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MiR-143 Inhibits Osteoclastogenesis by Targeting RANK and NF-κB and MAPK Signaling Pathways

[ Vol. 13 , Issue. 3 ]

Author(s):

Xianfeng He, Limei Zhu*, Lin An and Jingwei Zhang   Pages 224 - 232 ( 9 )

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.

Keywords:

MiR-143, osteoclastogenesis, RANK, NF-κB, MAPK, TRAF6, RANK/RANKL.

Affiliation:

Department of Orthopedics, Ningbo NO.6 Hospital, Ningbo, 315040, Department of Orthopedics, Ningbo NO.6 Hospital, Ningbo, 315040, Department of Orthopedics, Ningbo NO.6 Hospital, Ningbo, 315040, Department of Orthopedics, Ningbo NO.6 Hospital, Ningbo, 315040

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