Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation

Yuanyuan Yu (), Luyao Wang, Shuaijian Ni, Dijie Li, Jin Liu, Hang Yin Chu, Ning Zhang, Meiheng Sun, Nanxi Li, Qing Ren, Zhenjian Zhuo, Chuanxin Zhong, Duoli Xie, Yongshu Li, Zong-Kang Zhang, Huarui Zhang, Mei Li, Zhenlin Zhang, Lin Chen, Xiaohua Pan, Weibo Xia, Shu Zhang, Aiping Lu (), Bao-Ting Zhang () and Ge Zhang ()
Additional contact information
Yuanyuan Yu: Hong Kong Baptist University
Luyao Wang: Hong Kong Baptist University
Shuaijian Ni: Hong Kong Baptist University
Dijie Li: Hong Kong Baptist University
Jin Liu: Hong Kong Baptist University
Hang Yin Chu: Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery (HKAP)
Ning Zhang: Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery (HKAP)
Meiheng Sun: Hong Kong Baptist University
Nanxi Li: Hong Kong Baptist University
Qing Ren: Hong Kong Baptist University
Zhenjian Zhuo: Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery (HKAP)
Chuanxin Zhong: Hong Kong Baptist University
Duoli Xie: Hong Kong Baptist University
Yongshu Li: Hong Kong Baptist University
Zong-Kang Zhang: Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery (HKAP)
Huarui Zhang: Hong Kong Baptist University
Mei Li: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Zhenlin Zhang: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Lin Chen: Army Medical University
Xiaohua Pan: The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District)
Weibo Xia: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Shu Zhang: Air Force Medical University
Aiping Lu: Hong Kong Baptist University
Bao-Ting Zhang: Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery (HKAP)
Ge Zhang: Hong Kong Baptist University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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’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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-31997-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31997-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-31997-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().