Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis

Hao Chen, Bo Hu, Xiao Lv, Shouan Zhu, Gehua Zhen, Mei Wan, Amit Jain, Bo Gao, Yu Chai, Mi Yang, Xiao Wang, Ruoxian Deng, Lei Wang, Yong Cao, Shuangfei Ni, Shen Liu, Wen Yuan, Huajiang Chen, Xinzhong Dong, Yun GuanHuilin Yang, Xu Cao

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number181
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Chen, H., Hu, B., Lv, X., Zhu, S., Zhen, G., Wan, M., Jain, A., Gao, B., Chai, Y., Yang, M., Wang, X., Deng, R., Wang, L., Cao, Y., Ni, S., Liu, S., Yuan, W., Chen, H., Dong, X., ... Cao, X. (2019). Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis. Nature communications, 10(1), [181]. https://doi.org/10.1038/s41467-018-08097-7