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Strontium attenuates rhBMP-2-induced osteogenic differentiation via formation of Sr-rhBMP-2 complex and suppression of Smad-dependent signaling pathway
Zhang, WJ; Tian, Y; He, HY; Chen, R; Ma, YF; Guo, H; Yuan, Y; Liu, CS; Liu, CS (reprint author), E China Univ Sci & Technol, Minist Educ, Engn Res Ctr Biomed Mat, Shanghai 200237, Peoples R China.; Liu, CS (reprint author), E China Univ Sci & Technol, Minist Educ, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China.
2016
Source PublicationACTA BIOMATERIALIA
ISSN1742-7061
Volume33Issue:-Pages:290—300
Subtype期刊文献
AbstractStrontium (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.
KeywordBone Morphogenetic Protein-2 Bmp Receptor Ia Osteoblast Differentiation Crystal-structure Nuclear-factor Silk Fibroin In-vitro Ranelate Recognition Cells
DOI10.1016/j.actbio.2016.01.042
Indexed BySCI
Language英语
WOS IDWOS:000372688700029
Citation statistics
Document Type期刊论文
Identifierhttp://ir.sinap.ac.cn/handle/331007/25838
Collection中科院上海应用物理研究所2011-2018年
Corresponding AuthorYuan, Y; Liu, CS (reprint author), E China Univ Sci & Technol, Minist Educ, Engn Res Ctr Biomed Mat, Shanghai 200237, Peoples R China.; Liu, CS (reprint author), E China Univ Sci & Technol, Minist Educ, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China.
Recommended Citation
GB/T 7714
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,2016,33(-):290—300.
APA Zhang, WJ.,Tian, Y.,He, HY.,Chen, R.,Ma, YF.,...&Liu, CS .(2016).Strontium attenuates rhBMP-2-induced osteogenic differentiation via formation of Sr-rhBMP-2 complex and suppression of Smad-dependent signaling pathway.ACTA BIOMATERIALIA,33(-),290—300.
MLA Zhang, WJ,et al."Strontium attenuates rhBMP-2-induced osteogenic differentiation via formation of Sr-rhBMP-2 complex and suppression of Smad-dependent signaling pathway".ACTA BIOMATERIALIA 33.-(2016):290—300.
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