Zhang Xin, Lin Xingnan, Liu Tie, Deng Liquan, Huang Yuanliang, Liu Yuelian
Department of Periodontics, Hospital/School of Stomatology, Zhejiang University, Hangzhou, China.
ACTA, Department of Oral Implantology and Prosthetic Dentistry, Research Institute, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan, Netherlands.
Front Pharmacol. 2019 Mar 12;10:201. doi: 10.3389/fphar.2019.00201. eCollection 2019.
Icariin, a typical flavonol glycoside, is the main active component of Herba Epimedii, which was used to cure bone-related diseases in China for centuries. It has been reported that Icariin can be delivered locally by biomaterials and it has an osteogenic potential for bone tissue engineering. Biomimetic calcium phosphate (BioCaP) bone substitute is a novel drug delivery carrier system. Our study aimed to evaluate the osteogenic potential when Icariin was internally incorporated into the BioCaP granules. The BioCaP combined with Icariin and bone morphogenetic protein 2 (BMP-2) was investigated using an MC3T3-E1 cell line. We also investigated its efficacy to repair 8 mm diameter critical size bone defects in the skull of SD male rats. BioCaP was fabricated according to a well-established biomimetic mineralization process. , the effects of BioCaP alone or BioCaP with Icariin and/or BMP-2 on cell proliferation and osteogenic differentiation of MC3T3-E1 cells were systematically evaluated. , BioCaP alone or BioCaP with Icariin and/or BMP-2 were used to study the bone formation in a critical-sized bone defect created in a rat skull. Samples were retrieved for Micro-CT and histological analysis 12 weeks after surgery. The results indicated that BioCaP with or without the incorporation of Icariin had a positive effect on the osteogenic differentiation of MC3T3-E1. BioCaP with Icariin had better osteogenic efficiency, but had no influence on cell proliferation. BioCap + Icariin + BMP-2 showed better osteogenic potential compared with BioCaP with BMP-2 alone. The protein and mRNA expression of alkaline phosphatase and osteocalcin and mineralization were higher as well. , BioCaP incorporate internally with both Icariin and BMP-2 induced significantly more newly formed bone than the control group and BioCaP with either Icariin or BMP-2 did. Micro-CT analysis revealed that no significant differences were found between the bone mineral density induced by BioCaP with icariin and that induced by BioCaP with BMP-2. Therefore, co-administration of Icariin and BMP-2 was helpful for bone tissue engineering.
淫羊藿苷是一种典型的黄酮醇苷，是淫羊藿的主要活性成分，几个世纪以来在中国一直用于治疗与骨骼相关的疾病。据报道，淫羊藿苷可通过生物材料进行局部递送，并且在骨组织工程方面具有成骨潜力。仿生磷酸钙（BioCaP）骨替代物是一种新型的药物递送载体系统。我们的研究旨在评估淫羊藿苷内部掺入BioCaP颗粒时的成骨潜力。使用MC3T3-E1细胞系研究了结合淫羊藿苷和骨形态发生蛋白2（BMP-2）的BioCaP。我们还研究了其修复SD雄性大鼠颅骨直径8mm临界尺寸骨缺损的效果。BioCaP是根据成熟的仿生矿化过程制备的。系统评估了单独的BioCaP或含有淫羊藿苷和/或BMP-2的BioCaP对MC3T3-E1细胞增殖和成骨分化的影响。单独的BioCaP或含有淫羊藿苷和/或BMP-2的BioCaP用于研究大鼠颅骨中创建的临界尺寸骨缺损中的骨形成。术后12周取出样本进行Micro-CT和组织学分析。结果表明，无论是否掺入淫羊藿苷，BioCaP对MC3T3-E1的成骨分化均有积极作用。含有淫羊藿苷的BioCaP具有更好的成骨效率，但对细胞增殖没有影响。与单独含有BMP-2的BioCaP相比，BioCap +淫羊藿苷+ BMP-2显示出更好的成骨潜力。碱性磷酸酶、骨钙素的蛋白质和mRNA表达以及矿化也更高。含有淫羊藿苷和BMP-2的内部掺入BioCaP诱导形成的新骨明显多于对照组以及单独含有淫羊藿苷或BMP-2的BioCaP。Micro-CT分析显示，含有淫羊藿苷的BioCaP诱导的骨矿物质密度与含有BMP-2的BioCaP诱导的骨矿物质密度之间没有显著差异。因此，淫羊藿苷和BMP-2联合给药有助于骨组织工程。
