Proteoglycans and Diseases of Soft Tissues

  • Jaroslava HalperEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 802)


Proteoglycans consist of a protein core to which at least one glycosaminoglycan chain is attached. They play important roles in the physiology and biomechanical function of tendons, ligaments and cardiovascular system through their involvement in regulation of assembly and maintenance of extracellular matrix, and as they participate in cell proliferation through their interactions with growth factors. They can be divided into two main groups of small and large proteoglycans. The small proteoglycans are also known as small leucine-rich proteoglycans (or SLRPs) which are encoded by 17 genes and are further subclassified into Classes I–V. Several members of Class I and II, such as decorin and biglycan from Class I, and Class II fibromodulin and lumican, are known to regulate collagen fibrillogenesis. Decorin limits the diameter of collagen fibrils during fibrillogenesis. The function of biglycan in fibrillogenesis is similar to that of decorin. Though biomechanical function of tendon is compromised in decorin-deficient mice, decorin can substitute for lack of biglycan in biglycan-deficient mice. New data also indicate an important role for biglycan in disorders of the cardiovascular system, including aortic valve stenosis and aortic dissection. Two members of the Class II of SLRPs, fibromodulin and lumican bind to the same site within the collagen molecule and can substitute for each other in fibromodulin- or lumican-deficient mice.

Aggrecan and versican are the major representatives of the large proteoglycans. Though they are mainly found in the cartilage where they provide resilience and toughness, they are also present in tensile portions of tendons and, in slightly different biochemical form in fibrocartilage. Degradation with aggrecanase is responsible for the appearance of different forms of aggrecan and versican in different parts of the tendon where these cleaved forms play different roles. In addition, they are important components of the ventricularis of cardiac valves. Mutations in the gene for versican or in the gene for elastin (which binds to versican) lead to severe disruptions of normal developmental of the heart at least in mice.


Small leucine-rich proteoglycans (SLRPs) Collagen fibrillogenesis Aggrecan Versican Heart development 


  1. 1.
    Yoon JH, Halper J (2005) Tendon proteoglycans: biochemistry and function. J Musculoskelet Neuronal Interact 5:22–34PubMedGoogle Scholar
  2. 2.
    Iozzo RV (1998) Matrix proteoglycans: from molecular design to cellular function. Annu Rev Biochem 67:609–652PubMedCrossRefGoogle Scholar
  3. 3.
    Carter DR, Beaupré GS (eds) (2007) Skeletal function and form. Cambridge University Press, CambridgeGoogle Scholar
  4. 4.
    Vogel KS, Sandy JD, Pogány G, Robbins JR (1994) Aggrecan in bovine tendon. Matrix Biol 14:171–179PubMedCrossRefGoogle Scholar
  5. 5.
    Samiric T, Parkinson J, Ilic MZ, Cook J, Feller JA, Handley CJ (2009) Changes in the composition of the extracellular matrix in patellar tendinopathy. Matrix Biol 28:230–236PubMedCrossRefGoogle Scholar
  6. 6.
    Engel MB, Zerlotti E (1967) Changes in cells, matrix and water of calcifying turkey leg tendons. Am J Anat 120:489–525PubMedCrossRefGoogle Scholar
  7. 7.
    Spiesz EM, Roschger P, Zysset PK (2012) Influence of mineralization and microporosity on tissue elasticity: experimental and numerical investigation on mineralized turkey leg tendons. Calcif Tissue Int 90:319–329PubMedCrossRefGoogle Scholar
  8. 8.
    Manning PL, Morris PM, McMahon A, Jones E, Gize A, Macquaker JH, Wolff G, Thompson A, Marshall J, Taylor KG, Lyson T, Gaskell S, Reamtong O, Sellers WI, van Dongen BE, Buckley M, Wogelius RA (2009) Mineralized soft-tissue structure and chemistry in a mummified hadrosaur from the Hell Creek Formation, North Dakota (USA). Proc Biol Sci 276:3429–3437PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Berenson MC, Blevins FT, Plaas AH, Vogel KG (1996) Proteoglycans of human rotator cuff tendons. J Orthop Res 14:518–525PubMedCrossRefGoogle Scholar
  10. 10.
