Immunopharmacology and immunotoxicology · 2018
miR-130b participates in wear particle-induced inflammation and osteolysis via FOXF2/NF-κB pathway.
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Zheng De-Zhi, Bu Yan-Min, Wang Lei
Аннотация
OBJECTIVE: To reveal other miR-130b-mediated signaling pathway in the involvement of wear particle-induced inflammation and osteolysis.
MATERIALS AND METHODS: Particle-induced osteolysis (PIO) mice model was established. Secretion levels of TNF-α, IL-1β, IL-6, and IL-10 were measured by ELISA. miR-130b and forkhead box F2 (FOXF2) mRNA were detected by qRT-PCR. Protein levels of FOXF2, phosphorylation-p65 (p-p65), and p-IκB were observed by Western blot. Luciferase reporter assay was performed to confirm the regulation of miR-130b on FOXF2.
RESULTS: Compared with normal mice, secretion levels of TNF-α, IL-1β, and IL-6 in PIO mice were significantly up-regulated and IL-10 was significantly down-regulated; miR-130b and p-p65 expressions were up-regulated and FOXF2 expression was down-regulated. In addition, the trends of miR-130b, FOXF2, and p-p65 expressions in Co-Cr-Mo treated Raw264.7 cells were the same as that in PIO mice. After transfection with miR-130b inhibitor, secretion levels of TNF-α, IL-1β, and IL-6 in Raw264.7 cells were significantly decreased and secretion level of IL-10 was significantly increased. We also proved FOXF2 was a target of miR-130b, and FOXF2 siRNA increased secretion levels of TNF-α, IL-1β, and IL-6 and decreased secretion level of IL-10. Finally, we found nuclear factor-kappa B (NF-κB) inhibitor BAY 11-7082 further decreased secretion levels of TNF-α, IL-1β, and IL-6 and increased IL-10 level.
CONCLUSION: The role of miR-130b/FOXF2/NF-κB pathway in PIO was firstly revealed, which provided new targets for the treatment of periprosthetic osteolysis.
MATERIALS AND METHODS: Particle-induced osteolysis (PIO) mice model was established. Secretion levels of TNF-α, IL-1β, IL-6, and IL-10 were measured by ELISA. miR-130b and forkhead box F2 (FOXF2) mRNA were detected by qRT-PCR. Protein levels of FOXF2, phosphorylation-p65 (p-p65), and p-IκB were observed by Western blot. Luciferase reporter assay was performed to confirm the regulation of miR-130b on FOXF2.
RESULTS: Compared with normal mice, secretion levels of TNF-α, IL-1β, and IL-6 in PIO mice were significantly up-regulated and IL-10 was significantly down-regulated; miR-130b and p-p65 expressions were up-regulated and FOXF2 expression was down-regulated. In addition, the trends of miR-130b, FOXF2, and p-p65 expressions in Co-Cr-Mo treated Raw264.7 cells were the same as that in PIO mice. After transfection with miR-130b inhibitor, secretion levels of TNF-α, IL-1β, and IL-6 in Raw264.7 cells were significantly decreased and secretion level of IL-10 was significantly increased. We also proved FOXF2 was a target of miR-130b, and FOXF2 siRNA increased secretion levels of TNF-α, IL-1β, and IL-6 and decreased secretion level of IL-10. Finally, we found nuclear factor-kappa B (NF-κB) inhibitor BAY 11-7082 further decreased secretion levels of TNF-α, IL-1β, and IL-6 and increased IL-10 level.
CONCLUSION: The role of miR-130b/FOXF2/NF-κB pathway in PIO was firstly revealed, which provided new targets for the treatment of periprosthetic osteolysis.