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题名:
Strontium attenuates rhBMP-2-induced osteogenic differentiation via formation of Sr-rhBMP-2 complex and suppression of Smad-dependent signaling pathway
作者: Zhang, WJ; Tian, Y; He, HY; Chen, R; Ma, YF; Guo, H; Yuan, Y; Liu, CS
刊名: ACTA BIOMATERIALIA
出版日期: 2016
卷号: 33, 期号:-, 页码:290—300
关键词: BONE MORPHOGENETIC PROTEIN-2 ; BMP RECEPTOR IA ; OSTEOBLAST DIFFERENTIATION ; CRYSTAL-STRUCTURE ; NUCLEAR-FACTOR ; SILK FIBROIN ; IN-VITRO ; RANELATE ; RECOGNITION ; CELLS
DOI: 10.1016/j.actbio.2016.01.042
通讯作者: Yuan, Y ; Liu, CS (reprint author), E China Univ Sci & Technol, Minist Educ, Engn Res Ctr Biomed Mat, Shanghai 200237, Peoples R China. ; Yuan, Y ; Liu, CS (reprint author), E China Univ Sci & Technol, Minist Educ, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China.
文章类型: 期刊文献
英文摘要: Strontium (Sr2+) has pronounced effects on stimulating bone formation and inhibiting bone resorption in bone regeneration. In this current study, the effect and the underlying mechanism involved of Sr2+ on the biological activity of bone morphogenetic protein-2 (BMP-2) were studied in detail with pluripotent skeletal muscle myogenic progenitor C2C12 model cell line. The results indicated that Sr2+ could bind recombinant human BMP-2 (rhBMP-2) rapidly, even in the presence of Ca2+ and Mg2+, and inhibited rhBMP-2-induced osteogenic differentiation in vitro and osteogenetic efficiency in vivo. Further studies demonstrated that Sr2+ treatment undermined the binding capacity of rhBMP-2 with its receptor BMPRIA and thus attenuated Smad 1/5/8 phosphorylation without affecting their dephosphorylation in C2C12 cells. Furthermore, circular dichroism spectroscopy, fluorescence spectroscopy and X-ray photoelectron spectroscopy all revealed that the inhibitory effect of Sr2+ on the rhBMP-2 osteogenic activity was associated with the formation of Sr-rhBMP-2 complex and ensuing enhancement of (3-sheet structure. Our work suggests the activity of rhBMP-2 to induce osteogenic differentiation was decreased by directly interaction with free Sr ions in solution, which should provide guide and assist for development of BMP-2-based materials for bone regeneration. Statement of Significance Due to easy denaturation and ensuing the reduced activity of rhBMP-2, preserving/enhancing the capacity of rhBMP-2 to induce osteogenic differentiation is of critical importance in developing the protein based therapy. Cations as effective elements influence the conformation and thereby the bioactivity of protein. Strontium (Sr2+), stimulating bone formation and inhibiting bone resorption, has been incorporated into biomaterials/scaffold to improve the bioactivity for bone-regeneration applications. However, Sr2+-induced changes in the conformation and bioactivity of BMP-2 have never been investigated. In this study, the formation of Sr-rhBMP-2 complex inhibited the osteogenic differentiation in vitro and osteogenetic efficiency in vivo through the inhibition of BMP/Smad signaling pathway, providing guidance for development of Sr-containing BMP-2-based bone scaffold/matrice and other Sr-dopped protein therapy. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
收录类别: SCI
语种: 英语
WOS记录号: WOS:000372688700029
ISSN号: 1742-7061
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.sinap.ac.cn/handle/331007/25838
Appears in Collections:中科院上海应用物理研究所2011-2017年_期刊论文

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Recommended Citation:
Zhang, WJ,Tian, Y,He, HY,et al. Strontium attenuates rhBMP-2-induced osteogenic differentiation via formation of Sr-rhBMP-2 complex and suppression of Smad-dependent signaling pathway[J]. ACTA BIOMATERIALIA,2016-01-01,33(-):290—300.
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