Matrix metalloproteases from chondrocytes generate an antiangiogenic 16 kDa prolactin

• DOI: 10.1242/jcs.02887
• Publication Date: 2006-04-12T01:33:44Z
• Authors: Yazmín Macotela; Manuel B. Aguilar; Jessica Guzmán-M...; José C. Rivera; Consuelo Zermeño; Fernando López-B...; Gabriel Nava; Carlos Lavalle; Gonzalo Martínez...; Carmen Clapp
• Keywords: Male; 0301 basic medicine; Molecular Sequence Data; Angiogenesis Inhibitors; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Peptide Fragments; Prolactin; Rats; Molecular Weight; 03 medical and health sciences; Chondrocytes; Culture Media, Conditioned; Animals; Humans; Amino Acid Sequence; RNA, Messenger; Rats, Wistar; Cells, Cultured

The 16 kDa N-terminal fragment of prolactin (16K-prolactin) is a potent antiangiogenic factor. Here, we demonstrate that matrix metalloproteases (MMPs) produced and secreted by chondrocytes generate biologically functional 16K-prolactin from full-length prolactin. When incubated with human at neutral pH, chondrocyte extracts conditioned medium, as well in culture, cleaved the Ser155-Leu156 peptide bond prolactin, yielding - upon reduction intramolecular disulfide bonds fragment. This inhibited basic fibroblast growth factor (FGF)-induced endothelial cell proliferation vitro. site highly conserved, both rat were this either species. Conversion to lysates was completely abolished MMP inhibitors EDTA, GM6001 or 1,10-phenanthroline. Purified MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 MMP-13 Gln157, one residue downstream protease cleavage site, following relative potency: MMP-8>MMP-13 >MMP-3>MMP-1=MMP-2>MMP-9. Finally, expressed mRNA (as revealed RT-PCR) they contained released (detected western blot proliferation). These results suggest several cartilage systemically derived locally