Premium
miR ‐34a carried by adipocyte exosomes inhibits the polarization of M1 macrophages in mouse osteolysis model
Author(s) -
Gao XuRen,
Ge Jian,
Li WeiYi,
Zhou WangChen,
Xu Lei,
Geng Deqin
Publication year - 2021
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.37088
Subject(s) - osteolysis , macrophage polarization , macrophage , cancer research , materials science , microbiology and biotechnology , chemistry , medicine , biology , in vitro , biochemistry , dentistry
Objective After bone prosthesis replacement, M1‐type macrophage polarization can be induced by titanium (Ti) particles and produce inflammatory, leading to osteolysis. Adipocyte‐derived exosomes (ADEs) exert immune‐modulatory impact on the macrophage, while whether it can inhibit the macrophage polarization induced by Ti is unclear. This study focuses on the M1‐type macrophage and aims to determine the effect of ADEs on Ti‐induced M1‐type macrophage polarization in osteolytic mice and the involved mechanism. Methods Ti particle‐induced osteolysis mouse model was established and macrophages were isolated from the osteolysis site. The levels of NLRP3 and specific markers for M1‐type macrophage were determined. ADEs isolated from adipocyte cell line 3T3‐L1, or conditioned ADEs with low‐expressed miR‐34a isolated from 3T3‐L1 transfected with miR‐34a inhibitor were co‐cultured with RAW 264.7 to determine their impact on the polarization of macrophage. Results ADEs reduced the M1‐type macrophage polarization and caused the upregulation of miR‐34a in macrophage of the osteolysis site of the osteolysis mouse model. Also, the level of miR‐34a in ADEs was higher than that in the adipocyte. The conditioned ADEs expressed a low level of miR‐34a and boosted the Ti‐induced M1‐type polarization. MiR‐34a could target NLRP3 and negatively regulated its expression. Moreover, NLRP3 knockdown in macrophage restricted the conditioned ADEs to promote macrophage towards to Ti‐induced M1‐type polarization. The inhibitory function of ADEs on M1‐type macrophage polarization was abolished by miR‐34a silencing in the mouse osteolysis model. Conclusion The miR‐34a carried by ADEs reduced the polarization of M1‐type macrophages by targeting macrophage NLRP3 during Ti particle‐induced osteolysis.