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)[4][5]. Lubricin, MSF, and SZP are now collectively known as Proteoglycan 4 (hence PRG4 for the gene nomenclature).The evidence that lubricin is actually a proteoglycan is not solid[6]. The expression of lubricin has also been detected and the protein localized in tendon,[7]meniscus,[8]lung, liver, heart, bone,[9]ligament, muscle, and skin.[10] It is present in human plasma, where it binds to neutrophils via L-selectin.[11]
Structure
The protein encoded by this gene is a approximately 345 kDa[12] specifically synthesized by chondrocytes located at the surface of articular cartilage, and also by synovial lining cells. The cDNA encodes a protein of 1,404 amino acids (human A isoform) with a somatomedin B homology domain, heparin-binding domains, multiple mucin-like repeats, a hemopexin domain, and an aggregation domain. There are 3 consensus sequences for N-glycosylation[3] and more than 168 sites for O-linked glycosylation[13]
Lubricin is a large glycoprotein that consists of approximately equal proportions of protein and oligosaccharides. The oligosaccharides are O-linked both with and without sialic acid..[11][13]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.[14] The large glycosylated region (i. e mucin domain) of lubricin makes it a water-soluble synovial fluid protein. In synovial fluid it interacts with Galectin-3 that improves its lubricating property.[15] Lubricins unglycosylated regions can interact cartilage proteins.[16][17] This characteristic may aid in the molecule's boundary lubricating ability.
The locus for autosomal recessive camptodactyly-arthropathy-coxa vara-pericarditis syndrome maps to chromosome 1q25-q31 where the PRG4 gene is located. Cell overgrowth may be primary to the pathogenesis of this protein.[3]
Lubricin’s role in improving tendon gliding has also been studied. While adding lubricin alone fails to affect the tendon gliding resistance, the addition of cd-gelatin plus lubricin significantly lowered the gliding resistance of the tendons. This research can aid in improving the gliding ability of tendon grafts done clinically.[19]Extracorporeal shockwave therapy application has been shown to induce an increased lubricin expression in tendons and septa of rat hindlimbs, which might suggest a beneficial lubricanting effect for joints and tissues prone to wear and tear degradation.[20]
References
↑ 1.01.1Marcelino J, Carpten JD, Suwairi WM, Gutierrez OM, Schwartz S, Robbins C, et al. (November 1999). "CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome". Nature Genetics. 23 (3): 319–22. doi:10.1038/15496. PMID10545950.
↑Flannery CR, Hughes CE, Schumacher BL, Tudor D, Aydelotte MB, Kuettner KE, Caterson B (January 1999). "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 properties in cartilage metabolism". Biochemical and Biophysical Research Communications. 254 (3): 535–41. doi:10.1006/bbrc.1998.0104. PMID9920774.
↑Schumacher BL, Block JA, Schmid TM, Aydelotte MB, Kuettner KE (May 1994). "A novel proteoglycan synthesized and secreted by chondrocytes of the superficial zone of articular cartilage". Archives of Biochemistry and Biophysics. 311 (1): 144–52. doi:10.1006/abbi.1994.1219. PMID8185311.
↑Jay GD, Britt DE, Cha CJ (March 2000). "Lubricin is a product of megakaryocyte stimulating factor gene expression by human synovial fibroblasts". The Journal of Rheumatology. 27 (3): 594–600. PMID10743795.
↑Lord MS, Estrella RP, Chuang CY, Youssef P, Karlsson NG, Flannery CR, Whitelock JM (2012). "Not all lubricin isoforms are substituted with a glycosaminoglycan chain". Connective Tissue Research. 53 (2): 132–41. doi:10.3109/03008207.2011.614364. PMID21966936.
↑Rees SG, Davies JR, Tudor D, Flannery CR, Hughes CE, Dent CM, Caterson B (November 2002). "Immunolocalisation and expression of proteoglycan 4 (cartilage superficial zone proteoglycan) in tendon". Matrix Biology. 21 (7): 593–602. doi:10.1016/S0945-053X(02)00056-2. PMID12475643.
↑Schumacher BL, Schmidt TA, Voegtline MS, Chen AC, Sah RL (May 2005). "Proteoglycan 4 (PRG4) synthesis and immunolocalization in bovine meniscus". Journal of Orthopaedic Research. 23 (3): 562–8. doi:10.1016/j.orthres.2004.11.011. PMID15885476..
↑Ikegawa S, Sano M, Koshizuka Y, Nakamura Y (2000). "Isolation, characterization and mapping of the mouse and human PRG4 (proteoglycan 4) genes". Cytogenetics and Cell Genetics. 90 (3–4): 291–7. doi:10.1159/000056791. PMID11124536.
