Affiliation:
1. Department of Orthopedics, Ningbo NO.6 Hospital, Ningbo, 315040, China
Abstract
Objective:
To explore the effect of miRNA-143 on osteoclast formation and provide new
ideas for the treatment of osteoporosis.
Methods:
Mice macrophage lines RAW264.7 cells after transfection were divided into four groups:
control group, RANKL group, RANKL combined with miR-143 mimics group and RANKL combined
with miR-NC group. TARCP staining was used to observe the effect of miR-143 on osteoclast formation.
The expression of RANK, TRAF6 and NFATc-1 in the upstream of RANKL pathway was detected
by real-time quantitative PCR (RT qPCR) and Western blotting (WB). The binding of miR-143
to TNFRSF11A was detected by double Luciferase Reporter Analysis. The effect of miR-143 on the
expression of NF-κB (p65, I-κB-α) signal pathway in osteoclasts was detected. The effects of I-BET151
on the expression of osteoclast-specific genes TRACP, MMP 9, CtsK and c-Src were detected.
Results:
The positive level of osteoclasts in RANKL group and RANKL combined with miR-NC group
was significantly higher than that of RANKL combined with miR-143 mimics group and control group
(P < 0.05). The expression levels of RANK, TRAF6, NFATc-1, TRACP, MMP-9, CtsK and c-Src in
RANKL group and RANKL combined with miR-NC group were significantly higher than those of
RANKL combined with miR-143 mimics group and control group (P < 0.05). The expression levels of
I-κB-α were significantly lower than that of RANKL combined with miR-143 mimics group and control
group (P<0.05).
Conclusion:
MiR-143 can inhibit the expression of RANK, TRAF6 and downstream NFATc-1 in the
RANKL pathway, thereby inhibiting the RANK/RANKL pathway. MiR-143 can inhibit the signal
pathway of NF-κB (p65, I-κB-α). MiR-143 inhibits the expression of osteoclast-specific genes TRACP,
MMP 9, CtsK and c-Src. That is to say, miR-143 inhibits osteoclast formation by targeting RANK, NF-
κB and MAPK signaling pathways.
Publisher
Bentham Science Publishers Ltd.
Subject
General Health Professions
Cited by
4 articles.
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