Gene Symbol: Prg4
Description: proteoglycan 4 (megakaryocyte stimulating factor, articular superficial zone protein)
Alias: CACP, DOL54, JCAP, MSF, SZP, lubricin, proteoglycan 4, megakaryocyte-stimulating factor, proteoglycan 3, superficial zone proteoglycan
Species: mouse
Products:     Prg4

Top Publications

  1. Waller K, Zhang L, Elsaid K, Fleming B, Warman M, Jay G. Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis. Proc Natl Acad Sci U S A. 2013;110:5852-7 pubmed publisher
    ..b>Lubricin, a mucinous glycoprotein encoded by the PRG4 gene, provides boundary lubrication in articular joints...
  2. Rhee D, Marcelino J, Baker M, Gong Y, Smits P, Lefebvre V, et al. The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. J Clin Invest. 2005;115:622-31 pubmed
    ..Loss-of-function mutations in lubricin (a secreted glycoprotein encoded by the gene PRG4) cause the human autosomal recessive disorder camptodactyly-..
  3. Kohrs R, Zhao C, Sun Y, Jay G, Zhang L, Warman M, et al. Tendon fascicle gliding in wild type, heterozygous, and lubricin knockout mice. J Orthop Res. 2011;29:384-9 pubmed publisher
    The objective of this study was to investigate the role of lubricin in the lubrication of tendon fascicles...
  4. Jay G, Torres J, Rhee D, Helminen H, Hytinnen M, Cha C, et al. Association between friction and wear in diarthrodial joints lacking lubricin. Arthritis Rheum. 2007;56:3662-9 pubmed
    The glycoprotein lubricin (encoded by the gene Prg4) is secreted by surface chondrocytes and synovial cells, and has been shown to reduce friction in vitro...
  5. Ikegawa S, Sano M, Koshizuka Y, Nakamura Y. Isolation, characterization and mapping of the mouse and human PRG4 (proteoglycan 4) genes. Cytogenet Cell Genet. 2000;90:291-7 pubmed
    PRG4 (proteoglycan 4) has been identified as megakaryocyte stimulating factor and articular superficial zone protein...
  6. Taniguchi N, Caramés B, Ronfani L, Ulmer U, Komiya S, Bianchi M, et al. Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis. Proc Natl Acad Sci U S A. 2009;106:1181-6 pubmed publisher
    ..Aging is associated with a loss of HMGB2 expression and reduced cellularity, and this contributes to the development of OA. ..
  7. Novince C, Michalski M, Koh A, Sinder B, Entezami P, Eber M, et al. Proteoglycan 4: a dynamic regulator of skeletogenesis and parathyroid hormone skeletal anabolism. J Bone Miner Res. 2012;27:11-25 pubmed publisher
    b>Proteoglycan 4 (Prg4), known for its lubricating and protective actions in joints, is a strong candidate regulator of skeletal homeostasis and parathyroid hormone (PTH) anabolism. Prg4 is a PTH-responsive gene in bone and liver...
  8. Abusara Z, Krawetz R, Steele B, DuVall M, Schmidt T, Herzog W. Muscular loading of joints triggers cellular secretion of PRG4 into the joint fluid. J Biomech. 2013;46:1225-30 pubmed publisher
    ..testing system that allows quantification of joint loading and permits analysis of changes in total protein and PRG4 contents in joint fluid of intact knees in live mice...
  9. Hayashi M, Zhao C, Thoreson A, Chikenji T, Jay G, An K, et al. The effect of lubricin on the gliding resistance of mouse intrasynovial tendon. PLoS ONE. 2013;8:e83836 pubmed publisher
    The purpose of this study was to investigate the role of lubricin on the gliding resistance of intrasynovial tendons by comparing lubricin knockout, heterozygous, and wild type mice...

More Information


  1. Teeple E, Aslani K, Shalvoy M, Medrano J, Zhang L, Machan J, et al. Lubricin deficiency in the murine lumbar intervertebral disc results in elevated torsional apparent modulus. J Biomech. 2015;48:2210-3 pubmed publisher
    The purpose of this study was to investigate the mechanical consequences of proteoglycan 4 (Prg4) deficiency on intervertebral disc mechanics using a Prg4 knockout mouse model...
