Abstract
Type 2 diabetes mellitus (T2DM) is considered to compromise implant osseointegration. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates glucose metabolism, systemic inflammation, and bone regeneration. This study aimed to investigate the role of PTPN2 in implant osseointegration in T2DM and explore the potential mechanisms. Streptozotocin-induced diabetic rats received implant surgery, with or without local overexpression of PTPN2 for three months, and implant osseointegration was examined by histological evaluation, micro-CT analysis, pull-out test, and scanning electron microscope. Rat bone marrow stem cells (RBMSCs) were isolated and exposed to high glucose, and osteogenic differentiation was evaluated by alizarin red staining, ALP assay, and Western blot analysis. Overexpression of PTPN2 could improve impaired implant osseointegration in T2DM rats and promote osteogenic differentiation of RBMSCs in high glucose. In addition, p-ERK level in RBMSCs was increased in high glucose and decreased after PTPN2 overexpression. These results suggest that PTPN2 promotes implant osseointegration in T2DM rats and enhances osteogenesis of RBMSCs in high glucose medium via inducing the dephosphorylation of ERK. PTPN2 may be a novel target for the therapy of impaired implant osseointegration in T2DM patients. Impact statement: Using both in vivo and in vitro approaches, we made important findings that PTPN2 promoted implant osseointegration in T2DM rats and enhanced osteogenesis of RBMSCs in high glucose medium. The positive effects of PTPN2 on osteogenesis are related to the dephosphorylation of ERK and the inhibition of MAPK/ERK pathway. PTPN2 may be a novel target for the therapy of impaired implant osseointegration in T2DM patients.