文献类型：期刊文献

英文题名：Calcium ion-induced formation of β-sheet/-turn structure leading to alteration of osteogenic activity of bone morphogenetic protein-2

作者：Zhang, Wenjing[1,2];He, Hongyan[3];Tian, Yu[1,2];Gan, Qi[2,3];Zhang, Jing[3];Yuan, Yuan[1,3];Liu, Changsheng[1,2,3]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China;[3]E China Univ Sci & Technol, Engn Res Ctr Biomed Mat, Minist Educ, Shanghai 200237, Peoples R China

年份：2015

卷号：5

外文期刊名：SCIENTIFIC REPORTS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000358545700001)】；

基金：This work was supported by grants from the National Basic Research Program of China (973 Program, No. 2012CB933600), the 111 Project (B14018), the National Natural Science Foundation of China (No. 31100679, 31330028 and 31470924), the Program for New Century Excellent Talents in University (No. NCET-11-0640), and the National Special Fund for the State Key Laboratory of Bioreactor Engineering (No. 2060204).

语种：英文

摘要：Preserving bioactivity of bone morphogenetic protein 2 (BMP-2) still remains a challenge in protein-based therapy. It is not known how Ca2+ released from extracellular matrix or existing in physiological environment influences bioactivity in situ till now. Here, effects of extracellular Ca2+ on conformation and osteogenic bioactivity of recombinant human BMP-2 (rhBMP-2) were investigated systematically. In vitro results indicated that Ca2+ could bind rhBMP-2 rapidly and had no obvious effect on cell behaviors. Low concentration of Ca2+ (0.18 mM) enhanced rhBMP-2-induced osteogenic differentiation, while high Ca2+ concentration (>1.80 mM) exerted negative effect. In vivo ectopic bone formation exhibited similar trend. Further studies by circular dichroism spectroscopy, fluorescence spectroscopy, together with cell culture experiments revealed at low concentration, weak interaction of Ca2+ and rhBMP-2 slightly increased beta-sheet/-turn content and facilitated recognition of BMP-2 and BMPRIA. But, high Ca2+ concentration (>1.8 mM) induced formation of CarhBMP-2 complex and markedly increased content of beta-sheet/-turn, which led to inhibition binding of rhBMP-2 and BMPRIA and thus suppression of downstream Smad1/5/8, ERK1/2 and p38 mitogen-associated protein kinase signaling pathways. Our work suggests osteogenic bioactivity of BMP-2 can be adjusted via extracellular Ca2+, which should provide guide and assist for development of BMP-2-based materials for bone regeneration.