Negative feedback between PTH1R and IGF1 through the Hedgehog pathway in mediating craniofacial bone remodeling

被引：0
作者：
Fan, Yi
Lyu, Ping [1 ,2 ]
Wang, Jiahe [1 ,2 ,3 ]
Wei, Yali [1 ,2 ]
Li, Zucen [1 ,2 ]
Zhang, Shiwen [1 ,4 ]
Ouchi, Takehito [5 ]
Jing, Junjun [1 ]
Yuan, Quan [1 ,4 ]
Rosen, Clifford J. [1 ,6 ]
Zhou, Chenchen [1 ,3 ]
机构：
[1] Sichuan Univ, West China Hosp Stomatol, Natl Ctr Stomatol, Natl Clin Res Ctr Oral Implantol,State Key Lab Ora, Chengdu, Peoples R China
[2] Sichuan Univ, West China Hosp Stomatol, Dept Cariol & Endodont, Chengdu, Peoples R China
[3] Sichuan Univ, West China Hosp Stomatol, Dept Pediat Dent, Chengdu, Peoples R China
[4] Sichuan Univ, West China Hosp Stomatol, Dept Oral Implantol, Chengdu, Peoples R China
[5] Tokyo Dent Coll, Dept Physiol, Tokyo, Japan
[6] Maine Med Ctr Res Inst, Scarborough, ME USA
来源：
JCI INSIGHT | 2025年 / 10卷 / 03期
基金：
中国国家自然科学基金;
关键词：
GROWTH-FACTOR-I; PARATHYROID-HORMONE; PRIMARY FAILURE; STEM-CELLS; RECEPTOR; MICE; TOOTH; MUTATIONS; PROTEIN; GENE;
D O I：
10.1172/jci.insight.183684
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Regeneration of orofacial bone defects caused by inflammation-related diseases or trauma remains an unmet challenge. Parathyroid hormone 1 receptor (PTH1R) signaling is a key mediator of bone remodeling whereas the regulatory mechanisms of PTH1R signaling in oral bone under homeostatic or inflammatory conditions have not been demonstrated by direct genetic evidence. Here, we observed that deletion of PTH1R in Gli1+ progenitors led to increased osteogenesis and osteoclastogenesis. Single-cell and bulk RNA-Seq analysis revealed that PTH1R suppressed the osteogenic potential of Gli1+ progenitors during inflammation. Moreover, we identified upregulated IGF1 expression upon PTH1R deletion. Dual deletion of IGF1 and PTH1R ameliorated the bone- remodeling phenotypes in PTH1R-deficient mice. Furthermore, in vivo evidence revealed an inverse relationship between PTH1R and Hedgehog signaling, which was responsible for the upregulated IGF1 production. Ourwork underscored the negative feedback between PTH1R and IGF1 in craniofacial bone turnover and revealed mechanisms modulating orofacial bone remodeling.
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页数：21
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