Lubricin

Lubricin is a large, water soluble glycoprotein encoded by the PRG4 gene. It has a molecular weight of 206,000 Daltons and consists of approximately equal proportions of protein and glycosaminoglycans. Electron microscope measurements show that the lubricin molecule is a partially extended flexible rod and, in solution, occupies a smaller spatial domain than would be expected from structural predictions.^[1] This characteristic may aid in the molecule's boundary lubricating ability.

Lubricin is present in synovial fluid and on the surface (superficial layer) of articular cartilage and therefore plays an important role in joint lubrication and synovial homeostasis. When first isolated, cartilage lubricin was called "superficial zone protein" (SZP).^[2] Human synovial fibroblasts have been shown to produce lubricin from the same gene responsible for megakaryocyte stimulating factor (MSF).^[3] Lubricin, MSF and SZP are now collectively known as Proteoglycan 4 (hence PRG4 for the gene nomenclature). The expression of lubricin has also been detected and the protein localised in tendon,^[4] meniscus,^[5] lung, liver, heart, bone,^[6] ligament, muscle and skin.^[7]

Lubricin, as MSF, was detected in the urine of patients undergoing bone marrow transplantation during a period of acute thrombocytopenia.^[8] Depletion of lubricin function has also been associated with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), an arthritis-like autosomal recessive disorder.^[9]

References

1. ^ Swann DA et al. (1981) The molecular structure of lubricating glycoprotein-I, the boundary lubricant for articular cartilage. J Biol Chem 256:5921-5925
2. ^ Jones AR et al.(2006) Binding and localisation of lubricin to articular cartilage surfaces. J Orthop Res Nov 14 epub
3. ^ Jay GD et al. (2000) Lubricin is a product of megakaryocyte stimulating factor gene expression by human synovial fibroblasts. J Rheumatol 27:594-600.
4. ^ Rees et al. (2002) Immunolocalisation and expression of proteoglycan 4 (cartilage superficial zone proteoglycan) in tendon Matrix Biol 21:593-602.
5. ^ Schumacher BL et al. (2005) Proteoglycan 4 (PRG4) synthesis and immunolocalization in bovine meniscus. J Orthop Res 23:562-568.
6. ^ Ikegawa S et al. (2000) Isolation, characterization and mapping of the mouse and human PRG4 (proteoglycan 4) genes. Cytogenet Cell Genet 90:291-297.
7. ^ Sun Y et al. (2006) Mapping lubricin in canine musculoskeletal tissues. Connect Tissue Res 47:215-221.
8. ^ Merberg DM et al. (1993) Comparison of vitronectin and megakaryocyte stimulating factor. In Biology of Vitronectins and their Receptors. (Preissner et al., eds) pp45-52 (Elsevier Science, Amsterdam).
9. ^ Marcelino J et al. (1999) PRG4, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Nat Genet 23:319-322.