转录因子SP7改善低密度脂蛋白受体相关蛋白5（LRP5）条件性缺失小鼠的骨缺损愈合

Yue XI; Qifeng JIANG; Wei DAI; Chaozhen CHEN; Yang WANG; Xiaoyan MIAO; Kaichen LAI; Zhiwei JIANG; Guoli YANG; Ying WANG

doi:10.1631/jzus.B2300531

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转录因子SP7改善低密度脂蛋白受体相关蛋白5（LRP5）条件性缺失小鼠的骨缺损愈合

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Research Article | Updated：2025-03-13

转录因子SP7改善低密度脂蛋白受体相关蛋白5（LRP5）条件性缺失小鼠的骨缺损愈合
SP7 transcription factor ameliorates bone defect healing in low-density lipoprotein receptor-related protein 5 (LRP5)-dependent osteoporosis mice—席月¹，蒋奇锋²，戴薇¹，陈朝真¹ ，王洋¹，缪晓燕¹，赖恺晨¹，姜治伟¹，杨国利¹，王莹¹
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2025年26卷第3期页码：254-268
Affiliations：

1.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
2.School of Stomatology, Zhejiang University, Hangzhou 310058, China
Funds：

浙江大学医学院附属口腔医院，浙江大学口腔医学院，浙江省口腔疾病临床医学研究中心，浙江省口腔生物医学研究重点实验室，浙江大学癌症研究院，口腔生物材料与器械浙江省工程研究中心, 中国杭州市(310000)
DOI：10.1631/jzus.B2300531
中图分类号：
CSTR：
收稿日期：2023-08-01，

修回日期：2023-11-30，

网络出版日期：2025-03-01，

纸质出版日期：2025-03-13
Accepted：

.转录因子SP7改善低密度脂蛋白受体相关蛋白5（LRP5）条件性缺失小鼠的骨缺损愈合[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(03):254-268.

Yue XI, Qifeng JIANG, Wei DAI, et al. SP7 transcription factor ameliorates bone defect healing in low-density lipoprotein receptor-related protein 5 (LRP5)-dependent osteoporosis mice—席月¹，蒋奇锋²，戴薇¹，陈朝真¹ ，王洋¹，缪晓燕¹，赖恺晨¹，姜治伟¹，杨国利¹，王莹¹[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(3): 254-268.
.转录因子SP7改善低密度脂蛋白受体相关蛋白5（LRP5）条件性缺失小鼠的骨缺损愈合[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(03):254-268. DOI： 10.1631/jzus.B2300531.

Yue XI, Qifeng JIANG, Wei DAI, et al. SP7 transcription factor ameliorates bone defect healing in low-density lipoprotein receptor-related protein 5 (LRP5)-dependent osteoporosis mice—席月¹，蒋奇锋²，戴薇¹，陈朝真¹ ，王洋¹，缪晓燕¹，赖恺晨¹，姜治伟¹，杨国利¹，王莹¹[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(3): 254-268. DOI： 10.1631/jzus.B2300531.

摘要

低密度脂蛋白受体相关蛋白5（LRP5）的功能丧失突变将导致骨形成减少，从而最终导致低骨量的表型。先前研究报道了LRP5启动子存在转录因子SP7的结合位点。此外，SP7在种植体骨整合过程中具有上调LRP5表达的关键作用。但SP7在改善LRP5缺失所致骨质疏松的作用机制尚不明确。本研究使用成骨细胞LRP5条件性缺失小鼠展开相关研究，该小鼠具有骨质疏松表型。细胞实验结果表明，SP7可促进LRP5表达并上调包括碱性磷酸酶（

ALP

）、Runt相关转录因子2（

Runx2

）和β-catenin等成骨相关基因的表达（

0.05）。体内实验将SP7过表达慢病毒注射到LRP5条件性敲除小鼠骨缺损区域，愈合4周后，与对照组相比，SP7治疗组骨密度（BMD）（

0.001）和骨体积分数（BV/TV）（

0.001）显著升高，而骨小梁分离系数（Tb.Sp）显著减小（

0.05）。上述数据表明，SP7可改善LRP5条件性缺失所致小鼠骨质疏松的骨缺损愈合过程。该研究为改善LRP5缺失所致骨质疏松提供了潜在治疗策略。

Abstract

Loss-of-function variants of low-density lipoprotein receptor-related protein 5 (LRP5) can lead to reduced bone formation

culminating in diminished bone mass. Our previous study reported transcription factor osterix (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

(

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) (

0.001) and volumetric density (bone volume (BV)/total volume (TV)) (

0.001)

and decreased trabecular separation (Tb.‍Sp) (

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.

关键词

Keywords

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