Sensory nerve was recently identified as being involved in regulation of bone mass accrual. We previously discovered that PGE2 secreted by osteoblastic cells 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 skeletal stem cells. Here, we found that after sensory denervation, knockout of the EP4 receptor in sensory nerves, or knockout of cyclooxygenase-2 (COX2) in osteoblasts could significantly promote adipogenesis and inhibit osteogenesis in adult mice. Furthermore, injection of SW033291 (a small molecule that locally increases 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 knockout mice under normal conditions or in the bone repair process. We conclude that the PGE2-EP4 sensory nerve axis could regulate skeletal stem cell differentiation in bone marrow of adult mice.
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