Integrin α10 regulates adhesion, migration, and osteogenic differentiation of alveolar bone marrow mesenchymal stem cells in type 2 diabetic patients who underwent dental implant surgery

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.

Characterisation and Expression of Osteogenic and Periodontal Markers of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) from Diabetic Knee Joints

“…Higher ALP staining intensity was observed in cultures of ND vs. D BM-MSCs ( Figure 3 ), which agrees with the work of Sun et al [ 26 ] and Liang et al [ 43 ], who reported lower ALP staining and activity in cultures of alveolar bone BM-MSCs isolated from D vs. ND donors. Thus, D BM-MSCs potentially show lower levels of ALP activity despite variation in the anatomical source.…”

Long non‐coding RNA AC018926.2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway

“…Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was utilized to investigate the signalling pathways that may be impacted by AC018926.2 . Figure 5C shows the top 10 enriched signalling pathways, among which the focal adhesion and phosphatidylinositol 3‐kinase (PI3K)/AKT signalling pathways, which are closely related to cell osteogenesis, were significantly downregulated in the si‐ AC018926.2 group and identified 39,40 . Therefore, we hypothesized that silence of AC018926.2 could inhibit the osteogenic process of PDLSCs by inactivating the FAK/PI3K/AKT signalling pathway.…”

“…From the results of RNA sequencing and KEGG analysis, we found that the FAK and PI3K/AKT pathway were significantly downregulated following AC018926.2 knockdown (Figure 5C). Previous studies have shown that activation of the FAK/PI3K/AKT pathway is positively associated with cell osteogenic differentiation 39,40 . As an important member of the integrin family, ITGA2 has been reported to enhance the osteogenic capacity of cells by activating the FAK signalling pathway 43,44 .…”

Functionalization of zirconia ceramic with fibronectin proteins enhanced bioactivity and osteogenic response of osteoblast-like cells

“…Yu-Hua Pan et al, also showed in a comparison between control and GDP-treated zirconia disks that increased surface roughness is associated with higher contact angle ( Pan et al, 2020 ). In the current study, the major objective was functionalization with fibronectin proteins to enhance osteoblastic-like cell adhesion and proliferation ( Chang et al, 2016b ; Liang et al, 2022 ) in combination with improved physical properties of surface roughness and wettability of zirconia ceramic.…”