MiR-558 inhibits odontogenic differentiation of human periodontal ligament fibroblasts by negatively regulating Jagged-1/Notch signaling pathway

Purpose: To investigate the potential effect and explore the underlying mechanism of action of miR-558 in the odontogenic differentiation of human periodontal ligament fibroblasts (hPLFs). Methods: Human periodontal ligament fibroblasts were treated with osteogenic induction medium to induce odontogenic differentiation. The efficiency of odontogenic differentiation was determined using Alizarin red staining and alkaline phosphatase (ALP) activity assays. The expression levels of osteogenic markers, including Osterix and Runx2, were determined by Western blotting, while mRNA levels of Jagged-1, HES1 and HEY1 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Results: MiR-558 was down-regulated during the odontogenic differentiation of hPLFs. Alizarin red staining and ALP activity data indicate that miR-558 significantly inhibited the odontogenic differentiation of hPLFs. Osterix and Runx2 expression levels were significantly decreased in the miR-558 mimic group but significantly increased in miR-558 inhibitor group compared with those in NC group (p < 0.01). Moreover, miR-558 regulated Notch signaling by targeting Jagged-1, while Jagged-1 knockdown suppressed the odontogenic differentiation of hPLFs. Conclusion: MiR-558 inhibits the odontogenic differentiation of human periodontal ligament fibroblasts by negatively regulating Jagged-1/Notch signaling pathway, and thus, could serve as a potential target to regulate the odontogenic differentiation of hPLFs.