Osteogenic effect of interleukin-11 and synergism with ascorbic acid in human periodontal ligament cells

Background and Objective: Human periodontal ligament cells are considered to be a key cell type in the regeneration of periodontal tissues because of their unique localization and stem cell-like properties. Interleukin-11 is a multifunctional cytokine known to participate actively in bone metabolism. The purpose of this study was to examine the effect of interleukin-11 on the osteoblastic differentiation of periodontal ligament cells. Material and Methods: Cultured periodontal ligament cells were stimulated with interleukin-11 and/or ascorbic acid, with or without inhibitors for type 1 collagen, janus kinase/signal transducers and activator of transcription, and mitogen-activated protein kinase (MAPK). Osteoblastic differentiation was investigated by examining the alkaline phosphatase activity and gene expression of Runx2, osteocalcin and bone sialoprotein using reverse transcription-polymerase chain reaction. Type 1 collagen and tissue inhibitor of metalloproteinase-1 production were measured using enzyme-linked immunosorbent assays. Results: Interleukin-11 enhanced alkaline phosphatase activity and Runx2, osteocalcin and bone sialoprotein gene expression in the presence of ascorbic acid. Interleukin-11 induced type 1 collagen and tissue inhibitor of metalloproteinase-1 production in periodontal ligament cells. Type 1 collagen inhibitor completely inhibited the alkaline phosphatase activity enhanced by interleukin-11 and ascorbic acid. Furthermore, janus kinase/signal transducers and activator of transcription and MAPK signaling inhibitors reduced interleukin-11/ascorbic acid-induced alkaline phosphatase activity in periodontal ligament cells. Conclusion: Interleukin-11/ascorbic acid induced the osteoblastic differentiation of periodontal ligament cells through type 1 collagen production and janus kinase/signal transducers and activator of transcription, and MAPK signaling pathways were involved in this process. These findings suggest that interleukin-11 may function as an osteopromotive cytokine, stimulating the osteoblastic differentiation of periodontal ligament cells mainly through the synthesis of type 1 collagen and possibly by the induction of tissue inhibitor of metalloproteinase-1.