Elastin-derived peptides and TGF-beta1 induce osteogenic responses in smooth muscle cells.
Elastin degradation associated with matrix metalloproteinase activity is a cell-mediated process, observed in almost all types of vascular calcification. In this study, we tested the hypothesis that elastin-derived peptides induce an osteogenic response in vascular smooth muscle cells (SMCs) in vitro. Using RT-PCR and specific protein assays, we demonstrated that rat aortic SMCs incubated with elastin peptides exhibited an increased expression of the 67 kDa elastin laminin receptor (ELR) and matrix metalloproteinase-2 and typical bone proteins, such as core binding factor alpha-1, osteocalcin, and alkaline phosphatase. The osteogenic gene expression in SMCs was further enhanced by the addition of TGF-beta1 along with the elastin peptides, in the absence of any other mineralizing agent. Conversely, lactose (an ELR antagonist) down-regulated expression of most investigated proteins. In conclusion, elastin-derived peptides and TGF-beta1 up-regulate the expression of typical bone proteins in cultured rat aortic SMCs, possibly via the ELR signaling.
Simionescu
Agneta
A
Department of Bioengineering, Clemson University, Clemson, SC 29634, USA.
Philips
Katherine
K
Vyavahare
Narendra
N
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D019485:Bone Morphogenetic Proteins; D010446:Peptide Fragments; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004549:Elastin