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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) ofLRP5 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), andβ‍-catenin (P<0.05). For the in vivo experiment, the SP7 overexpression virus was injected into a bone defect model ofLRP5 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 inLRP5 cKO mice. Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.

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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