Abstract
Background and aims:
Type 2 diabetes mellitus (T2DM) is recognized as a significant risk factor affecting implant osseointegration. Our previous proteomic study revealed that Fibulin1 (FBLN1) was significantly downregulated in the alveolar bone marrow mesenchymal stem cells (BMSCs) of T2DM patients with implant failure. This study aimed to verify the effects of FBLN1 on the biological function of BMSCs and implant osseointegration in T2DM patients to identify novel intervention targets for the future development of clinical treatments.
Materials and methods:
In in vitro experiments, FBLN1 was overexpressed in BMSCs from diabetic patients via lentiviral transduction. The effects of FBLN1 on the biological functions of BMSCs were assessed via a CCK8 assay, a wound healing assay, a Transwell assay, alkaline phosphatase staining, alizarin red staining, and subcutaneous osteogenesis analysis using nude mice. The molecular mechanism by which FBLN1 acts on BMSCs was verified via RT-qPCR and western blotting. In in vivo experiments, the effect of FBLN1 on implant osseointegration in diabetic GK rats through cell sheet-implant complexes was verified by microcomputed tomography and toluidine blue staining.
Results:
FBLN1 was expressed in BMSCs at an early stage of the osteogenic process. CCK8, wound healing, and Transwell assays indicated that the overexpression of FBLN1 increased the proliferation and migration of BMSCs. Alkaline phosphatase staining, alizarin red staining and subcutaneous osteogenesis analysis revealed that the overexpression of FBLN1 enhanced the osteogenic differentiation of BMSCs, and RT-qPCR and western blotting revealed that FBLN1 affected this process through the FOXO1/RUNX2 signalling pathway. Microcomputed tomography and toluidine blue staining revealed that after the implantation of cell sheet-implant complexes in rats, overexpressing FBLN1 in BMSCs could restore the level of implant osseointegration in GK rats to a level similar to that in Wistar rats.
Conclusions:
FBLN1 enhances the proliferation and migration of BMSCs from T2DM patients and promotes osteogenic function through the FOXO1/RUNX2 signalling pathway. Moreover, FBLN1 promotes implant osseointegration in diabetic GK rats, suggesting that FBLN1 is a novel target protein for increasing the success rate of dental implant surgery in T2DM patients.