  2. Iwamoto M, Tamamura Y, Koyama E, Komori T, Takeshita N, Williams J, et al. Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis. Dev Biol. 2007;305:40-51 pubmed
    ..The results suggest that ERG is part of molecular mechanisms leading chondrocytes into a permanent developmental path and become joint forming cells, and may do so by acting downstream of GDF-5. ..
  3. Bechtold T, Saunders C, Decker R, Um H, Cottingham N, Salhab I, et al. Osteophyte formation and matrix mineralization in a TMJ osteoarthritis mouse model are associated with ectopic hedgehog signaling. Matrix Biol. 2016;52-54:339-354 pubmed publisher
    ..Here we report that Proteoglycan 4 (Prg4)-null TMJs exhibit irreversible osteoarthritis-like changes over time and are linked to formation of ..
  4. Alquraini A, Jamal M, Zhang L, Schmidt T, Jay G, Elsaid K. The autocrine role of proteoglycan-4 (PRG4) in modulating osteoarthritic synoviocyte proliferation and expression of matrix degrading enzymes. Arthritis Res Ther. 2017;19:89 pubmed publisher
    Lubricin/proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. Recently, we showed that recombinant human PRG4 (rhPRG4) is a putative ligand for CD44 receptor...
  5. Hill A, Waller K, Cui Y, Allen J, Smits P, Zhang L, et al. Lubricin restoration in a mouse model of congenital deficiency. Arthritis Rheumatol. 2015;67:3070-81 pubmed publisher
    Congenital deficiency of the principal boundary lubricant in cartilage (i.e., lubricin, encoded by the gene PRG4) increases joint friction and causes progressive joint failure...
  6. Koshizuka Y, Ikegawa S, Sano M, Nakamura K, Nakamura Y. Isolation of novel mouse genes associated with ectopic ossification by differential display method using ttw, a mouse model for ectopic ossification. Cytogenet Cell Genet. 2001;94:163-8 pubmed
    ..Our identification of the novel genes would give novel insight into the mechanism of ectopic ossification and etiology of OPLL. ..
  7. Shung C, Ota S, Zhou Z, Keene D, Hurlin P. Disruption of a Sox9-?-catenin circuit by mutant Fgfr3 in thanatophoric dysplasia type II. Hum Mol Genet. 2012;21:4628-44 pubmed publisher
  8. Hill A, Durán J, Purcell P. Lubricin protects the temporomandibular joint surfaces from degeneration. PLoS ONE. 2014;9:e106497 pubmed publisher
    ..The major component of synovial fluid is lubricin, a glycoprotein encoded by the gene proteoglycan 4 (Prg4), which is synthesized by chondrocytes at the surface of the articular cartilage and by synovial lining ..
  9. Swinehart I, Schlientz A, Quintanilla C, Mortlock D, Wellik D. Hox11 genes are required for regional patterning and integration of muscle, tendon and bone. Development. 2013;140:4574-82 pubmed publisher
    ..Thus, Hox genes are not simply regulators of skeletal morphology as previously thought, but are key factors that regulate regional patterning and integration of the musculoskeletal system. ..
  10. Kuroda M, Wang X, Sok J, Yin Y, Chung P, Giannotti J, et al. Induction of a secreted protein by the myxoid liposarcoma oncogene. Proc Natl Acad Sci U S A. 1999;96:5025-30 pubmed
    ..Here we report the isolation of a gene, DOL54, that is activated in primary fibroblasts by the expression of TLS-CHOP...
  11. Kuznetsov N, Sandblad L, Hase M, Hunziker A, Hergt M, Cordes V. The evolutionarily conserved single-copy gene for murine Tpr encodes one prevalent isoform in somatic cells and lacks paralogs in higher eukaryotes. Chromosoma. 2002;111:236-55 pubmed
    ..In summary, these results reveal Tpr to be a unique protein localized at the nuclear periphery of the somatic cell in mammals. ..
