文献类型：期刊文献

英文题名：Enhanced bioactivity of bone morphogenetic protein-2 with low dose of 2-N, 6-O-sulfated chitosan in vitro and in vivo

作者：Zhou, Huanjun[1,2]; Qian, Jiangchao[1]; Wang, Jing[2]; Yao, Wantong[3]; Liu, Changsheng[1,2]; Chen, Jianguo[3]; Cao, Xuehua[3]

机构：[1] The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; [2] Key Laboratory for Ultrafine Materials, Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China; [3] Engineering Research Center for Biomedical Materials, Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China

年份：2009

卷号：30

期号：9

起止页码：1715

外文期刊名：Biomaterials

收录：EI(收录号：20090611895441)

语种：英文

外文关键词：Bone - Tissue engineering - Chitosan - Phosphatases - Sulfur compounds

摘要：Bone morphogenetic protein-2 (BMP-2) has been widely used as an effective growth factor in bone tissue engineering. However, large amounts of BMP-2 are required to induce new bone and the resulting side effects limit its clinical application. Sulfated polysaccharides, such as native heparin, and heparan sulfate have been found to modulate BMP-2 bioactivity and play pivotal roles in bone metabolism. Whereas the direct role of chitosan modified with sulfate group in BMP-2 signaling has not been reported till now. In the present study, several sulfated chitosans with different positions were synthesized by regioselective reactions firstly. Using C2C12 myoblast cells as in vitro models, the enhanced bioactivity of BMP-2 was attributed primarily to the stimulation from 6-O-sulfated chitosan (6SCS), while 2-N-sulfate was subsidiary group with less activation. Low dose of 2-N, 6-O-sulfated chitosan (26SCS) showed significant enhancement on the alkaline phosphatase (ALP) activity and the mineralization formation induced by BMP-2, as well as the expression of ALP and osteocalcin mRNA. Moreover, increased chain-length and further sulfation on 26SCS also resulted in a higher ALP activity. Dose-dependent effects on BMP-2 bioactivity were observed in both sulfated chitosan and heparin. Compared with native heparin, 26SCS showed much stronger simultaneous effects on the BMP-2 bioactivity at low dose. Stimulated secreted Noggin protein failed to block the function of BMP-2 in the presence of 26SCS. The BMP-2 ligand bound to its receptor was enhanced by low dose of 26SCS, whereas weakened by the increasing amounts of 26SCS. Furthermore, simultaneous administration of BMP-2 and 26SCS in vivo dose-dependently induced larger amounts of ectopic bone formation compared with BMP-2 alone. These findings clearly indicate that 26SCS is a more potent enhancer for BMP-2 bioactivity to induce osteoblastic differentiation in vitro and in vivo by promoting BMP-2 signaling pathway, suggesting that 26SCS could be used as the synergistic factor of BMP-2 for bone regeneration. ? 2008 Elsevier Ltd. All rights reserved.