The invention encompasses compositions and methods for effectively interfering, reducing and preventing conversion of vascular smooth muscle cells (VSMCs) and circulating stem cells to osteoblastic bone-like cells, thereby reducing and/or preventing vascular calcification (VC) or calcium mineral (hydroxyapatite) deposition in the vasculature. The present inventive compositions include (1) at least one agent that modulates expression and/or activity of peroxisome activated protein receptor gamma (PPAR-gamma)； (2) at least one agent that modulates expression and/or activity of one or more of the osteogenic transcription factors (Cbf-alpha-1/Runx2, Osterix, Msx2) and/or beta-catenin signaling； (3) at least one agent that modulates expression and/or activity of one or more of bone morphogenetic proteins (BMPs: BMP 2 and 4), alkaline phosphatase (ALP), and osteocalcin； (4) at least one agent that inhibits the activity of Reactive Oxygen Species (ROS)； and (5) at least one agent that suppresses one or more of inflammatory mediators including interleukins IL-1 a. IL-1b, IL-6, NF-kb, TNF-a, matrix metalloproteinases (MMPs) and prostaglandin E2 (PGE2).
