Figure 6.

A) The role of neutrophils in the initiation process of bone regeneration elucidated via in vivo ectopic simulation of endochondral ossification. The ectopic implantation of IL‐8 at a high and medium level have simulated the microenvironment of bone fracture at the early and later stage, respectively. High‐level IL‐8 at the early stage led to a proinflammatory microenvironment and phagocytosis to eliminate the damaged tissue debris for inflammation resolution. Thereafter, an adequate level of IL‐8 at the later stage polarizes neutrophils to an N2‐subtype for endochondral ossification. B) Signaling pathway of BMSC recruitment by neutrophils. N2‐polarized neutrophils release SDF‐1α to recruit BMSCs via the SDF‐1/CXCR4 axis, its downstream PI3K/Akt pathway, and β‐catenin‐mediated migration.