Cargando…

Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis

Whether sensory nerve can sense bone density or metabolic activity to control bone homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor 4 (EP4) in sensory nerves to regulate bone formation by inhibiting sympathetic activity through the...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Hao, Hu, Bo, Lv, Xiao, Zhu, Shouan, Zhen, Gehua, Wan, Mei, Jain, Amit, Gao, Bo, Chai, Yu, Yang, Mi, Wang, Xiao, Deng, Ruoxian, Wang, Lei, Cao, Yong, Ni, Shuangfei, Liu, Shen, Yuan, Wen, Chen, Huajiang, Dong, Xinzhong, Guan, Yun, Yang, Huilin, Cao, Xu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331599/
https://www.ncbi.nlm.nih.gov/pubmed/30643142
http://dx.doi.org/10.1038/s41467-018-08097-7
_version_ 1783387165851385856
author Chen, Hao
Hu, Bo
Lv, Xiao
Zhu, Shouan
Zhen, Gehua
Wan, Mei
Jain, Amit
Gao, Bo
Chai, Yu
Yang, Mi
Wang, Xiao
Deng, Ruoxian
Wang, Lei
Cao, Yong
Ni, Shuangfei
Liu, Shen
Yuan, Wen
Chen, Huajiang
Dong, Xinzhong
Guan, Yun
Yang, Huilin
Cao, Xu
author_facet Chen, Hao
Hu, Bo
Lv, Xiao
Zhu, Shouan
Zhen, Gehua
Wan, Mei
Jain, Amit
Gao, Bo
Chai, Yu
Yang, Mi
Wang, Xiao
Deng, Ruoxian
Wang, Lei
Cao, Yong
Ni, Shuangfei
Liu, Shen
Yuan, Wen
Chen, Huajiang
Dong, Xinzhong
Guan, Yun
Yang, Huilin
Cao, Xu
author_sort Chen, Hao
collection PubMed
description Whether sensory nerve can sense bone density or metabolic activity to control bone homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor 4 (EP4) in sensory nerves to regulate bone formation by inhibiting sympathetic activity through the central nervous system. PGE2 secreted by osteoblasts increases when bone density decreases as demonstrated in osteoporotic animal models. Ablation of sensory nerves erodes the skeletal integrity. Specifically, knockout of the EP4 gene in the sensory nerves or cyclooxygenase-2 (COX2) in the osteoblastic cells significantly reduces bone volume in adult mice. Sympathetic tone is increased in sensory denervation models, and propranolol, a β2-adrenergic antagonist, rescues bone loss. Furthermore, injection of SW033291, a small molecule to increase PGE2 level locally, significantly boostes bone formation, whereas the effect is obstructed in EP4 knockout mice. Thus, we show that PGE2 mediates sensory nerve to control bone homeostasis and promote regeneration.
format Online
Article
Text
id pubmed-6331599
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-63315992019-01-16 Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis Chen, Hao Hu, Bo Lv, Xiao Zhu, Shouan Zhen, Gehua Wan, Mei Jain, Amit Gao, Bo Chai, Yu Yang, Mi Wang, Xiao Deng, Ruoxian Wang, Lei Cao, Yong Ni, Shuangfei Liu, Shen Yuan, Wen Chen, Huajiang Dong, Xinzhong Guan, Yun Yang, Huilin Cao, Xu Nat Commun Article Whether sensory nerve can sense bone density or metabolic activity to control bone homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor 4 (EP4) in sensory nerves to regulate bone formation by inhibiting sympathetic activity through the central nervous system. PGE2 secreted by osteoblasts increases when bone density decreases as demonstrated in osteoporotic animal models. Ablation of sensory nerves erodes the skeletal integrity. Specifically, knockout of the EP4 gene in the sensory nerves or cyclooxygenase-2 (COX2) in the osteoblastic cells significantly reduces bone volume in adult mice. Sympathetic tone is increased in sensory denervation models, and propranolol, a β2-adrenergic antagonist, rescues bone loss. Furthermore, injection of SW033291, a small molecule to increase PGE2 level locally, significantly boostes bone formation, whereas the effect is obstructed in EP4 knockout mice. Thus, we show that PGE2 mediates sensory nerve to control bone homeostasis and promote regeneration. Nature Publishing Group UK 2019-01-14 /pmc/articles/PMC6331599/ /pubmed/30643142 http://dx.doi.org/10.1038/s41467-018-08097-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chen, Hao
Hu, Bo
Lv, Xiao
Zhu, Shouan
Zhen, Gehua
Wan, Mei
Jain, Amit
Gao, Bo
Chai, Yu
Yang, Mi
Wang, Xiao
Deng, Ruoxian
Wang, Lei
Cao, Yong
Ni, Shuangfei
Liu, Shen
Yuan, Wen
Chen, Huajiang
Dong, Xinzhong
Guan, Yun
Yang, Huilin
Cao, Xu
Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis
title Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis
title_full Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis
title_fullStr Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis
title_full_unstemmed Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis
title_short Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis
title_sort prostaglandin e2 mediates sensory nerve regulation of bone homeostasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331599/
https://www.ncbi.nlm.nih.gov/pubmed/30643142
http://dx.doi.org/10.1038/s41467-018-08097-7
work_keys_str_mv AT chenhao prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT hubo prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT lvxiao prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT zhushouan prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT zhengehua prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT wanmei prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT jainamit prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT gaobo prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT chaiyu prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT yangmi prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT wangxiao prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT dengruoxian prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT wanglei prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT caoyong prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT nishuangfei prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT liushen prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT yuanwen prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT chenhuajiang prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT dongxinzhong prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT guanyun prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT yanghuilin prostaglandine2mediatessensorynerveregulationofbonehomeostasis
AT caoxu prostaglandine2mediatessensorynerveregulationofbonehomeostasis