    Parkinson J, Samiric T, Ilic MZ, Cook J, Handley CJ (2011) Involvement of proteoglycans in tendinopathy. J Musculoskelet Neuronal Interact 11:86–93PubMedGoogle Scholar
  11. 11.
    Iozzo RV (2007) The family of the small leucine-rich proteoglycans: key regulators of matrix assembly and cellular growth. Mol Biol Cell 32:141–174Google Scholar
  12. 12.
    Iozzo RV, Schaefer L (2010) Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine-rich proteoglycans. FEBS J 277:3864–3875PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Iozzo RV (1999) The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins. J Biol Chem 274:18843–18846PubMedCrossRefGoogle Scholar
  14. 14.
    Iozzo RV, Murdoch AD (1996) Proteoglycans of the extracellular environment: clues from the gene and protein side offer novel perspectives in molecular diversity of function. FASEB J 10:598–614PubMedGoogle Scholar
  15. 15.
    Rada JA, Schrecengost PK, Hassell JR (1993) Regulation of corneal collagen fibrillogenesis in vitro by corneal proteoglycan (lumican and decorin) core protein. Exp Eye Res 56:635–648PubMedCrossRefGoogle Scholar
  16. 16.
    Schönherr E, Witsch-Prehm P, Harrach B, Robenek H, Rauterberg J, Kresse H (1995) Interaction of biglycan with type I collagen. J Biol Chem 270:2776–2783PubMedCrossRefGoogle Scholar
  17. 17.
    Schönherr E, Hausser E, Beavan L, Kresse H (1995) Decorin-type I collagen interaction. Presence of separate core protein-binding domains. J Biol Chem 270:8877–8883PubMedCrossRefGoogle Scholar
  18. 18.
    Svensson L, Närlid I, Oldberg Å (2000) Fibromodulin and lumican bind to the same region on collagen type I fibrils. FEBS Lett 470:178–182PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang G, Ezura Y, Chervoneva I, Robinson PS, Beason DP, Carine ET, Soslowsky LJ, Iozzo RV, Birk DE (2006) Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development. J Cell Biochem 98:1436–1449PubMedCrossRefGoogle Scholar
  20. 20.
    Schaefer L, Iozzo RV (2008) Biological functions of the small leucine-rich proteoglycans: from genetics to signal transduction. J Biol Chem 283:21305–21309PubMedCrossRefGoogle Scholar
  21. 21.
    McEwan PA, Scott PG, Bishop PN, Bella J (2006) Structural correlations in the family of small leucine-rich repeat proteins and proteoglycans. J Struct Biol 155:294–305PubMedCrossRefGoogle Scholar
  22. 22.
    Heinegård D (2009) Proteoglycans and more – from molecules to biology. Int J Exp Pathol 70:575–586CrossRefGoogle Scholar
  23. 23.
    Bengtsson E, Apberg A, Heinegård D, Sommarin Y, Spillmann D (2000) The amino-terminal part of PRELP binds to heparin and heparan sulfate. J Biol Chem 275:40695–40702PubMedCrossRefGoogle Scholar
  24. 24.
    Ohta K, Kuriyama S, Okafuji T, Gejima R, Ohnuma S, Tanaka H (2006) Tsukushi cooperates with VG1 to induce primitive streak and Hensen’s node formation in the chick embryo. Development 133:3777–3786PubMedCrossRefGoogle Scholar
  25. 25.
    Shimizu-Hirota R, Sasamura H, Kuroda M, Kobayashi E, Saruta T (2004) Functional characterization of podocan, a member of a new class in the small leucine-rich repeat protein family. FEBS Lett 563:69–74PubMedCrossRefGoogle Scholar
  26. 26.
