SP7 transcription factor ameliorates bone defect healing in low-density lipoprotein receptor-related protein 5 (LRP5)-dependent osteoporosis mice.

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

Return

SP7 transcription factor ameliorates bone defect healing in low-density lipoprotein receptor-related protein 5 (LRP5)-dependent osteoporosis mice.

Author: Yue XI ¹ ; Qifeng JIANG ² ; Wei DAI ¹ ; Chaozhen CHEN ¹ ; Yang WANG ¹ ; Xiaoyan MIAO ¹ ; Kaichen LAI ¹ ; Zhiwei JIANG ¹ ; Guoli YANG ³ ; Ying WANG ⁴
Author Information

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.
3. 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. guo_li1214@zju.edu.cn.
4. 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. guo_li1214@zju.edu.cn, 7314032@zju.edu.cn.
Publication Type:Journal Article
Keywords: Defect healing; Gene therapy; Low-density lipoprotein receptor-related protein 5 (LRP5); Osteoporosis; Transcription factor osterix (SP7)
MeSH: Animals; Low Density Lipoprotein Receptor-Related Protein-5/metabolism*; Osteoporosis/genetics*; Mice; Mice, Knockout; Sp7 Transcription Factor/physiology*; Osteogenesis; Bone Density; Osteoblasts/metabolism*; Core Binding Factor Alpha 1 Subunit/metabolism*; Mice, Inbred C57BL; beta Catenin/metabolism*
From: Journal of Zhejiang University. Science. B 2025;26(3):254-268
CountryChina
Language:English
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 (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) and 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.