Factors related to the osteogenic transdifferentiation of vascular smooth muscle cells in chronic kidney disease (CKD). Hyperphosphatemia stimulates the secretion of FGF-23 from osteocytes in the bone, which inhibit the activity of angiotensin-converting enzyme 2 (ACE2). FGF23 blocks the conversion of angiotensin II into angiotensin (1-7). Therefore, angiotensin II will enhance the production of aldosterone. Phosphate and calcium stimulate the Na-Pi cotransporter, and aldosterone also contributes to activate the Na-Pi cotransporter, resulting in increased phosphate entrance into VSMCs. In addition, aldosterone accentuates the inflammatory status in part by TNF. Both oxidative/inflammatory status and increased intracellular phosphate levels promote VSMCs to transdifferentiate into phenotypic osteoblast cells, which causes the ossification of the vascular wall to progress. As a whole, the calcified vessels have more prominent bone formation characteristic than bone resorption ones. In addition, osteogenic cells may secrete sclerostin (SOST) and FGF23. The secreted FGF23 from the calcified vessel may contribute further increased FGF23 serum levels.
