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脱细胞羊膜基质对人牙髓根尖乳头细胞成骨分化及 ERK1/2 信号通路的影响。

The effects of acellular amniotic membrane matrix on osteogenic differentiation and ERK1/2 signaling in human dental apical papilla cells.

机构信息

School of Dentistry, National Taiwan University, Taipei, Taiwan.

出版信息

Biomaterials. 2012 Jan;33(2):455-63. doi: 10.1016/j.biomaterials.2011.09.065. Epub 2011 Oct 10.

Abstract

The amniotic membrane (AM) has been widely used in the field of tissue engineering because of the favorable biological properties for scaffolding material. However, little is known about the effects of an acellular AM matrix on the osteogenic differentiation of mesenchymal stem cells. In this study, it was found that both basement membrane side and collagenous stroma side of the acellular AM matrix were capable of providing a preferential environment for driving the osteogenic differentiation of human dental apical papilla cells (APCs) with proven stem cell characteristics. Acellular AM matrix potentiated the induction effect of osteogenic supplements (OS) such as ascorbic acid, β-glycerophosphate, and dexamethasone and enhanced the osteogenic differentiation of APCs, as seen by increased core-binding factor alpha 1 (Cbfa-1) phosphorylation, alkaline phosphatase activity, mRNA expression of osteogenic marker genes, and mineralized matrix deposition. Even in the absence of soluble OS, acellular AM matrix also could exert the substrate-induced effect on initiating APCs' differentiation. Especially, the collagenous stroma side was more effective than the basement membrane side. Moreover, the AM-induced effect was significantly inhibited by U0126, an inhibitor of extracellular signaling-regulated kinase 1/2 (ERK1/2) signaling. Taken together, the osteogenic differentiation promoting effect on APCs is AM-specific, which provides potential applications of acellular AM matrix in bone/tooth tissue engineering.

摘要

羊膜(AM)由于其作为支架材料的良好的生物学特性,已在组织工程领域得到广泛应用。然而,关于无细胞 AM 基质对间充质干细胞成骨分化的影响知之甚少。在这项研究中,发现无细胞 AM 基质的基膜侧和胶原质基质侧都能够为具有证明的干细胞特性的人牙髓根尖乳头细胞(APCs)的成骨分化提供有利的环境。无细胞 AM 基质增强了成骨补充剂(OS)如抗坏血酸、β-甘油磷酸和地塞米松的诱导作用,并增强了 APCs 的成骨分化,表现为核心结合因子α 1(Cbfa-1)磷酸化、碱性磷酸酶活性、成骨标记基因的 mRNA 表达和矿化基质沉积增加。即使在没有可溶性 OS 的情况下,无细胞 AM 基质也可以对启动 APCs 的分化产生底物诱导作用。特别是,胶原质基质侧比基膜侧更有效。此外,AM 诱导的作用被细胞外信号调节激酶 1/2(ERK1/2)信号通路抑制剂 U0126 显著抑制。综上所述,对 APCs 的成骨分化促进作用是 AM 特异性的,这为无细胞 AM 基质在骨/牙组织工程中的潜在应用提供了依据。

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