Abstract
Hyperlipidemia adversely affects bone metabolism, often resulting in compromised osseointegration and implant loss. In addition, genetic networks associated with osseointegration have been proposed. Serologically defined colon cancer antigen 3 (Sdccag3) is a novel endosomal protein that functions in actin cytoskeleton remodeling, protein trafficking and secretion, cytokinesis, and apoptosis, but its roles in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and in implant osseointegration under hyperlipidemic conditions have not been uncovered. Here, we performed microarray and RNA sequencing analysis to determine the differential expression of the Sdccag3 gene and related noncoding RNAs (ncRNAs) and to assess the long noncoding RNA (lncRNA) MSTRG.97162.4-miR-193a-3p-Sdccag3 coexpression network in bone tissues within the region 0.5 mm around implants in hyperlipidemic rats. In this experiment, we found that Sdccag3 and the previously uncharacterized lncRNA-MSTRG.97162.4 were downregulated during hyperlipidemia, while miR-193a-3p was upregulated. Sdccag3 overexpression increased new trabecular formation, the bone volume/total volume (BV/TV) (1.24-fold), and bone-implant combination ratio (BIC%) (1.26-fold). An RNA pulldown experiment revealed that Sdccag3 protein targeted lncRNA-MSTRG.97162.4 nucleotides 361 to 389. In addition, lncRNA-MSTRG.97162.4 overexpression significantly enhanced Sdccag3 (2.78-fold) expression and increased BV/TV (1.45-fold) and BIC% (1.07-fold) at the bone-implant interface. Taken together, these findings indicate that Sdccag3 overexpression enhances implant osseointegration under hyperlipidemic conditions by binding to lncRNA-MSTRG.97162.4. Furthermore, miR-193a-3p overexpression inhibited lncRNA-MSTRG.97162.4 (0.63-fold) and Sdccag3 (0.88-fold) expression and induced poor implant osseointegration (BV/TV, 0.86-fold; BIC%, 0.82-fold), while miR-193a-3p downregulation produced the opposite results (lncRNA-MSTRG.97162.4, 10.69-fold; Sdccag3, 6.96-fold; BV/TV, 1.20-fold; BIC%, 1.26-fold). Therefore, our findings show that Sdccag3 promotes implant osseointegration, and its related lncRNA-MSTRG.97162.4 and miR-193a-3p play an important role in osseointegration during hyperlipidemia, which might be a promising therapeutic target for improving dental implantation success rates.