Open AccessN2‐Polarized Neutrophils Guide Bone Mesenchymal Stem Cell Recruitment and Initiate Bone Regeneration: A Missing Piece of the Bone Regeneration Puzzle
Author(s) -
Cai Bolei,
Lin Dan,
Li Yan,
Wang Le,
Xie Jirong,
Dai Taiqiang,
Liu Fuwei,
Tang Mingyue,
Tian Lei,
Yuan Yuan,
Kong Liang,
Shen Steve G. F.
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202100584
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , endochondral ossification , regeneration (biology) , stem cell , immunology , pi3k/akt/mtor pathway , medicine , biology , signal transduction , cartilage , anatomy
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 α (SDF‐1 α ) 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 β ‐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.