MicroRNA-210 protects against periodontitis through targeting HIF-3α and inhibiting p38MAPK/NF-κB pathway.

ABSTRACT

The aim of this study was to investigate the effects of miR-210 abnormal expression on Porphyromonas gingivalis lipopolysaccharide (LPS)-treated primary human periodontal ligament cells (PDLCs). The miR-210 level was identified in gingival tissues from patients with chronic periodontitis (CP) and healthy subjects as well as LPS-treated PDLCs by qRT-PCR. Cell viability, apoptotic cells, expression of proteins associated with apoptosis, and release of inflammatory factors in LPS-treated PDLCs were measured using MTT assay, flow cytometry assay, western blotting and ELISA, respectively. Effects of miR-210 abnormal expression on cell viability, cell apoptosis and inflammation factors in LPS-treated PDLCs were evaluated. Afterwards, the target gene of miR-210 was identified, and the involvement of p38MAPK/NF-κB pathway with the effects of miR-210 was finally studied. The miR-210 level was significantly down-regulated in gingival tissues from CP patients as well as LPS-treated PDLCs. LPS-induced decrease of cell viability, increase of apoptosis, and release of TNF-α, IL-1ß, IL-6 and IL-8 were attenuated by miR-210 overexpression. We found that hypoxia-inducible factor (HIF)-3α was a target of miR-210, and HIF-3α overexpression partly reversed the effects of miR-210 up-regulation on cell viability, cell apoptosis and inflammation factors expression in LPS-treated PDLCs. Moreover, the phosphorylation levels of key kinases in the NF-κB and p38MAPK pathways were reduced by miR-210 via targeting HIF-3α in LPS-treated PDLCs. MiR-210 attenuated LPS-induced periodontitis, and the LPS-induced activation of the NF-κB and p38MAPK pathways was attenuated by miR-210 via targeting HIF-3α in PDLCs.