Importantly, the results of this research suggest that six crucial miRNAs (hsa-miR-1908, hsa-miR-943, hsa-miR-203a, hsa-miR-550a-5p, hsa-miR-382-3p, and hsa-miR-376c-3p) regulate the expression of 16 genes (especially in FOS, PLS1, EXO1, and CDKN1A), thereby influencing how T2DM exerts negative effects on bone. Here, PLS1 is linked to type 2 diabetes mellitus.