TY - JOUR AU - Hu, Bo AU - Lv, Xiao AU - Chen, Hao AU - Xue, Peng AU - Gao, Bo AU - Wang, Xiao AU - Zhen, Gehua AU - Crane, Janet L. AU - Pan, Dayu AU - Liu, Shen AU - Ni, Shuangfei AU - Wu, Panfeng AU - Su, Weiping AU - Liu, Xiaonan AU - Ling, Zemin AU - Yang, Mi AU - Deng, Ruoxian AU - Li, Yusheng AU - Wang, Lei AU - Zhang, Ying AU - Wan, Mei AU - Shao, Zengwu AU - Chen, Huajiang AU - Yuan, Wen AU - Cao, Xu T1 - Sensory nerves regulate mesenchymal stromal cell lineage commitment by tuning sympathetic tones PY - 2020/07/01/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI131554 VL - 130 IS - 7 UR - https://doi.org/10.1172/JCI131554 SP - 3483 EP - 3498 PB - The American Society for Clinical Investigation ER -