发生蛋白-2和骨钙素蛋白的表达水平均升高(均P<0.05)。新型ICA/多孔镁合金支架促进大鼠骨质疏松性骨缺损的修复,这一过程可能通过激活SIRT1-Wnt/β-连环蛋白信号通路来实现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e5a/11625907/3c9c6ac8facd/bmr.0090.fig.001.jpg

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