Enhanced osteoporotic bone regeneration by strontium-substituted calcium silicate bioactive ceramics
Enhanced osteoporotic bone regeneration by strontium-substituted calcium silicate bioactive ceramics
复制标题
锶取代硅酸钙生物活性陶瓷增强骨质疏松骨再生
DOI：
10.1016/j.biomaterials.2013.09.056
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发表时间：
2013-12-01
期刊：
影响因子：
14
通讯作者：
Chang, Jiang
中科院分区：
文献类型：
--
作者：
Lin, Kaili;Xia, Lunguo;Chang, Jiang
骨质疏松骨骼的再生能力一般低于正常骨骼。目前治疗骨质疏松症骨缺损的方法并不总是令人满意。最近的研究表明，硅酸盐基生物材料可以通过材料释放的硅（Si）离子来刺激成骨和血管生成，并增强体内骨再生。其他研究表明，锶 (Sr) 在抑制骨吸收方面发挥着独特的作用。基于Si和Sr的组合可能对骨质疏松骨再生具有协同作用的假设，开发了结合Sr和Si元素功能的多孔Sr取代硅酸钙（SrCS）陶瓷支架，以促进骨质疏松骨缺损的修复。研究了SrCS离子提取物对卵巢切除大鼠骨髓间充质干细胞（rBMSCs-OVX）成骨分化和人脐静脉内皮细胞（HUVEC）血管生成分化的影响。体外结果表明，在不添加额外的成骨和血管生成试剂的情况下，SrCS释放的Sr和Si离子增强了细胞活力、碱性磷酸酶（ALP）活性、rBMSCs-OVX成骨细胞相关基因的mRNA表达水平和血管内皮生长因子（VEGF）的表达。在 SrCS 提取物中培养的 rBMSCs-OVX 中观察到细胞外信号相关激酶 (ERK) 和 p38 信号通路的激活，并且这些作用可以分别被 ERK 抑制剂 PD98059 和 P38 抑制剂 SB203580 阻断。此外，SrCS的离子提取物刺激HUVEC的增殖、分化和血管生成过程。体内实验表明，SrCS在临界大小的OVX颅骨缺损模型中显着刺激骨再生和血管生成，增强的骨再生可能归因于调节内源性间充质干细胞（MSC）的成骨分化和抑制破骨细胞生成，同时促进内源性间充质干细胞（MSC）的血管生成活性。 内皮细胞（EC）。 (C) 2013 Elsevier Ltd. 保留所有权利。
The regeneration capacity of the osteoporotic bones is generally lower than that of the normal bones. Current methods of bone defect treatment for osteoporosis are not always satisfactory. Recent studies have shown that the silicate based biomaterials can stimulate osteogenesis and angiogenesis due to the silicon (Si) ions released from the materials, and enhance bone regeneration in vivo. Other studies showed that strontium (Sr) plays a distinct role on inhibiting bone resorption. Based on the hypothesis that the combination of Si and Sr may have synergetic effects on osteoporotic bone regeneration, the porous Sr-substituted calcium silicate (SrCS) ceramic scaffolds combining the functions of Sr and Si elements were developed with the goals to promote osteoporotic bone defect repair. The effects of the ionic extract from SrCS on osteogenic differentiation of bone marrow mesenchymal stem cells derived from ovariectomized rats (rBMSCs-OVX), angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) were investigated. The in vitro results showed that Sr and Si ions released from SrCS enhanced cell viability, alkaline phosphatase (ALP) activity, and mRNA expression levels of osteoblast-related genes of rBMSCs-OVX and expression of vascular endothelial growth factor (VEGF) without addition of extra osteogenic and angiogenic reagents. The activation in extracellular signal-related kinases (ERK) and p38 signaling pathways were observed in rBMSCs-OVX cultured in the extract of SrCS, and these effects could be blocked by ERK inhibitor PD98059, and P38 inhibitor SB203580, respectively. Furthermore, the ionic extract of SrCS stimulated HUVECs proliferation, differentiation and angiogenesis process. The in vivo experiments revealed that SrCS dramatically stimulated bone regeneration and angiogenesis in a critical sized OVX calvarial defect model, and the enhanced bone regeneration might be attributed to the modulation of osteogenic differentiation of endogenous mesenchymal stem cells (MSCs) and the inhibition of osteoclastogenesis, accompanying with the promotion of the angiogenic activity of endothelial cells (ECs). (C) 2013 Elsevier Ltd. All rights reserved.