    Bredrup C, Knappskog PM, Majewski J, Rødahl E, Boman H (2005) Congenital stromal dystrophy of the cornea caused by a mutation in the decorin gene. Invest Ophthalmol Vis Sci 46:420–426PubMedCrossRefGoogle Scholar
  27. 27.
    Bredrup C, Stang E, Bruland O, Palka BP, Young RD, Haavik J, Knappskog PM, Rødahl E (2010) Decorin accumulation contributes to the stromal opacities found in congenital stromal corneal dystrophy. Invest Ophthalmol Vis Sci 51:5578–5582PubMedCrossRefGoogle Scholar
  28. 28.
    Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, Iozzo RV (1997) Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol 136:729–743PubMedCrossRefGoogle Scholar
  29. 29.
    Reed CC, Iozzo RV (2003) The role of decorin in collagen fibrillogenesis and skin homeostasis. Glycoconj J 19:249–255CrossRefGoogle Scholar
  30. 30.
    Schönherr E, Broszat M, Brandan E, Bruckner P, Kresse H (1998) Decorin core protein fragment Leu155-Val260 interacts with TGF-beta but does not compete for decorin binding to type I collagen. Arch Biochem Biophys 355:241–248PubMedCrossRefGoogle Scholar
  31. 31.
    Santra M, Reed CC, Iozzo RV (2002) Decorin binds to a narrow region of the EGF receptor, partially overlapping with, but distinct from, the EGF-binding epitope. J Biol Chem 277:35671–35681PubMedCrossRefGoogle Scholar
  32. 32.
    Hildebrand A, Romaris M, Rasmussen IM, Heinegard D, Twardzik DR, Border WA, Ruoslahti E (1994) Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth beta. Biochem J 302:527–534PubMedGoogle Scholar
  33. 33.
    Tiedemann K, Olander B, Eklund E, Todorova L, Bengtsson M, Maccarana M, Westergren-Thorsson G, Malmström A (2005) Regulation of the chondroitin/dermatan fine structure by transforming growth factor-β1 through effects on polymer-modifying enzymes. Glycobiology 15:1277–1285PubMedCrossRefGoogle Scholar
  34. 34.
    Kuo CK, Petersen BC, Tuan RS (2008) Spatiotemporal protein distribution of TGFβs, their receptors, and extracellular matrix molecules during embryonic tendon development. Dev Dyn 237:1477–1489PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Dunkman AA, Buckley MR, Mienaltowski MJ, Adams SM, Thomas SJ, Satchell L, Kumar A, Pathmanathan L, Beason DP, Iozzo RV, Birk DE, Soslowsky LJ (2013) Decorin expression is important for age-related changes in tendon structure and mechanical properties. Matrix Biol 32:3–13PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Ameye L, Young MF (2002) Mice deficient in small leucine-rich proteoglycans: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases. Glycobiology 12(9):107R–116RPubMedCrossRefGoogle Scholar
  37. 37.
    Krusius T, Ruoslahti E (1986) Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA. Proc Natl Acad Sci U S A 83:7683–7687PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Heegaard AM, Corsi A, Danielsen CC, Nielsen KL, Jorgensen HL, Riminucci M, Young MF, Bianco P (2012) Biglycan deficiency causes spontaneous dissection and rupture in mice. Circulation 115:2731–2738CrossRefGoogle Scholar
  39. 39.
    Wiberg C, Heinegard D, Wenglen C, Timpl R, Morgelin M (2002) Biglycan organizes collagen VI into hexagonal-like networks resembling tissue structures. J Biol Chem 277:49120–49126PubMedCrossRefGoogle Scholar
  40. 40.
    Lechner BE, Lim JH, Mercado ML, Fallon JR (2006) Developmental regulation of biglycan expression in muscle and tendon. Muscle Nerve 34:347–355PubMedCrossRefGoogle Scholar
  41. 41.
    Rees SG, Dent CM, Caterson B (2009) Metabolism of proteoglycans in tendon. Scand J Med Sci Sports 19:470–478PubMedCrossRefGoogle Scholar
  42. 42.
