The RANKL/RANK/OPG Signaling Pathway Mediates Medial Arterial Calcification in Diabetic

OBJECTIVE—The receptor activator of nuclear factor-kB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) sig-naling pathway (RANKL/RANK/OPG signaling) is implicated in the osteolysis associated with diabetic Charcot neuroarthropathy (CN); however, the links with medial arterial calcification (MAC) seen in people with CN are unclear. This study aimed to investi-gate the role of RANKL/OPG in MAC in patients with CN. RESEARCH DESIGN AND METHODS—Enzyme-linked im-munosorbent assay and Bio-plex multiarray technology were used to quantify a range of cytokines, including RANKL and OPG in sera from 10 patients with diabetes, 12 patients with CN, and 5 healthy volunteers. Human tibial artery segments were immuno-histochemically stained with Alizarin red and human RANKL antibody. Human vascular smooth muscle cells (VSMCs) were also explanted from arterial segments for in vitro studies