Cartilage Formation and Calcification in Arteries of Mice Lacking Matrix Gla Protein

• Published in: Connective tissue research Vol. 44; no. 1; pp. 272 - 278
• Main Authors: El-Maadawy, S., Kaartinen, M. T., Schinke, T., Murshed, M., Karsenty, G., McKee, M. D.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 2003; Taylor & Francis
• Subjects: Actins - metabolism; Animals; Animals, Newborn; Aorta, Thoracic - metabolism; Aorta, Thoracic - pathology; Biomineralization; Blotting, Western; Calcinosis - metabolism; Calcinosis - pathology; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cartilage; Cell Differentiation; Cell Transformation; Chondrocytes - metabolism; Chondrocytes - pathology; Extracellular Matrix Proteins; Immunohistochemistry; Matrix Gla Protein; Mice; Mice, Knockout; Mice, Transgenic; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Tunica Media - metabolism; Tunica Media - pathology; Vascular Calcification
• ISSN: 0300-8207; 1607-8438
• DOI: 10.1080/03008200390181762

Matrix Gla protein (MGP/Mgp) is a protein expressed predominantly by vascular smooth muscle cells (VSMCs) and by chondrocytes. Transgenic mice lacking Mgp die 1-3 months after birth due to calcification of elastic fibers and rupture of large elastic arteries such as the aorta [6]. Here, we report on cartilage formation that commonly occurs in calcified arteries of Mgp &#109 / &#109 mice. Using histology, von Kossa staining, immunohistochemistry, and Western blotting, together with examination of cellular markers for VSMCs and extracellular matrix markers for cartilage, we provide evidence for cell transformation from VSMC to chondrocyte in the arterial media in the absence of Mgp. At 2 weeks of age in the aorta of Mgp &#109 / &#109 mice, VSMCs lose immunostaining for smooth muscle &#102 -actin concomitant with the appearance of cartilage molecules as shown by immunohistochemical staining and Western blotting for aggrecan, link protein, and type II collagen. These data provide evidence that the absence of Mgp, and/or calcification of the ECM, in the arterial media can trigger chondrocyte differentiation and cartilage formation in blood vessels.