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

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Abstract
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.

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