Cartilage type IIB procollagen NH2-propeptide, PIIBNP, inhibits angiogenesis

Cartilage tissue is avascular and resistant to tumor invasion, but the basis for these properties is still unclear. Here we report that the NH₂-propeptide of type IIB procollagen (PIIBNP), a product of collagen biosynthesis, is capable of inhibiting angiogenesis both in vitro and in vivo. 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_Vß₃ and α_Vß₅ integrins are expressed primarily in endothelial cells, cancer cells and osteoclasts, but not in normal chondrocytes and PIIBNP binds to cell surface integrin α_Vß₃ and αVß₅, we propose that natural occurring PIIBNP protects cartilage by targeting endothelial cells during chondrogenesis, thus inhibiting angiogenesis, and rendering the tissue avascular.