Osteogenic responses in fibroblasts activated by elastin degradation products and transforming growth factor-β1 -: Role of myofibroblasts in vascular calcification

被引：97

作者：

Simionescu, Agneta ^{[1
]}

Sirnionescu, Dan T. ^{[1
]}

Vyavahare, Narendra R. ^{[1
]}

机构：

[1] Clemson Univ, Dept Bioengn, Rhodes Ctr 501, Clemson, SC 29634 USA

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2007年 / 171卷 / 01期

关键词：

D O I：

10.2353/ajpath.2007.060930

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Our objective was to establish the role of fibroblasts in medial vascular calcification, a pathological process known to be associated with elastin degradation and remodeling. Rat dermal fibroblasts were treated in vitro with elastin degradation products and transforming growth factor (TGF)-beta 1,factors usually present in deteriorated matrix environments. Cellular changes were monitored at the gene and protein level by reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, and von Kossa staining for calcium deposits. By 21 days, multicellular calcified nodules were formed in the presence of elastin degradation products and TGF-beta 1 separately and to a significantly greater extent when used together. Before mineralization, cells expressed alpha-smooth muscle actin and large amounts of collagen type I and matrix metalloproteinase-2, characteristic features of myofibroblasts, key elements in tissue remodeling and repair. Stimulated cells expressed increased levels of core-binding factor alpha 1, osteocalcin, alkaline phosphatase, and osteoprotegerin, representative bone-regulating proteins. For most proteins analyzed, TGF-beta 1 synergistically amplified responses of fibroblasts to elastin degradation products. In conclusion, elastin degradation products and TGF-beta 1 promote myofibroblastic and osteogenic differentiation in fibroblasts. These results support the idea that elastin-related calcification involves dynamic remodeling events and suggest the possibility of a defective tissue repair process.

引用

页码：116 / 123

页数：8

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