↑Sun Y, Berger EJ, Zhao C, An KN, Amadio PC, Jay G (2006). "Mapping lubricin in canine musculoskeletal tissues". Connective Tissue Research. 47 (4): 215–21. doi:10.1080/03008200600846754. PMID16987753..
↑Su JL, Schumacher BL, Lindley KM, Soloveychik V, Burkhart W, Triantafillou JA, Kuettner K, Schmid T (June 2001). "Detection of superficial zone protein in human and animal body fluids by cross-species monoclonal antibodies specific to superficial zone protein". Hybridoma. 20 (3): 149–57. doi:10.1089/027245701750293475. PMID11461663.
↑Swann DA, Slayter HS, Silver FH (June 1981). "The molecular structure of lubricating glycoprotein-I, the boundary lubricant for articular cartilage". The Journal of Biological Chemistry. 256 (11): 5921–5. PMID7240180.
↑Flowers SA, Kalamajski S, Ali L, Björkman LI, Raj JR, Aspberg A, Karlsson NG, Jin C (September 2017). "Cartilage oligomeric matrix protein forms protein complexes with synovial lubricin via non-covalent and covalent interactions". Osteoarthritis and Cartilage. 25 (9): 1496–1504. doi:10.1016/j.joca.2017.03.016. PMID28373131.
↑Raj A, Wang M, Liu C, Ali L, Karlsson NG, Claesson PM, Dėdinaitė A (June 2017). "Molecular synergy in biolubrication: The role of cartilage oligomeric matrix protein (COMP) in surface-structuring of lubricin". Journal of Colloid and Interface Science. 495: 200–206. doi:10.1016/j.jcis.2017.02.007. PMID28208081.
↑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).
↑Taguchi M, Sun YL, Zhao C, Zobitz ME, Cha CJ, Jay GD, An KN, Amadio PC (January 2008). "Lubricin surface modification improves extrasynovial tendon gliding in a canine model in vitro". The Journal of Bone and Joint Surgery. American Volume. 90 (1): 129–35. doi:10.2106/JBJS.G.00045. PMID18171967.
↑Zhang D, Kearney CJ, Cheriyan T, Schmid TM, Spector M (November 2011). "Extracorporeal shockwave-induced expression of lubricin in tendons and septa". Cell and Tissue Research. 346 (2): 255–62. doi:10.1007/s00441-011-1258-7. PMID22009294.
Further reading
Bahabri SA, Suwairi WM, Laxer RM, Polinkovsky A, Dalaan AA, Warman ML (April 1998). "The camptodactyly-arthropathy-coxa vara-pericarditis syndrome: clinical features and genetic mapping to human chromosome 1". Arthritis and Rheumatism. 41 (4): 730–5. doi:10.1002/1529-0131(199804)41:4<730::AID-ART22>3.0.CO;2-Y. PMID9550484.
Morawietz L, Gehrke T, Frommelt L, Gratze P, Bosio A, Möller J, Gerstmayer B, Krenn V (July 2003). "Differential gene expression in the periprosthetic membrane: lubricin as a new possible pathogenetic factor in prosthesis loosening". Virchows Archiv. 443 (1): 57–66. doi:10.1007/s00428-003-0818-y. PMID12783322.
Liu YJ, Lu SH, Xu B, Yang RC, Ren Q, Liu B, Li B, Lu M, Yan FY, Han ZB, Han ZC (June 2004). "Hemangiopoietin, a novel human growth factor for the primitive cells of both hematopoietic and endothelial cell lineages". Blood. 103 (12): 4449–56. doi:10.1182/blood-2003-06-1825. PMID14976050.
de Haan G (February 2005). "A novel growth factor encoded by an old gene". Haematologica. 90 (2): 152. PMID15710563.
Rhee DK, Marcelino J, Al-Mayouf S, Schelling DK, Bartels CF, Cui Y, Laxer R, Goldbach-Mansky R, Warman ML (September 2005). "Consequences of disease-causing mutations on lubricin protein synthesis, secretion, and post-translational processing". The Journal of Biological Chemistry. 280 (35): 31325–32. doi:10.1074/jbc.M505401200. PMID16000300.
Alazami AM, Al-Mayouf SM, Wyngaard CA, Meyer B (February 2006). "Novel PRG4 mutations underlie CACP in Saudi families". Human Mutation. 27 (2): 213. doi:10.1002/humu.9399. PMID16429407.
Zhang D, Johnson LJ, Hsu HP, Spector M (July 2007). "Cartilaginous deposits in subchondral bone in regions of exposed bone in osteoarthritis of the human knee: histomorphometric study of PRG4 distribution in osteoarthritic cartilage". Journal of Orthopaedic Research. 25 (7): 873–83. doi:10.1002/jor.20344. PMID17343281.