  12. Mundy C, Yasuda T, Kinumatsu T, Yamaguchi Y, Iwamoto M, Enomoto Iwamoto M, et al. Synovial joint formation requires local Ext1 expression and heparan sulfate production in developing mouse embryo limbs and spine. Dev Biol. 2011;351:70-81 pubmed publisher the Gdf5-Cre;Ext1(f/f) mutants, but contained an uneven articulating superficial zone that expressed very low lubricin levels...
  13. Novince C, Koh A, Michalski M, Marchesan J, Wang J, Jung Y, et al. Proteoglycan 4, a novel immunomodulatory factor, regulates parathyroid hormone actions on hematopoietic cells. Am J Pathol. 2011;179:2431-42 pubmed publisher
    b>Proteoglycan 4 (PRG4), a critical protective factor in articular joints, is implicated in hematopoietic progenitor cell expansion and megakaryopoiesis...
  14. Reuvers J, Thoreson A, Zhao C, Zhang L, Jay G, An K, et al. The mechanical properties of tail tendon fascicles from lubricin knockout, wild type and heterozygous mice. J Struct Biol. 2011;176:41-5 pubmed publisher
    The purpose of this study was to analyze the effects of lubricin on tendon stiffness and viscoelasticity...
  15. Gao Y, Lan Y, Liu H, Jiang R. The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation. Dev Biol. 2011;352:83-91 pubmed publisher
    ..In addition, joint cells in the double mutants failed to upregulate expression of the articular cartilage marker gene Prg4. These data indicate that Osr1 and Osr2 function redundantly to control synovial joint formation.
  16. Zhang M, Mani S, He Y, Hall A, Xu L, Li Y, et al. Induced superficial chondrocyte death reduces catabolic cartilage damage in murine posttraumatic osteoarthritis. J Clin Invest. 2016;126:2893-902 pubmed publisher
    ..These data imply that chondrocyte catabolism, not death, contributes to articular cartilage damage following injury. Therefore, therapies targeted at reducing the catabolic phenotype may protect against degenerative joint disease. ..
  17. Al Sharif A, Jamal M, Zhang L, Larson K, Schmidt T, Jay G, et al. Lubricin/Proteoglycan 4 Binding to CD44 Receptor: A Mechanism of the Suppression of Proinflammatory Cytokine-Induced Synoviocyte Proliferation by Lubricin. Arthritis Rheumatol. 2015;67:1503-13 pubmed publisher
    To evaluate the binding of recombinant human proteoglycan 4 (rhPRG4) to CD44 receptor and its consequences on cytokine-induced synoviocyte proliferation...
  18. Shibukawa Y, Young B, Wu C, Yamada S, Long F, Pacifici M, et al. Temporomandibular joint formation and condyle growth require Indian hedgehog signaling. Dev Dyn. 2007;236:426-34 pubmed
    ..This failure persisted at later stages, leading to complete absence of a normal functional disc and lubricin-expressing joint cavities...
  19. Koyama E, Yasuda T, Minugh Purvis N, Kinumatsu T, Yallowitz A, Wellik D, et al. Hox11 genes establish synovial joint organization and phylogenetic characteristics in developing mouse zeugopod skeletal elements. Development. 2010;137:3795-800 pubmed publisher
    ..In its place, an ulnar patella-like element developed that expressed lubricin on its ventral side facing the joint and was connected to the triceps muscle tendon...
  20. Schmidt T, Sullivan D, Knop E, Richards S, Knop N, Liu S, et al. Transcription, translation, and function of lubricin, a boundary lubricant, at the ocular surface. JAMA Ophthalmol. 2013;131:766-76 pubmed publisher
    ..To test the hypotheses that lubricin (ie, proteoglycan 4 [PRG4 ]), a boundary lubricant, is produced by ocular surface epithelia and acts to protect the cornea and ..
