SPP1 and Hyperglycemia: During the osteogenic differentiation of VSMC, hyperglycemia upregulates expression of osteopontin (OPN) and osteoprotegerin (OPG) and then activates Msh homeobox-2 (MSX2) and Runt-related transcription factor 2 (RUNX2) through the wingless - type MMTV integration site family (WNT)/β-catenin and bone morphogenetic protein-2 (BMP-2) pathways (11–14).