Cartilage type IIB procollagen NH<sub>2</sub>-propeptide, PIIBNP, inhibits angiogenesis

Abstract

<abstract> <p>Cartilage tissue is avascular and resistant to tumor invasion, but the basis for these properties is still unclear. Here we report that the NH<sub>2</sub>-propeptide of type IIB procollagen (PIIBNP), a product of collagen biosynthesis, is capable of inhibiting angiogenesis both <italic>in vitro</italic> and <italic>in vivo</italic>. PIIBNP inhibits tube formation in human umbilical vein cells (HUVEC), inhibits endogenous endothelial cell outgrowth in mouse aortic ring angiogenesis bioassay and is anti-angiogenic in the mouse cornea angiogenesis assay. As α<sub>V</sub>ß<sub>3</sub> and α<sub>V</sub>ß<sub>5</sub> integrins are expressed primarily in endothelial cells, cancer cells and osteoclasts, but not in normal chondrocytes and PIIBNP binds to cell surface integrin α<sub>V</sub>ß<sub>3</sub> and αVß<sub>5</sub>, we propose that natural occurring PIIBNP protects cartilage by targeting endothelial cells during chondrogenesis, thus inhibiting angiogenesis, and rendering the tissue avascular.</p> </abstract>