Traumatic brain injury stimulates sympathetic tone-mediated bone marrow myelopoiesis to favor fracture healing

作     者：Weijian Liu Wei Chen Mao Xie Chao Chen Zengwu Shao Yiran Zhang Haiyue Zhao Qingcheng Song Hongzhi Hu Xin Xing Xianyi Cai Xiangtian Deng Xinyan Li Peng Wang Guohui Liu Liming Xiong Xiao Lv Yingze Zhang Weijian Liu;Wei Chen;Mao Xie;Chao Chen;Zengwu Shao;Yiran Zhang;Haiyue Zhao;Qingcheng Song;Hongzhi Hu;Xin Xing;Xianyi Cai;Xiangtian Deng;Xinyan Li;Peng Wang;Guohui Liu;Liming Xiong;Xiao Lv;Yingze Zhang

作者机构：Department of OrthopaedicsUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Orthopaedic SurgeryThe Third Hospital of Hebei Medical UniversityShijiazhuang 050051China School of MedicineNankai UniversityTianjin 300071China NHC Key Laboratory of Intelligent Orthopeadic EquipmentThird Hospital of Hebei Medical UniversityShijiazhuang 050051China Animal Center of Hebei Ex&In vivo BiotechnologyShijiazhuang 050051China Department of PhysiologySchool of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2023年第8卷第8期

页      面：3751-3767页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：This study was partly supported by the National Natural Science Foundation of China(91949203 to Zhang Y.Z.,82102627 to Lv X.) Key Project of Hebei Provincial Natural Fund(H2020206456) Hubei Provincial Natural Science Foundation of China(2021CFB095) Wuhan Knowledge Innovation Project 2022020801020468 

主　　题：healing inflammation Traumatic 

摘      要：Traumatic brain injury(TBI)accelerates fracture healing,but the underlying mechanism remains largely *** evidence indicates that the central nervous system(CNS)plays a pivotal role in regulating immune system and skeletal ***,the impact of CNS injury on hematopoiesis commitment was ***,we found that the dramatically elevated sympathetic tone accompanied with TBI-accelerated fracture healing;chemical sympathectomy blocks TBIinduced fracture ***-induced hypersensitivity of adrenergic signaling promotes the proliferation of bone marrow hematopoietic stem cells(HSCs)and swiftly skews HSCs toward anti-inflammation myeloid cells within 14 days,which favor fracture *** ofβ3-orβ2-adrenergic receptor(AR)eliminate TBI-mediated anti-inflammation macrophage expansion and TBIaccelerated fracture *** sequencing of bone marrow cells revealed that Adrb2 and Adrb3 maintain proliferation and commitment of immune ***,flow cytometry confirmed that deletion ofβ2-AR inhibits M2 polarization of macrophages at 7th day and 14th day;and TBI-induced HSCs proliferation was impaired inβ3-AR knockout ***,β3-andβ2-AR agonists synergistically promote infiltration of M2 macrophages in callus and accelerate bone healing ***,we conclude that TBI accelerates bone formation during early stage of fracture healing process by shaping the anti-inflammation environment in the bone *** results implicate that the adrenergic signals could serve as potential targets for fracture management.