    Corsi A, Xu T, Chen XD, Boyde A, Liang J, Mankani M, Summer B, Iozzo RV, Eichstetter I, Robey PG, Bianco P, Young MF (2002) Phenotypic effects of bioblycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues. J Bone Miner Res 17:1180–1189PubMedCrossRefGoogle Scholar
  43. 43.
    Ameye L et al (2002) Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis. FASEB J 16(7):673–680PubMedCrossRefGoogle Scholar
  44. 44.
    Young MF, Bi Y, Ameye L, Chen XD (2002) Biglycan knockout mice: new models for musculoskeletal diseases. Glycoconj J 19:257–262PubMedCrossRefGoogle Scholar
  45. 45.
    Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF (2007) Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med 13:1219–1227PubMedCrossRefGoogle Scholar
  46. 46.
    Bianco P, Fiaher LR, Young MF, Termine JD, Robey PG (1990) Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues. J Histochem Cytochem 38:1549–1563PubMedCrossRefGoogle Scholar
  47. 47.
    Yeo TK, Torok MA, Kraus HL, Evans SA, Zhou Y, Marcum JA (1995) Distribution of biglycan and its propeptide form in rat and bovine aortic tissue. J Vasc Res 32:175–182PubMedCrossRefGoogle Scholar
  48. 48.
    Song R, Zeng Q, Ao L, Yu JA, Cleveland JC, Zhao KS, Fullerton DA, Meng X (2012) Biglycan induces the expression of osteogenic factors in human aortic valve interstitial cells via Toll-like receptor-2. Arterioscler Thromb Vasc Biol 32:2711–2720PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Didangelos A, Mayr U, Monaco C, Mayr M (2012) Novel role of ADAMTS-5 protein in proteoglycan turnover and lipoprotein retention in atherosclerosis. J Biol Chem 287:19341–19345PubMedCrossRefGoogle Scholar
  50. 50.
    Coady MA, Davies RR, Roberts M, Goldstein LJ, Rogalski MJ, Rizzo JA, Hammond GL, Kopf GS, Elefteriades JA (1999) Familial patterns of thoracic aortic aneurysms. Arch Surg 134:361–367PubMedCrossRefGoogle Scholar
  51. 51.
    Lin AE, Lippe BM, Geffner ME, Gomes A, Lois JF, Barton CW, Rosenthal A, Friedman WF (1986) Aortic dilation, dissection, and rupture in patients with Turner syndrome. J Pediatr 109:820–826PubMedCrossRefGoogle Scholar
  52. 52.
    Kalamajski S, Aspberg A, Lindblom K, Heinegård D, Oldberg Ǻ (2009) Asporin competes with decorin for collagen binding, binds calcium and promotes osteoblast collagen mineralization. Biochem J 423:534–539CrossRefGoogle Scholar
  53. 53.
    Ikegawa S (2008) Expression, regulation and function of asporin, a susceptibility gene in common bone and joint diseases. Curr Med Chem 15:724–728PubMedCrossRefGoogle Scholar
  54. 54.
    Hedlund H, Mengarelli-Widholm S, Heinegård D, Reinholt FP, Svensson O (1994) Fibromodulin distribution and association with collagen. Matrix Biol 14:227–232PubMedCrossRefGoogle Scholar
  55. 55.
    Viola M (2007) Fibromodulin interactions with type I and II collagens. Connect Tissue Res 48:141–148PubMedCrossRefGoogle Scholar
  56. 56.
    Hedbom E, Heinegård D (1989) Interaction of a 59-dDa connective tissue matrix protein with collagen I and collagen II. J Biol Chem 264:6898–6905PubMedGoogle Scholar
  57. 57.
    Önnerfjord PH, Önnerfjord PH (2004) Identification of tyrosine sulfation in extracellular leucine-rich repeat proteins using mass spectrometry. J Biol Chem 279:26–33PubMedCrossRefGoogle Scholar
  58. 58.
