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MiR‐377 inhibits wear particle‐induced osteolysis via targeting RANKL
Author(s) -
Li Wei,
Wang Xiaomeng,
Chang Li,
Wang Fei
Publication year - 2019
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11143
Subject(s) - osteolysis , rankl , osteoclast , cathepsin k , cancer research , tumor necrosis factor alpha , chemistry , tartrate resistant acid phosphatase , bone resorption , proinflammatory cytokine , western blot , immunology , microbiology and biotechnology , inflammation , receptor , activator (genetics) , medicine , biology , biochemistry , gene , surgery
Periprosthetic osteolysis caused by wear particles is the main factor that affects the long‐term efficacy of artificial joint replacement, and macrophages play a vital role in the pathogenesis of periprosthetic osteolysis, while the potential mechanism underlying this is still unclear. To investigate the underlying role of miR‐377 in wear particle‐induced osteolysis (PIO), blood samples from patients undergoing arthroplasty were collected for analyzing the correlation between miR‐377 expression and the clinicopathological parameters of PIO. Peripheral blood macrophages were obtained to compare the miR‐377 and receptor activator of NF‐κB ligand (RANKL) expressions. Bone marrow macrophages (BMMs) following titanium (Ti) particle treatment and/or miR‐377 mimic transfection were used. The expressions of RANKL, pro‐inflammatory cytokines interleukin 6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) and the osteoclast‐related molecules tartrate‐resistant acid phosphatase (TRAP) and cathepsin K (CTSK) were determined using real‐time polymerase chain reaction or western blotting or enzyme‐linked immunosorbent assay or TRAP staining, when appropriate. The interaction between miR‐377 and RANKL was assessed by luciferase reporter assay. The in vivo role of miR‐377 in PIO was evaluated using a mouse calvarial osteolysis model. There were significant differences in downregulated miR‐377 expression between the different numbers of particles in the joint prostheses. The Ti particle treatment increased pro‐inflammatory cytokine levels, downregulated RANKL and increased osteoclast activity in BMMs, while miR‐377 overexpression led to the opposite effect. Taken together, miR‐377 downregulated the target gene RANKL, resulting in PIO inhibition. MiR‐377 relieved PIO by negatively regulating RANKL.