Cargando…
Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation
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 pa...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307627/ https://www.ncbi.nlm.nih.gov/pubmed/35869074 http://dx.doi.org/10.1038/s41467-022-31997-8 |
_version_ | 1784752805133680640 |
---|---|
author | Yu, Yuanyuan Wang, Luyao Ni, Shuaijian Li, Dijie Liu, Jin Chu, Hang Yin Zhang, Ning Sun, Meiheng Li, Nanxi Ren, Qing Zhuo, Zhenjian Zhong, Chuanxin Xie, Duoli Li, Yongshu Zhang, Zong-Kang Zhang, Huarui Li, Mei Zhang, Zhenlin Chen, Lin Pan, Xiaohua Xia, Weibo Zhang, Shu Lu, Aiping Zhang, Bao-Ting Zhang, Ge |
author_facet | Yu, Yuanyuan Wang, Luyao Ni, Shuaijian Li, Dijie Liu, Jin Chu, Hang Yin Zhang, Ning Sun, Meiheng Li, Nanxi Ren, Qing Zhuo, Zhenjian Zhong, Chuanxin Xie, Duoli Li, Yongshu Zhang, Zong-Kang Zhang, Huarui Li, Mei Zhang, Zhenlin Chen, Lin Pan, Xiaohua Xia, Weibo Zhang, Shu Lu, Aiping Zhang, Bao-Ting Zhang, Ge |
author_sort | Yu, Yuanyuan |
collection | PubMed |
description | 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’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 hSOST(ki).ApoE(−/−) mice with angiotensin II infusion. Apc001PE can promote bone formation in hSOST(ki) mice and ovariectomy-induced osteoporotic rats. In summary, sclerostin loop3 cannot participate in protecting the cardiovascular system, but participates in inhibiting bone formation. |
format | Online Article Text |
id | pubmed-9307627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93076272022-07-24 Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation Yu, Yuanyuan Wang, Luyao Ni, Shuaijian Li, Dijie Liu, Jin Chu, Hang Yin Zhang, Ning Sun, Meiheng Li, Nanxi Ren, Qing Zhuo, Zhenjian Zhong, Chuanxin Xie, Duoli Li, Yongshu Zhang, Zong-Kang Zhang, Huarui Li, Mei Zhang, Zhenlin Chen, Lin Pan, Xiaohua Xia, Weibo Zhang, Shu Lu, Aiping Zhang, Bao-Ting Zhang, Ge Nat Commun Article 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’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 hSOST(ki).ApoE(−/−) mice with angiotensin II infusion. Apc001PE can promote bone formation in hSOST(ki) mice and ovariectomy-induced osteoporotic rats. In summary, sclerostin loop3 cannot participate in protecting the cardiovascular system, but participates in inhibiting bone formation. Nature Publishing Group UK 2022-07-22 /pmc/articles/PMC9307627/ /pubmed/35869074 http://dx.doi.org/10.1038/s41467-022-31997-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Yu, Yuanyuan Wang, Luyao Ni, Shuaijian Li, Dijie Liu, Jin Chu, Hang Yin Zhang, Ning Sun, Meiheng Li, Nanxi Ren, Qing Zhuo, Zhenjian Zhong, Chuanxin Xie, Duoli Li, Yongshu Zhang, Zong-Kang Zhang, Huarui Li, Mei Zhang, Zhenlin Chen, Lin Pan, Xiaohua Xia, Weibo Zhang, Shu Lu, Aiping Zhang, Bao-Ting Zhang, Ge Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation |
title | Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation |
title_full | Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation |
title_fullStr | Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation |
title_full_unstemmed | Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation |
title_short | Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation |
title_sort | targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307627/ https://www.ncbi.nlm.nih.gov/pubmed/35869074 http://dx.doi.org/10.1038/s41467-022-31997-8 |
work_keys_str_mv | AT yuyuanyuan targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT wangluyao targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT nishuaijian targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT lidijie targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT liujin targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT chuhangyin targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT zhangning targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT sunmeiheng targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT linanxi targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT renqing targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT zhuozhenjian targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT zhongchuanxin targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT xieduoli targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT liyongshu targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT zhangzongkang targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT zhanghuarui targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT limei targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT zhangzhenlin targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT chenlin targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT panxiaohua targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT xiaweibo targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT zhangshu targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT luaiping targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT zhangbaoting targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation AT zhangge targetingloop3ofsclerostinpreservesitscardiovascularprotectiveactionandpromotesboneformation |