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Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis.
Chen, Hao; Hu, Bo; Lv, Xiao; Zhu, Shouan; Zhen, Gehua; Wan, Mei; Jain, Amit; Gao, Bo; Chai, Yu; Yang, Mi; Wang, Xiao; Deng, Ruoxian; Wang, Lei; Cao, Yong; Ni, Shuangfei; Liu, Shen; Yuan, Wen; Chen, Huajiang; Dong, Xinzhong; Guan, Yun; Yang, Huilin; Cao, Xu.
Affiliation
  • Chen H; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Hu B; Department of Orthopaedic Surgery, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, P. R. China.
  • Lv X; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Zhu S; Section of Spine Surgery, Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, P. R. China.
  • Zhen G; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Wan M; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Jain A; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Gao B; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Chai Y; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Yang M; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Wang X; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Deng R; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Wang L; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Cao Y; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Ni S; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Liu S; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Yuan W; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Chen H; Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Dong X; Section of Spine Surgery, Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, P. R. China.
  • Guan Y; Section of Spine Surgery, Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, P. R. China.
  • Yang H; Howard Hughes Medical Institute and The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Cao X; Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Nat Commun ; 10(1): 181, 2019 01 14.
Article in En | MEDLINE | ID: mdl-30643142
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 ß2-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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteoporosis / Sensory Receptor Cells / Bone and Bones / Dinoprostone / Receptors, Prostaglandin E, EP4 Subtype Type of study: Etiology_studies Limits: Animals / Female / Humans / Male Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2019 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteoporosis / Sensory Receptor Cells / Bone and Bones / Dinoprostone / Receptors, Prostaglandin E, EP4 Subtype Type of study: Etiology_studies Limits: Animals / Female / Humans / Male Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2019 Document type: Article Affiliation country: Country of publication: