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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Alkaline Phosphatase, Calcinosis, Cells, Cultured, Decorin, Gene Expression Regulation, Homeodomain Proteins, Humans, Lipoproteins, LDL, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Osteogenesis, Oxidative Stress, Pentosyltransferases, Phosphorylation, RNA Interference, Signal Transduction, Smad2 Protein, Time Factors, Transforming Growth Factor beta1.
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Do decorin GAG synthesis and TGF-β signaling mediate Ox-LDL-induced mineralization of human vascular smooth muscle cells? Context: Decorin and oxidized low-density lipoprotein (Ox-LDL) independently induce osteogenic differentiation of vascular smooth muscle cells (VSMCs). We aimed to determine whether decorin glycosaminoglycan (GAG) chain synthesis contributes to Ox-LDL-induced differentiation and calcification of human VSMCs in vitro. Human VSMCs treated with Ox-LDL to induce oxidative stress showed increased alkaline phosphatase (ALP) activity, accelerated mineralization, and a difference in both decorin GAG chain biosynthesis and CS/DS structure compared with untreated controls. Ox-LDL increased mRNA abundance of both xylosyltransferase (XT)-I, the key enzyme responsible for GAG chain biosynthesis and Msx2, a marker of osteogenic differentiation. Furthermore, downregulation of XT-I expression using small interfering RNA blocked Ox-LDL-induced VSMC mineralization. Adenoviral-mediated overexpression of decorin, but not a mutated unglycanated form, accelerated mineralization of VSMCs, suggesting GAG chain addition on decorin is crucial for the process of differentiation. The decorin-induced VSMC osteogenic differentiation involved activation of the transforming growth factor (TGF)-β pathway, because it was attenuated by blocking of TGF-β receptor signaling and because decorin overexpression potentiated phosphorylation of the downstream signaling molecule smad2.
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These studies provide direct evidence that oxidative stress-mediated decorin GAG chain synthesis triggers TGF-β signaling and mineralization of VSMCs in vitro. Final Decision: yes