Involvement of the phosphoinositide 3‐kinase/Akt signaling pathway in bone morphogenetic protein 9‐stimulated osteogenic differentiation and stromal cell‐derived factor 1 production in human periodontal ligament fibroblasts

Recent studies have shown that bone morphogenetic protein 9 (BMP‐9) can induce osteogenic differentiation in human periodontal stem cells and human periodontal ligament fibroblasts (PDLFs). Bone morphogenetic protein 9 may be used in periodontal tissue regeneration because of its potent osteoinductive ability. Human periodontal ligament cells also have been demonstrated to produce stromal cell‐derived factor 1 (SDF‐1), which is important for stem‐cell homing and recruitment to injured sites. In the present study, we examined the involvement of the phosphoinositide 3‐kinase (PI3K)/Akt signaling axis in osteogenic differentiation and SDF‐1 production in human PDLFs stimulated with BMP‐9 in osteogenic medium supplemented with dexamethasone and ascorbic acid. Pretreatment of the cells with LY294002, a PI3K‐specific inhibitor, suppressed not only BMP‐9‐enhanced alkaline phosphatase activity but also expression of a BMP‐response gene (inhibitor of DNA binding 1) and osteogenic marker genes (runt‐related transcription factor 2, osterix, bone sialoprotein, and osteopontin). In addition, BMP‐9 up‐regulated SDF‐1 production, and the production of SDF‐1 was suppressed by LY294002. The protein SDF‐1‐alpha was identified as a major isoform of SDF‐1 that was regulated by BMP‐9. Our data suggest involvement of the PI3K/Akt pathway in BMP‐9‐stimulated osteogenic differentiation and SDF‐1 production in PDLFs cultured in osteogenic medium.