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On-line Access: 2024-08-27

Received: 2023-10-17

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Journal of Zhejiang University SCIENCE B

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SP7 transcription factor ameliorates bone defect healing in low-density lipoprotein receptor-related protein 5-dependent osteoporosis mice


Author(s):  Yue XI, Qifeng JIANG, Wei DAI, Chaozhen CHEN, Yang WANG, Xiaoyan MIAO, Kaichen LAI, Zhiwei JIANG, Guoli YANG, Ying WANG

Affiliation(s):  Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China; more

Corresponding email(s):  guo_li1214@zju.edu.cn, 7314032@zju.edu.cn

Key Words:  Gene therapy; LRP5; SP7; Osteoporosis; Defect healing


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Yue XI, Qifeng JIANG, Wei DAI, Chaozhen CHEN, Yang WANG, Xiaoyan MIAO, Kaichen LAI, Zhiwei JIANG, Guoli YANG, Ying WANG. SP7 transcription factor ameliorates bone defect healing in low-density lipoprotein receptor-related protein 5-dependent osteoporosis mice[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300531

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journal="Journal of Zhejiang University Science B",
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publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2300531"
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%A Yang WANG
%A Xiaoyan MIAO
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%A Zhiwei JIANG
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doi="https://doi.org/10.1631/jzus.B2300531"

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A1 - Qifeng JIANG
A1 - Wei DAI
A1 - Chaozhen CHEN
A1 - Yang WANG
A1 - Xiaoyan MIAO
A1 - Kaichen LAI
A1 - Zhiwei JIANG
A1 - Guoli YANG
A1 - Ying WANG
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doi="https://doi.org/10.1631/jzus.B2300531"


Abstract: 
Loss-of-function variants in the low-density lipoprotein receptor-related protein 5 (LRP5) can lead to reduced bone formation, culminating in diminished bone mass. Our previous study reported SP7 transcription factor (SP7) binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration. However, the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown. In this study, we used mice with a conditional knockout (cKO) of LRP5 in mature osteoblasts, which presented decreased osteogenesis. The in vitro experimental results showed that SP7 could promote LRP5 expression, thereby upregulating the osteogenic markers such as alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2) and β-catenin (P < 0.05). For the in vivo experiment, the SP7 overexpression virus was injected into a bone defect model of LRP5 cKO mice, resulting in increased bone mineral density (BMD) (P < 0.001), volumetric density (bone volume (BV) / total volume (TV)) (P < 0.001) and decreased trabecular separation (Tb. Sp) (P < 0.05). These data suggested that SP7 could ameliorate bone defect healing in LRP5 cKO mice. Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.

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