Articular cartilage superficial zone protein (SZP) is homologous to megakaryocyte stimulating factor precursor and is a multifunctional proteoglycan with potential growth-promoting, cytoprotective, and lubricating propertiesin cartilage metabolism

We have performed cDNA sequencing and homology analyses to elucidate the co mplete amino acid composition for a superficial zone protein (SZP) from hum an and bovine cartilage which has previously been shown to be a proteoglyca n specifically synthesized by chondrocytes located at the surface of bovine articular cartilage and also some synovial lining cells. The results of th is study indicate that cartilage SZP is homologous with a glycoprotein firs t described as the precursor protein of a megakaryocyte stimulating factor (MSF). Sequence comparisons and analyses indicate that (i) the amino acid c omposition of SZP is highly conserved between bovine and human species, (ii ) SZP contains structural motifs at the N- and C-termini which are similar to those found in vitronectin and which may impart cell-proliferative and m atrix-binding properties to the molecule, and (iii) SZP contains large and small mucin-like repeat domains composed of the sequences KEPAPTTT/P (76-78 repeats) and XXTTTX (6-8 repeats), respectively, which occur within a larg e central region of similar to 940 amino acids. The mucin-like domains are likely to be substituted with O-linked oligosaccharides which would impart lubricating properties to SZP which in part accumulates at the articular ca rtilage-synovial fluid interface. Additionally, we have shown that interleu kin-l inhibits the biosynthesis of chondrocyte SZP, while TGF-beta and IGF- 1 increase its biosynthesis, and that in pathological (osteoarthritic) huma n articular cartilage SZP mRNA can be expressed as an alternatively spliced variant lacking exons 4 and 5 which encode a potential heparin binding dom ain, The occurrence of different SZP alternative splice variants and the di fferential expression of SZP in the presence of cytokines and growth factor s suggest that SZP may play an important cytoprotective role by preventing cellular adhesion to the articular cartilage surface in normal cartilage me tabolism. Modifications to the structure of SZP, coupled with inhibition of SZP synthesis during inflammation, may account for the attachment and inva sion of pannus observed in inflammatory joint diseases, (C) 1999 Academic P ress.