Mangiferin (MAG) is a polyphenolic compound present in mangoes. This compound suppresses inflammation and decreases bone destruction. This study aimed to determine whether MAG directly promotes proliferation and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Cell proliferation and osteogenic differentiation experiments were performed in hPDLSCs, and MAG was used as a stimulator during osteogenic induction. Alkaline phosphatase (ALP) activity and Alizarin red staining were analyzed, and the expression of osteogenesis‑associated genes was investigated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis to determine the effect of MAG on the osteogenic differentiation of hPDLSCs. Galunisertib was used to selectively inhibit TGF‑β/SMAD2 signaling. Western blotting was performed to study the underlying mechanism. Cell Counting Kit‑8 assay showed that MAG did not promote the proliferation of hPDLSCs. MAG (200 µM) significantly promoted ALP activity, mRNA levels of alkaline phosphatase biomineralization associated, collagen type 1, and runt‑related transcription factor‑2, protein levels of SMAD5, alkaline phosphatase and bone morphogenetic protein 2 protein expression and mineralized nodule formation in hPDLSCs. Furthermore, MAG significantly promoted the phosphorylation of SMAD2. Galunisertib inhibited the activation of SMAD2 and partially reversed the MAG‑mediated promotion of hPDLSC osteogenic differentiation. These data indicated that MAG promoted osteogenic differentiation of hPDLSCs potentially through TGF‑β/SMAD2 signaling. Therefore, MAG may help improve periodontal bone loss.
Keywords: SMAD2; mangiferin; osteogenic; periodontal ligament stem cells.