  21. Kozhemyakina E, Zhang M, Ionescu A, Ayturk U, Ono N, Kobayashi A, et al. Identification of a Prg4-expressing articular cartilage progenitor cell population in mice. Arthritis Rheumatol. 2015;67:1261-73 pubmed publisher
    To generate knockin mice that express a tamoxifen-inducible Cre recombinase from the Prg4 locus (Prg4(GFPCreERt2) mice) and to use these animals to fate-map the progeny of Prg4-positive articular cartilage cells at various ages...
  22. Waller K, Zhang L, Jay G. Friction-Induced Mitochondrial Dysregulation Contributes to Joint Deterioration in Prg4 Knockout Mice. Int J Mol Sci. 2017;18: pubmed publisher
    Deficiency of PRG4 (lubricin), the boundary lubricant in mammalian joints, contributes to increased joint friction accompanied by superficial and upper intermediate zone chondrocyte caspase-3 activation, as shown in lubricin-null (<..
  23. Coles J, Zhang L, Blum J, Warman M, Jay G, Guilak F, et al. Loss of cartilage structure, stiffness, and frictional properties in mice lacking PRG4. Arthritis Rheum. 2010;62:1666-74 pubmed publisher
    To assess the role of the glycoprotein PRG4 in joint lubrication and chondroprotection by measuring friction, stiffness, surface topography, and subsurface histology of the hip joints of Prg4(-/-) and wild-type (WT) mice...
  24. Kahn J, Shwartz Y, Blitz E, Krief S, Sharir A, Breitel D, et al. Muscle contraction is necessary to maintain joint progenitor cell fate. Dev Cell. 2009;16:734-43 pubmed publisher
    ..In conclusion, our findings provide the missing link between progenitor cell fate determination and embryonic movement, two processes shown to be essential for correct organogenesis. ..
  25. Ogawa H, Kozhemyakina E, Hung H, Grodzinsky A, Lassar A. Mechanical motion promotes expression of Prg4 in articular cartilage via multiple CREB-dependent, fluid flow shear stress-induced signaling pathways. Genes Dev. 2014;28:127-39 pubmed publisher
    b>Lubricin is a secreted proteoglycan encoded by the Prg4 locus that is abundantly expressed by superficial zone articular chondrocytes and has been noted to both be sensitive to mechanical loading and protect against the development of ..
  26. Bechtold T, Saunders C, Mundy C, Um H, Decker R, Salhab I, et al. Excess BMP Signaling in Heterotopic Cartilage Forming in Prg4-null TMJ Discs. J Dent Res. 2016;95:292-301 pubmed publisher
    ..Here, we show that aberrant chondrocyte differentiation and ectopic cartilage formation occur spontaneously in proteoglycan 4 (Prg4) mutant TMJ discs without further invasive procedure...
  27. Panagopoulos I, Mertens F, Isaksson M, Mandahl N. Expression of DOL54 is not restricted to myxoid liposarcomas with the FUS-DDIT3 chimera but is found in various sarcomas. Oncol Rep. 2004;12:107-10 pubmed
    The DOL54 gene [also known as megakaryocyte stimulating factor, articular superficial zone protein (SZP) or proteoglycan 4 (PRG4)], was cloned as a downstream target gene of the FUS-DDIT3 chimera, which is the fusion gene that ..
  28. Karamchedu N, Tofte J, Waller K, Zhang L, Patel T, Jay G. Superficial zone cellularity is deficient in mice lacking lubricin: a stereoscopic analysis. Arthritis Res Ther. 2016;18:64 pubmed publisher
    b>Lubricin, a mucinous glycoprotein secreted by synoviocytes and chondrocytes plays an important role in reducing the coefficient of friction in mammalian joints...
  29. Decker R, Um H, Dyment N, Cottingham N, Usami Y, Enomoto Iwamoto M, et al. Cell origin, volume and arrangement are drivers of articular cartilage formation, morphogenesis and response to injury in mouse limbs. Dev Biol. 2017;426:56-68 pubmed publisher
    ..Using novel Gdf5CreERT2 (Gdf5-CE), Prg4-CE and Dkk3-CE mice mated to R26-Confetti or single-color reporters, we found that knee joint progenitors produced ..