Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis

被引：286

作者：

Chen, Hao ^{[1
,2
]}

Hu, Bo ^{[1
,3
]}

Lv, Xiao ^{[1
]}

Zhu, Shouan ^{[1
]}

Zhen, Gehua ^{[1
]}

Wan, Mei ^{[1
]}

Jain, Amit ^{[1
]}

Gao, Bo ^{[1
]}

Chai, Yu ^{[1
]}

Yang, Mi ^{[1
]}

Wang, Xiao ^{[1
]}

Deng, Ruoxian ^{[1
]}

Wang, Lei ^{[1
]}

Cao, Yong ^{[1
]}

Ni, Shuangfei ^{[1
]}

Liu, Shen ^{[1
]}

Yuan, Wen ^{[3
]}

Chen, Huajiang ^{[3
]}

Dong, Xinzhong ^{[4
,5
]}

Guan, Yun ^{[6
]}

Yang, Huilin ^{[2
]}

Cao, Xu ^{[1
]}

机构：

[1] Johns Hopkins Univ, Dept Orthopaed Surg, Baltimore, MD 21205 USA

[2] Soochow Univ, Affiliated Hosp 1, Dept Orthopaed Surg, Suzhou 215000, Jiangsu, Peoples R China

[3] Second Mil Med Univ, Changzheng Hosp, Dept Orthopaed, Sect Spine Surg, Shanghai 200433, Peoples R China

[4] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Ctr Sensory Biol, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Ctr Sensory Biol, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

15-HYDROXYPROSTAGLANDIN DEHYDROGENASE; PARTIAL-HEPATECTOMY; OSTEOBLASTIC CELLS; PGE(2) PRODUCTION; STIMULATION; INNERVATION; TISSUE; E-2; PAIN; MASS;

D O I：

10.1038/s41467-018-08097-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 beta 2-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.

引用

页数：13

共 55 条

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Interactive effects of PTH and mechanical stress on nitric oxide and PGE2 production by primary mouse osteoblastic cells [J].