Ciliary parathyroid hormone signaling activates transforming growth factor-βto maintain intervertebral disc homeostasis during aging

查看全文 作　　者：Liwei [1,2]Zheng;Yong [1,3]Cao;Shuangfei [1,3]Ni;Huabin [1,4]Qi;Zemin [1,5]Ling;Xin [1,2]Xu;Xuenong [5]Zou;Tianding [1,3]Wu;Ruoxian [1]Deng;Bo [1]Hu;Bo [1]Gao;Hao [1]Chen;Yusheng [1]Li;Jianxi [1]Zhu;Francis [1,6]Tintani;Shadpour [7]Demehri;Amit [1]Jain;Khaled [1]M.Kebaish;Shenghui [8]Liao;Cheryle [9]A.Séguin;Janet [1,5]L.Crane;Mei [1]Wan;Hongbin [10]Lu;Paul [1]D.Sponseller;Lee [1]H.RileyIII;Xuedong [2]Zhou;Jianzhong [3]Hu;Xu [1]Cao

机构地区：[1]Department of Orthopedic Surgery,Johns Hopkins University School of Medicine,Ross Building,Room 229,720 Rutland Ave,Baltimore,MD,USA;[2]State Key Laboratory of Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,China;[3]Department of Spine Surgery,Xiangya Hospital,Central South University,Changsha,China;[4]Center of Bone Metabolism and Repair(CBMR),Trauma Center,Institute of Surgery Research,Daping Hospital,Third Military Medical University,Chongqing,China;[5]Guangdong Provincial Key Laboratory of Orthopedics and Traumatology,Department of Spinal Surgery,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou,China;[6]Department of Pediatrics,Johns Hopkins University School of Medicine,Ross Building,Room 229,720 Rutland Ave,Baltimore,MD,USA;[7]The Russell H.Morgan Department of Radiology and Radiological Science,Johns Hopkins University School of Medicine,Ross Building,Room 229,720 Rutland Ave,Baltimore,MD,USA;[8]Faculty of Computer Science,College of Information Science and Engineering,Xiangya Hospital,Central South University,Changsha,China;[9]Department of Physiology and Pharmacology,Schulich School of Medicine and Dentistry,University of Western Ontario,London,ON,Canada;[10]Department of Sports Medicine,Xiangya Hospital,Central South University,Changsha,China

出　　处：《Bone Research》索引2018年第6卷第3期,共14页

基　　金：supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Numbers AR071432 and AR063943 摘　　要：Degenerative disc disease(DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus(NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor(PTH1 R) to the cilia and enhances parathyroid hormone(PTH) signaling in NP cells. PTH induces transcription of integrin α_vβ_6 to activate the transforming growth factor(TGF)-β-connective tissue growth factor(CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH(iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1 R is expressed in both mouse and human NP cells. Importantly,knockout PTH1 R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1 R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD. 关键词：disc injection INTEGRIN cells IPTH effect TGF-β human

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Ciliary parathyroid hormone signaling activates transforming growth factor-βto maintain intervertebral disc homeostasis during aging

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