Positive role of calcium phosphate ceramics regulated inflammation in the osteogenic differentiation of mesenchymal stem cells

Positive role of calcium phosphate ceramics regulated inflammation in the osteogenic differentiation of mesenchymal stem cells
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磷酸钙陶瓷调节炎症在间充质干细胞成骨分化中的积极作用

DOI:
10.1002/jbm.a.36903
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发表时间:
2020
影响因子:
4.9
通讯作者:
Zhang Xingdong
Zhang Xingdong
中科院分区:
工程技术3区
文献类型:
--
作者:
Wang Jing;Chen Xuening;Yang Xiao;Guo Bo;Li Danyang;Zhu Xiangdong;Zhang Xingdong

文献摘要

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近年来,研究证实了炎症反应在钙磷陶瓷诱导成骨中的重要作用,但其内在机制尚不完全清楚。本研究以BCP和β-磷酸三钙陶瓷为材料模型,研究其理化性质对体外炎症反应的影响。结果表明,BCP和β-磷酸三钙均能促进巨噬细胞的黏附、增殖和铺展,促进炎症相关细胞因子(IL-1、IL-6、MCP-1和TNF-α)和生长因子(TGF-β、FGF、PDGF、VEGF、IGF和EGF)的基因表达。BCP对基因表达的促进作用早于β-磷酸三钙。进一步的体外共培养实验表明,预先培养的含有多种细胞因子的CMS能够显著促进MSCs的成骨分化,这从BCP和β-TCP陶瓷刺激下成骨特异性标志物的基因表达和细胞内OCN产物的积累得到证实。进一步的证据发现,矿化结核的形成,在BCM和中医。此外,本研究还揭示了钙磷陶瓷诱导的炎症与其成骨诱导作用之间的关系,即巨噬细胞分泌的细胞因子和生长因子的增加可以促进MSCs的成骨分化。
Recently, researches have confirmed the crucial role of inflammatory response in Ca-P ceramic-induced osteogenesis, however, the underlying mechanism has not yet been fully understood. In this study, BCP and beta-TCP ceramics were used as material models to investigate the effect of physicochemical properties on inflammatory response in vitro. The results showed that BCP and beta-TCP could support macrophages attachment, proliferation, and spreading favorably, as well as promote gene expressions of inflammatory related cytokines (IL-1, IL-6, MCP-1, and TNF-alpha) and growth factors (TGF-beta, FGF, PDGF, VEGF, IGF, and EGF). BCP showed a facilitating function on the gene expressions earlier than beta-TCP. Further coculture experiments performed in vitro demonstrated that the CMs containing various increased cytokines for macrophages pre-culture could significantly promote MSCs osteogenic differentiation, which was confirmed by the gene expressions of osteogenic specific markers and the intracellular OCN product accumulation under the stimulation of BCP and beta-TCP ceramics. Further evidence was found from the formation of mineralized nodules in BCM and TCM. In addition, this study showed a concise relationship between Ca-P ceramic induced inflammation and its osteoinductivity that the increased cytokines and growth factors from macrophages could promote MSCs osteogenic differentiation.