文献类型：期刊文献

英文题名：Attenuating osteoarthritis by a high efficient anti-bone resorption injectable pH-responsive bisphosphonate-conjugated nano-apatite system

作者：Geng, Zhen[1,3];Wang, Xiaogang[1,3];Yu, Yuanman[1,3];Ji, Luli[1,3];Wang, Jing[1,2];Liu, Changsheng[1,3,4]

机构：[1]East China Univ Sci & Technol, Minist Educ, Key Lab Ultrafine Mat, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Minist Educ, Engn Res Ctr Biomed Mat, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Frontiers Sci Ctr Mat & Dynam Chem, Shanghai 200237, Peoples R China

年份：2021

卷号：420

外文期刊名：CHEMICAL ENGINEERING JOURNAL

收录：;EI(收录号：20204709522486);WOS:【SCI-EXPANDED(收录号:WOS:000664736100002)】；

基金：Acknowledgements This work was financially supported by the National Natural Science Foundation of China for Innovative Research Groups (Grant No. 51621002) , and China Postdoctoral Science Foundation (Grant No. 2018M640350) .

语种：英文

外文关键词：Osteoarthritis; Subchondral bone remodeling; Osteoclastic activity; Bisphosphonate-conjugated nano-apatite; pH-responsive

摘要：Osteoarthritis (OA) has become one of the most prevalent and costly diseases worldwide. Previous studies have confirmed that subchondral bone abnormal remodeling caused by overactive osteoclast bone resorption was the major cause of OA. In this study, we fabricated a bisphosphonate-conjugated nano-apatite (NP-BP) system via hydrothermal method and in-situ adsorption process. The NP-BP showed sustainable and pH-responsive release behavior of bisphosphonate. The in vitro experiment revealed that NP-BP could effectively inhibit osteoclast differentiation and suppress osteoclast bone resorption through down regulating the expressions of osteoclastic related genes, including TRAP, OSCAR, NFATc1, and Cathepsin K. The in vivo study in an OA rat model indicated that the NP-BP could relieve joint pain, attenuate articular cartilage degeneration, and lower histologic OARSI score. In parallel, the micro-CT analysis, including total tissue volume (TV), subchondral bone plate thickness (SBP Th.), and trabecular pattern factor (Tb. Pf), showed that the NP-BP could efficiently inhibit subchondral bone abnormal remodeling. In addition, the immunostaining analyses and the micro-CT based angiography demonstrated that the NP-BP suppressed the expressions of Collagen X, RANKL, Osterix, and CD31 and inhibited aberrant angiogenesis. Moreover, the NP-BP inhibited the intrusion of subchondral bone into calcified cartilage. As a result, the developed pH-responsive NP-BP system, which showed high efficiency in inhibiting osteoclastic bone resorption and subchondral bone abnormal remodeling, has potential applications for early OA treatment.