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

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Yu Yuanyuan[1,2,3,4] * ; Wang Luyao[1,2,3,4] * ; Ni Shuaijian[1,2,3,4] * ; Li Dijie[1,2,3,4] ; Liu Jin[1,2,3,4] ; Chu Hang Yin[2,5] ; Zhang Ning[2,5] ; Sun Meiheng[1,2,3,4] ; Li Nanxi[1,2,3,4] ; Ren Qing[1,2,3,4] ; Zhuo Zhenjian[2,5] ; Zhong Chuanxin[1,2,3,4,6] ; Xie Duoli[1,2,3,4] ; Li Yongshu[1,2,3,4] ; Zhang Zong-Kang[2,5] ; Zhang Huarui[1,2,3,4] ; Li Mei[7] ; Zhang Zhenlin[8] ; Chen Lin[9] ; Pan Xiaohua[10] ; Xia Weibo[7] ; Zhang Shu[11] ; Lu Aiping[1,2,3,4] ; Zhang Bao-Ting[2,5] ; Zhang Ge[1,2,3,4] ;
机构： [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 SAR, China. [2]Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery (HKAP), Hong Kong SAR, China. [3]Institute of Precision Medicine and Innovative Drug Discovery (PMID), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [4]Institute of Integrated Bioinformedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [5]School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. [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.
出处：
DOI： 10.1038/s41467-022-31997-8
ISSN：

摘要：
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.© 2022. The Author(s).

基金：
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.).
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外文
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出版当年[2021]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
最新[2025]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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出版当年[2020]版：
Q1 MULTIDISCIPLINARY SCIENCES
最新[2023]版：
Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [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 SAR, China. [2]Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery (HKAP), Hong Kong SAR, China. [3]Institute of Precision Medicine and Innovative Drug Discovery (PMID), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [4]Institute of Integrated Bioinformedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
共同第一作者：
通讯作者：
通讯机构： [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 SAR, China. [2]Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery (HKAP), Hong Kong SAR, China. [3]Institute of Precision Medicine and Innovative Drug Discovery (PMID), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [4]Institute of Integrated Bioinformedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [5]School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
推荐引用方式(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):doi:10.1038/s41467-022-31997-8.
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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