    Chakravarti S, Magnuson T, Lass JH, Jepsen KJ, LaMantia C, Carroll H (1998) Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican. J Cell Biol 141:1277–1286PubMedCrossRefGoogle Scholar
  59. 59.
    Svensson L, Aszódi A, Reinholt FP, Fässler R, Heinegård D, Oldberg A (1999) Fibromodulin-null mice have abnormal collagen fibrils, tissue organization, and altered lumican deposition in tendon. J Biol Chem 274:9636–9647PubMedCrossRefGoogle Scholar
  60. 60.
    Jepsen KJ, Wu F, Peragallo JH, Paul J, Roberts L, Ezura Y, Oldberg Å, Birk DE, Chakravarti S (2002) A syndrome of joint laxity and impaired joint integrity in lumican- and fibromodulin-deficient mice. J Biol Chem 277:35532–35540PubMedCrossRefGoogle Scholar
  61. 61.
    Day JM, Olin AL, Murdoch AD, Canfield A, Sasaki T, Timpl R, Hardingham TE, Aspberg A (2004) Alternative splicing in the aggrecan G3 domain influences binding interactions with tenascin-C and other extracellular matrix proteins. J Biol Chem 279:12511–12518PubMedCrossRefGoogle Scholar
  62. 62.
    Stattin EL, Wiklund F, Lindblom K, Onnerfjord P, Jonsson BA, Tegner Y, Sasaki T, Struglics A, Lohmander S, Dahl N, Heinegård D, Aspberg A (2010) A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans. Am J Hum Genet 86:126–137PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Valhmu WB, Stazzone EJ, Bachrach NM, Saed-Nejad F, Fischer SG, Mow VC, Ratcliffe A (1998) Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression. Arch Biochem Biophys 353:29–36PubMedCrossRefGoogle Scholar
  64. 64.
    Ström A, Ahlqvist E, Heinegård D, Franzen A, Hultgårdh-Nilsson A (2004) Extracellular matrix components in atherosclerotic arteries of Apo E/LDL receptor deficient mice: an immunohistochemical study. Histol Histopathol 19:337–347PubMedGoogle Scholar
  65. 65.
    Munteanu SE, Ilic MZ, Handley CJ (2002) Highly sulfated glycosminoglycans inhibit aggrecanase degradation of aggrecan by bovine articular cartilage explant culture. Matrix Biol 21:429–440PubMedCrossRefGoogle Scholar
  66. 66.
    Rees SG, Flannery CR, Little CB, Hughes CE, Caterson B, Dent CM (2000) Catabolism of aggrecan, decorin and biglycan in tendon. Biochem J 350:181–188PubMedCrossRefGoogle Scholar
  67. 67.
    Tsuzaki M, Guyton G, Garrett W, Archambault JM, Herzog W, Almekinders L, Bynum D, Yang X, Banes AJ (2003) IL-1 beta induces COX2, MMP-1,-3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells. J Orthop Res 21:256–264PubMedCrossRefGoogle Scholar
  68. 68.
    Plaas A, Sandy JD, Liu H, Diaz MA, Schenkman D, Magnus RP, Bolam-Bretl C, Kopesky PW, Wang VM, Galante JO (2011) Biochemical identification and immunolocalization of aggrecan, ADAMTS5 and inter-alpha-trypsin-inhibitor in equine degenerative suspensory ligament desmitis. J Orthop Res 29:900–906PubMedCrossRefGoogle Scholar
  69. 69.
    Samiric T, Ilic MZ, Handley CJ (2004) Characterisation of proteoglycans and their catabolic products in tendon and explant cultures of tendon. Matrix Biol 23:127–140PubMedCrossRefGoogle Scholar
  70. 70.
    Wight T (2002) Versican: a versatile extracellular matrix proteoglycan in cell biology. Curr Opin Cell Biol 14:617–623PubMedCrossRefGoogle Scholar
  71. 71.
