Sensory Nerves Regulate Mesenchymal Stromal Cell Lineage Commitment by Tuning Sympathetic Tones

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2020 Mar 20

PMID 32191640

Citations 57

Authors

Bo Hu

Xiao Lv

Hao Chen

Peng Xue

Bo Gao

Xiao Wang

Gehua Zhen

Janet L Crane

Dayu Pan

Shen Liu

Shuangfei Ni

Panfeng Wu

Weiping Su

Xiaonan Liu

Zemin Ling

Mi Yang

Ruoxian Deng

Yusheng Li

Lei Wang

Ying Zhang

Mei Wan

Zengwu Shao

Huajiang Chen

Wen Yuan

Xu Cao

Affiliations

Soon will be listed here.

Abstract

The sensory nerve was recently identified as being involved in regulation of bone mass accrual. We previously discovered that prostaglandin E2 (PGE2) secreted by osteoblasts could activate sensory nerve EP4 receptor to promote bone formation by inhibiting sympathetic activity. However, the fundamental units of bone formation are active osteoblasts, which originate from mesenchymal stromal/stem cells (MSCs). Here, we found that after sensory denervation, knockout of the EP4 receptor in sensory nerves, or knockout of COX-2 in osteoblasts, could significantly promote adipogenesis and inhibit osteogenesis in adult mice. Furthermore, injection of SW033291 (a small molecule that locally increases the PGE2 level) or propranolol (a beta blocker) significantly promoted osteogenesis and inhibited adipogenesis. This effect of SW033291, but not propranolol, was abolished in conditional EP4-KO mice under normal conditions or in the bone repair process. We conclude that the PGE2/EP4 sensory nerve axis could regulate MSC differentiation in bone marrow of adult mice.

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