Periostin reverses high glucose-inhibited osteogenesis of periodontal ligament stem cells via AKT pathway.

AIMS: Diabetes mellitus leads to impaired osteogenic differentiation and alveolar bone absorption. Periostin (POSTN) is important for bone and tooth maintenance. This study aims to elucidate the expression of POSTN in high glucose and the effects of both high glucose and POSTN on osteogenesis in hPDLSCs, as well as the underlying mechanism.

MAIN

METHODS

Cells were incubated with glucose under physiological (5.5 mM normal glucose) or diabetic (30 mM high glucose) conditions in the presence or absence of recombinant human POSTN (rPOSTN). Cell migration was assessed by a scratch assay. Reactive oxygen species (ROS) was used to assess HG-induced oxidative damage. Osteogenesis was evaluated by alkaline phosphatase (ALP) activity and ALP staining, Alizarin Red staining (ARS), as well osteogenic related genes and proteins.

KEY FINDINGS: POSTN expression was inhibited during a long-term culture with HG. HG diminished the migration and osteogenesis of hPDLSCs as indicated by decreases in ALP activity and ALP staining, ARS and expression of COL I, RUNX2, OSX, OPN and OCN, but an increase in reactive oxygen species overproduction. All of which were reversed by addition of rPOSTN. POSTN knockdown suppressed migration and osteogenesis of hPDLSCs. Moreover, HG inhibited activation of AKT, which was rescued by addition of POSTN. AKT inhibitor significantly reduced POSTN-mediated osteogenic differentiation.

SIGNIFICANCE: rPOSTN could be a therapeutic regime for defective periodontal and peri-implant bone regeneration in diabetes mellitus.