    Zhang Y, Cao L, Kiani C, Yang BL, Hu W, Yang B (1997) Promotion of chondrocyte proliferation by versican mediated by G1 domain and EGF-like motif. J Cell Biochem 73:445–457Google Scholar
  72. 72.
    Corps AN, Jones GC, Harrall RL, Curry VA, Hazleman BL, Riley GP (2008) The regulation of aggrecanase ADAMTS-4 expression in human Achilles tendon and tendon-derived cells. Matrix Biol 27:393–401PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Aspberg A, Adam S, Kostka G, Timpl R, Heinegård D (1999) Fibulin-1 is a ligand for the C-type lectin domains of aggrecan and versican. J Biol Chem 274:20444–20449PubMedCrossRefGoogle Scholar
  74. 74.
    Olin AI, Mörgelin M, Sasaki T, Timpl R, Heinegård D, Aspberg A (2001) The proteoglycans aggrecan and versican form networks with fibulin-2 through their lectin domain binding. J Biol Chem 276:1253–1261PubMedCrossRefGoogle Scholar
  75. 75.
    Wu YJ, Lapierre D, Wu J, Yee AJ, Yang BB (2005) The interaction of versican with its binding partners. Cell Res 15:483–494PubMedCrossRefGoogle Scholar
  76. 76.
    Choocheep K, Hatano S, Takagi H, Watanabe H, Kimata K, Kongtawelert P, Watanabe H (2010) Versican facilitates chondrocyte differentiation and regulates joint morphogenesis. J Biol Chem 285:21114–21125PubMedCrossRefGoogle Scholar
  77. 77.
    Hinton RBJ, Lincoln J, Deutsch GH, Osinska H, Manning PB, Benson DW, Yutzey KE (2006) Extracellular matrix remodeling and organization in developing and diseased aortic valves. Circ Res 98:1431–1438PubMedCrossRefGoogle Scholar
  78. 78.
    Lincoln J, Lange AW, Yutzey KE (2006) Hearts and bones: shared regulatory mechanisms in heart valve, cartilage, tendon, and bone development. Dev Biol 294:292–302PubMedCrossRefGoogle Scholar
  79. 79.
    Shelton EL, Yutzey KE (2008) Twist1 function in endocardial cushion cell proliferation, migration, and differentiation during heart valve development. Dev Biol 317:282–295PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Shelton EL, Yutzey KE (2007) Tbx20 regulation of endocardial cushion cell proliferation and extracellular matrix gene expression. Dev Biol 302:376–388PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Krishnamurthy VK, Opoka AM, Kern CB, Guilak F, Narmoneva DA, Hinton RB (2012) Maladaptive matrix remodeling and regional biomechanical dysfunction in a mouse model of aortic valve disease. Matrix Biol 31:197–205PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Visse MR, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839PubMedCrossRefGoogle Scholar
  83. 83.
    Mjaatvedt CH, Yamamura H, Capehart AA, Turner D, Markwald RR (1998) The Cspg2 gene, disrupted in the hdf mutant, is required for right cardiac chamber and endocardial cushion formation. Dev Biol 202:56–66PubMedCrossRefGoogle Scholar
  84. 84.
    Hatano S, Kimata K, Hiraiwa N, Kusakabe M, Isogai Z, Adachi E, Shinomura T, Watanabe H (2012) Versican/PG-M is essential for ventricular septal formation subsequent to cardiac atrioventricular cushion development. Glycobiology 22:1268–1277PubMedCrossRefGoogle Scholar
  85. 85.
    Huang R, Merrilees MJ, Braun K, Beaumont B, Lemire J, Clowes AW, Hinek A, Wight TN (2006) Inhibition of versican synthesis by antisense alters smooth muscle cell phenotype and induces elastic fiber formation in vitro and in neointima after vessel injury. Circ Res 98:370–377PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Department of Pathology, College of Veterinary Medicine and Medical PartnershipThe University of GeorgiaAthensUSA

Personalised recommendations