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

IF 9.6 Q1 ENGINEERING, BIOMEDICAL Biomaterials research Pub Date : 2024-12-09 eCollection Date: 2024-01-01 DOI:10.34133/bmr.0090
Fei Yu, Geng Zhang, Jian Weng, Gaozhi Jia, Chongzhou Fang, Huihui Xu, Ao Xiong, Haotian Qin, Tiantian Qi, Qi Yang, Guangyin Yuan, Hui Zeng, Yuanchao Zhu
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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 P < 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.

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新型鸢尾苷/多孔镁合金支架通过Sirtuin 1-Wnt/β-catenin信号通路修复大鼠骨质疏松性骨缺损
骨质疏松性缺损的骨再生和修复速度慢是临床工作的难点之一。为制备新型淫羊藿苷(ICA)/多孔镁合金支架,探讨其修复骨质疏松性骨缺损的效果及可能机制,采用双侧卵巢切除Sprague-Dawley大鼠。然后,在模型中建立圆柱形骨缺损,制备新型ICA/多孔镁合金支架并植入缺损。修复后8周或12周,采集标本和显微CT数据。显微镜观察采用苏木精和伊红、Goldner、Masson、周期性酸-希夫、天狼星红染色。免疫组化染色检测蛋白表达。新型ICA/多孔镁合金支架无细胞毒性,具有生物安全性。植入缺损8周、12周后,缺损表面颜色、光滑度、深度、面积均优于对照组。ICA/多孔镁合金支架修复的缺损具有充足的类骨组织、较多的矿化骨、较多的胶原纤维和较多的多糖成分。这些条件更接近真实骨骼的条件。修复效果随修复时间的延长而提高。与对照组相比,支架植入缺损8周后,骨组织中SIRT1、Wnt5a、β-catenin、糖原合成酶激酶3β、碱性磷酸酶、矮体相关转录因子2、骨形态发生蛋白-2、骨钙素蛋白的表达水平均升高(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-catenin信号通路来实现。
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