Abstract
Type 2 diabetes mellitus (T2DM) is a clinically important risk factor for dental implant treatment failure. An imbalance in the microenvironment of the jawbone of diabetic patients can impair the functions of bone marrow mesenchymal stem cells (BMSCs), thereby interfering with implant osseointegration during the healing phase. This study aims to investigate potential molecular factors associated with abnormal BMSC biological functions in diabetic patients with dental implant failure and identify intervention targets to improve implant osseointegration. The results of cell adhesion, cell scratch migration, alkaline phosphatase (ALP) activity, alizarin red staining, and real-time PCR assays showed that the adhesion, migration, and osteogenic differentiation abilities were significantly lower in alveolar BMSCs isolated from diabetic patients with implant failure (DM-F group) than in those isolated from diabetic patients with implant success (DM-S group) and normal patients (Nor group). Also, bioinformatics analysis and verification of whole-cell proteomics results revealed that integrin subunit alpha10 (ITGA10) expression in BMSCs was significantly lower in the DM-F group than in the DM-S group and much lower than that in the Nor group. In addition, lentiviral mediated short hairpin RNA (shRNA) or complementary DNA (cDNA) was used to knockdown or overexpress ITGA10 in BMSCs from diabetic patients, and the results revealed that ITGA10 knockdown significantly reduced the adhesion and migration abilities of BMSCs and inhibited their osteogenic differentiation potential by disturbing the FAK/PI3K/AKT/GSK3β/β-catenin pathway. ITGA10 overexpression produced the opposite results. In summary, this study revealed that low ITGA10 expression in BMSCs from the DM-F group is a major cause of cell dysfunction, including reduction in the adhesion, migration, and osteogenic differentiation abilities of BMSCs, and provided insight into the underlying mechanism. Additionally, ITGA10 was identified as a potential target protein for improving the biological functions of BMSCs and dental implant osseointegration in T2DM patients.