@article{d08d64c7937042298410cf4572e76f25,
title = "Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation",
abstract = "Sclerostin negatively regulates bone formation by antagonizing Wnt signalling. An antibody targeting sclerostin for the treatment of postmenopausal osteoporosis was approved by the U.S. Food and Drug Administration, with a boxed warning for cardiovascular risk. Here we demonstrate that sclerostin participates in protecting cardiovascular system and inhibiting bone formation via different loops. Loop3 deficiency by genetic truncation could maintain sclerostin{\textquoteright}s protective effect on the cardiovascular system while attenuating its inhibitory effect on bone formation. We identify an aptamer, named aptscl56, which specifically targets sclerostin loop3 and use a modified aptscl56 version, called Apc001PE, as specific in vivo pharmacologic tool to validate the above effect of loop3. Apc001PE has no effect on aortic aneurysm and atherosclerotic development in ApoE−/− mice and hSOSTki.ApoE−/− mice with angiotensin II infusion. Apc001PE can promote bone formation in hSOSTki mice and ovariectomy-induced osteoporotic rats. In summary, sclerostin loop3 cannot participate in protecting the cardiovascular system, but participates in inhibiting bone formation.",
author = "Yuanyuan Yu and Luyao Wang and Shuaijian Ni and Dijie Li and Jin Liu and Chu, {Hang Yin} and Ning Zhang and Meiheng Sun and Nanxi Li and Qing Ren and Zhenjian Zhuo and Chuanxin Zhong and Duoli Xie and Yongshu Li and Zhang, {Zong Kang} and Huarui Zhang and Mei Li and Zhenlin Zhang and Lin Chen and Xiaohua Pan and Weibo Xia and Shu Zhang and Aiping Lu and Zhang, {Bao Ting} and Ge Zhang",
note = "Funding Information: This study was supported by the National Key R&D Program from the Ministry of Science and Technology of China (Project No. 2018YFA0800800, G.Z.), Hong Kong General Research Fund from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. 12102120, Y.Y.; Project No. 12114416, G.Z.; Project No. 12100921, G.Z.; Project No. 12103519, J.L.; Project No. 12136616, J.L.; Project No. 14103420, Z.K.Z.; Project No. 14103121, Z.K.Z. and Project No. 14109721, B.T.Z.), Theme-based Research Scheme from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. T12-201/20-R, A.L.), Basic and Applied Basic Research Fund from Department of Science and Technology of Guangdong Province (Project No. 2019B1515120089, G.Z.), Inter-institutional Collaborative Research Scheme from Hong Kong Baptist University (Project No. RC-ICRS/19-20/01, G.Z.), University-Industry Collaboration Programme from Innovation and Technology Commissions of the Hong Kong Special Administrative Region, China (Project No. UIM/298, G.Z.) and University-Industry Collaboration Programme from Innovation and Technology Commissions of the Hong Kong Special Administrative Region, China (Project No. UIM/328, B.T.Z.). Publisher Copyright: {\textcopyright} The Author(s) 2022",
year = "2022",
month = jul,
day = "22",
doi = "10.1038/s41467-022-31997-8",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}