中文版 | English
Title

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

Author
Corresponding AuthorYu,Yuanyuan; Lu,Aiping; Zhang,Ge
Publication Years
2022-07-22
DOI
Source Title
EISSN
2041-1723
Volume13Issue:1
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 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.","Antibodies targeting sclerostin can ameliorate postmenopausal osteoporosis but present some cardiovascular risk. Here the authors show that the cardiovascular and skeletal effects of sclerostin are mediated by different loops, suggesting ways to preserve the positive effects on bone formation while avoiding the negative cardiovascular consequences."]
URL[Source Record]
Indexed By
Language
English
Important Publications
NI Journal Papers
SUSTech Authorship
Others
Funding Project
National Key R&D Program from the Ministry of Science and Technology of China[2018YFA0800800] ; Hong Kong General Research Fund from the Research Grants Council of the Hong Kong Special Administrative Region, China["12102120","12114416","12100921","12103519","12136616","14103420","14103121","14109721"] ; Theme-based Research Scheme from the Research Grants Council of the Hong Kong Special Administrative Region, China[T12-201/20-R] ; Basic and Applied Basic Research Fund from Department of Science and Technology of Guangdong Province[2019B1515120089] ; Inter-institutional Collaborative Research Scheme from Hong Kong Baptist University[RC-ICRS/19-20/01] ; University-Industry Collaboration Programme from Innovation and Technology Commissions of the Hong Kong Special Administrative Region, China["UIM/328","UIM/298"]
WOS Research Area
Science & Technology - Other Topics
WOS Subject
Multidisciplinary Sciences
WOS Accession No
WOS:000829110700004
Publisher
Scopus EID
2-s2.0-85134618575
Data Source
Web of Science
Citation statistics
Cited Times [WOS]:29
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/359506
DepartmentDepartment of Materials Science and Engineering
Affiliation
1.Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ),School of Chinese Medicine,Hong Kong Baptist University,Hong Kong
2.Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery (HKAP),Hong Kong
3.Institute of Precision Medicine and Innovative Drug Discovery (PMID),School of Chinese Medicine,Hong Kong Baptist University,Hong Kong
4.Institute of Integrated Bioinformedicine and Translational Science (IBTS),School of Chinese Medicine,Hong Kong Baptist University,Hong Kong
5.School of Chinese Medicine,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong
6.Department of Materials Science and Engineering,Southern University of Science and Technology,Shenzhen,China
7.Department of Endocrinology,National Health Commission Key Laboratory of Endocrinology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China
8.Shanghai Clinical Research Center of Bone Disease,Department of Osteoporosis and Bone Disease,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai,China
9.Department of Wound Repair and Rehabilitation Medicine,State Key Laboratory of Trauma,Burns and Combined Injury,Trauma Center,Research Institute of Surgery,Daping Hospital,Army Medical University,Chongqing,China
10.Orthopedic Center,The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District),Shenzhen,China
11.The Key Laboratory of Aerospace Medicine,Ministry of Education,Air Force Medical University,Xi’an,Shaanxi,China
Recommended Citation
GB/T 7714
Yu,Yuanyuan,Wang,Luyao,Ni,Shuaijian,et al. Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation[J]. NATURE COMMUNICATIONS,2022,13(1).
APA
Yu,Yuanyuan.,Wang,Luyao.,Ni,Shuaijian.,Li,Dijie.,Liu,Jin.,...&Zhang,Ge.(2022).Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation.NATURE COMMUNICATIONS,13(1).
MLA
Yu,Yuanyuan,et al."Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation".NATURE COMMUNICATIONS 13.1(2022).
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