文献类型：期刊文献

英文题名：N2-Polarized Neutrophils Guide Bone Mesenchymal Stem Cell Recruitment and Initiate Bone Regeneration: A Missing Piece of the Bone Regeneration Puzzle

作者：Cai, Bolei[1,2,3,4,5];Lin, Dan[1,2];Li, Yan[6,7,8];Wang, Le[1,2];Xie, Jirong[1,2,9];Dai, Taiqiang[3,4,5];Liu, Fuwei[3,4,5];Tang, Mingyue[3,4,5];Tian, Lei[1,2];Yuan, Yuan[10,11];Kong, Liang[3,4,5];Shen, Steve G. F.[1,2,12]

机构：[1]Shanghai Jiao Tong Univ, Dept Oral & Craniomaxillofacial Surg, Nal Clin Res Ctr Oral Dis,Sch Med,Coll Stomatol, Shanghai Key Lab Stomatol,Shanghai Peoples Hosp 9, Shanghai 200011, Peoples R China;[2]Shanghai Res Inst Stomatol, Shanghai 200011, Peoples R China;[3]Fourth Mil Med Univ, State Key Lab Mil Stomatol, Dept Oral & Maxillofacial Surg, Sch Stomatol, Xian 710032, Peoples R China;[4]Fourth Mil Med Univ, Natl Clin Res Ctr Oral Dis, Dept Oral & Maxillofacial Surg, Sch Stomatol, Xian 710032, Peoples R China;[5]Fourth Mil Med Univ, Shaanxi Key Lab Oral Dis, Dept Oral & Maxillofacial Surg, Sch Stomatol, Xian 710032, Peoples R China;[6]Fourth Mil Med Univ, State Key Lab Mil Stomatol, Dept Prosthodont, Sch Stomatol, Xian 710032, Peoples R China;[7]Fourth Mil Med Univ, Natl Clin Res Ctr Oral Dis, Dept Prosthodont, Sch Stomatol, Xian 710032, Peoples R China;[8]Fourth Mil Med Univ, Shaanxi Key Lab Oral Dis, Dept Prosthodont, Sch Stomatol, Xian 710032, Peoples R China;[9]Jiamusi Univ, Sch Stomatol, Dept Prosthodont, Jiamusi 154003, Peoples R China;[10]East China Univ Sci & Technol, Key Lab Ultrafine Mat, Minist Educ, Sch Mat Sci & Engn, Shanghai 200237, Peoples R China;[11]East China Univ Sci & Technol, Engn Res Ctr Biomed Mat, Minist Educ, Shanghai 200237, Peoples R China;[12]Shanghai Univ Med & Hlth Sci, Shanghai 201318, Peoples R China

年份：2021

卷号：8

期号：19

外文期刊名：ADVANCED SCIENCE

收录：;EI(收录号：20213310763540);WOS:【SCI-EXPANDED(收录号:WOS:000684083600001)】；

基金：B.C., D.L., and Y.L. contributed equally to this work. B.C., D.L., and Y.L. are joint first authors. The authors gratefully acknowledge the support of the National Natural Science Foundation of China (No. 81970973, No. 81771036, No. 81970977), China Postdoctoral Science Foundation (2020T130422), National Key R&D Program of China (No. 2017YFB1104100), and Shanghai Sailing Program (19YF1425500).

语种：英文

外文关键词：bone regeneration; interleukin-8; neutrophils; stem cell recruitment; stromal cell-derived factor-1 alpha

摘要：The role of neutrophils in bone regeneration remains elusive. In this study, it is shown that intramuscular implantation of interleukin-8 (IL-8) (commonly recognized as a chemotactic cytokine for neutrophils) at different levels lead to outcomes resembling those of fracture hematoma at various stages. Ectopic endochondral ossification is induced by certain levels of IL-8, during which neutrophils are recruited to the implanted site and are N2-polarized, which then secrete stromal cell-derived factor-1 alpha (SDF-1 alpha) for bone mesenchymal stem cell (BMSC) chemotaxis via the SDF-1/CXCR4 (C-X-C motif chemokine receptor 4) axis and its downstream phosphatidylinositol 3'-kinase (PI3K)/Akt pathway and beta-catenin-mediated migration. Neutrophils are pivotal for recruiting and orchestrating innate and adaptive immunocytes, as well as BMSCs at the initial stage of bone healing and regeneration. The results in this study delineate the mechanism of neutrophil-initiated bone regeneration and interaction between neutrophils and BMSCs, and innate and adaptive immunities. This work lays the foundation for research in the fields of bone regenerative therapy and biomaterial development, and might inspire further research into novel therapeutic options.