ICMRS Scientific Frontier Webinar Series
Sensory Nerve Regulates Mechanical Properties of Skeleton
Implication of Joint Disease and Pain
感觉神经调节骨骼的力学性能 : 关节脊柱疾病及疼痛的启示
Presented by Xu Cao, Ph.D.
Lee Riley Professor and Director, Center for Musculoskeletal Research
Johns Hopkins University
When: June 6, 2020 (Saturday) 9:00 PM Eastern Time (US and Canada)
June 6, 2020 (Saturday) 8:00 PM Central Time (US and Canada)
June 7, 2020 (Sunday) 9:00 AM Perth (Australia - Western Australia)
June 7, 2020 (Sunday) 11:00 AM Sydney (Australia - New South Wales)
曹旭教授于1986年赴美，1991年获得南卡罗来纳大学生物化学博士学位。嗣后在华盛顿大学从事博士后研究。1996年应聘到阿拉巴马大学病理系助理教授，副教授，教授、综合性癌症研究中心研究员。2009年应邀至美国约翰 • 霍普金斯大学Lee Rilley讲席教授，骨骼与肌肉研究中心主任。中国骨学杂志“Bone Research”创刊主编。曹旭博士主要从事骨重建机理，骨性关节炎及其他骨骼疾病的研究， 其成果发表在Nature Medicine等学术杂志上的论文100余篇。
Abstract: Skeleton provides mechanical support and metabolic mineral reserve for the animals. Bone is constantly under remodeling as a process for calcium and phosphorous metabolism. The homeostasis of this bone remodeling metabolic activity is achieved by active TGF released during osteoclast bone resorption to couple osteoblast bone formation. Moreover, IGF-1 liberated from bone matrix by osteoclasts and PDGF-BB and Netrin-1 secreted by preosteoclasts in coupling osteoblast differentiation, angiogenesis, and nerve innervation, respectively. Our recent study reveals that bone property and mass accrual for the mechanical support is primarily regulated by nerve system. Prostaglandin E2 (PGE2) is secreted osteoblastic cells regulated by mechanical stress to activates PGE2 receptor 4 (EP4) in sensory nerves, which inhibits sympathetic activity through the central nervous system to induce osteoblast differentiation for the bone formation. PGE2 levels secreted by osteoblasts increases when bone density decreases. 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 boosts bone formation, whereas the effect is obstructed in EP4 knockout mice. Thus, PGE2 mediates sensory nerve to control bone homeostasis and promote regeneration. In major skeletal disorders including osteoarthritis and low back pain, we find there are elevated levels of PGE2 which activate sensory nerves, leading to sodium influx through Nav 1.8 channels responsible for skeletal pain. Knockout of EP4 in sensory nerves or injection of COX2 inhibitor significantly reduces the skeletal pain hypersensitivity. In summary, bone metabolic activity of bone remodeling is maintained by coupling osteoclast bone resorption and osteoblast bone formation, whereas the bone mechanical properties are primarily regulated by PGE2/EP4 signaling in nerve system. Aberrant mechanical loading could lead to uncoupled bone remodeling and increase of PGE2 levels for joint disorders and pain.
This webinar will be moderated by Dr. Jean Jiang, Professor and Zachry Distinguished University Chair in the Department of Biochemistry and Structural Biology at the University of Texas Health Science Center at San Antonio.
For more information, please contact:
Jean Jiang, PhD
Chair, Education Committee, ICMRS
Professor and Zachry Distinguished University Chair
Department of Biochemistry and Structural Biology
University of Texas Health Science Center at San Antonio