Skip to main content

Advertisement

Log in

Targeted Disruption of Two Small Leucine-rich Proteoglycans, Biglycan and Decorin, Excerpts Divergent Effects on Enamel and Dentin Formation

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Small leucine-rich proteoglycans have been suggested to affect mineralization of dental hard tissues. To determine the functions of two of these small proteoglycans during the early stages of tooth formation, we characterized the dental phenotypes of biglycan (BGN KO) and decorin deficient (DCN KO) mice and compared them to that of wild type mice. Each targeted gene disruption resulted in specific effects on dentin and enamel formation. Dentin was hypomineralized in both knock out mice, although the effect was more prominent in the absence of decorin. Enamel formation was dramatically increased in newborn biglycan knockout mice but delayed in absence of decorin. Increased enamel formation in the former case resulted from an upregulation of amelogenin synthesis whereas delayed enamel formation in the later case was most probably an indirect consequence of the high porosity of the underlying dentin. Enamelin expression was unchanged in BGN KO, and reduced in DCN KO. Dentin sialoprotein (DSP), a member of the family of phosphorylated extracellular matrix proteins that play a role in dentinogenesis, was overexpressed in BGN-KO odontoblasts and in the sub-odontoblastic layer. In contrast, a decreased expression of DSP was detected in DCN KO. Dentin matrix protein-1 (DMP-1), bone sialoprotein (BSP) and osteopontin (OPN) were upregulated in BGN KO and downregulated in the DCN KO. Despite the strong effects induced by these deficiencies in newborn mice, no significant difference was detected between the three genotypes in adult mice, suggesting that the effects reported here in newborn mice are transient and subjected to self-repair.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Ruoslahti E (1988) Structure and biology of proteoglycans. Annu Rev Cell Biol 4:229–255

    Article  PubMed  CAS  Google Scholar 

  2. Iozzo RV, Murdoch AD (1996) Proteoglycans of the extracellular environment: clues from the gene and protein side offer novel perspectives in molecular diversity and function. FASEB J 10:598–614

    PubMed  CAS  Google Scholar 

  3. Embery G, Hall R, Waddington R, Septier D, Goldberg M (2001) Proteoglycans in dentinogenesis. Crit Rev Oral Biol Med 12:331–349

    Article  PubMed  CAS  Google Scholar 

  4. Fisher LW, Termine JD, Dejter SWJr, Whitson SW, Yanagishita M, Kimura JH, Hascall VC, Kleinman HK, Hassell JR, Nilsson B (1983) Proteoglycans of developing bone. J Biol Chem 258:6588–6594

    PubMed  CAS  Google Scholar 

  5. Cheng H, Caterson B, Neame PJ, Lester GE, Yamauchi M (1996) Differential distribution of lumican and fibromodulin in tooth cementum. Connect Tissue Res 34:87–96

    PubMed  CAS  Google Scholar 

  6. Baylink D, Wergedal J, Thompson E (1972) Loss of proteinpolysaccharides at sites where bone mineralization is initiated. J Histochem Cytochem 20:279–292

    PubMed  CAS  Google Scholar 

  7. Chen CC, Boskey AL. (1985) Mechanisms of proteoglycan inhibition of hydroxyapatite growth. Calcif Tissue Int 37:395–400

    PubMed  CAS  Google Scholar 

  8. Hunter GK (1991) Role of proteoglycan in the provisional calcification of cartilage. A review and reinterpretation. Clin Orthop 262:256–280

    PubMed  Google Scholar 

  9. Linde A, Bhown M, Butler WT (1980) Noncollagenous proteins of dentin. A re-examination of proteins from rat incisor dentin utilizing techniques to avoid artifacts. J Biol Chem 255:5931–5942

    PubMed  CAS  Google Scholar 

  10. Poole AR, Pidoux I, Rosenberg L (1982) Role of proteoglycans in endochondral ossification: immunofluorescent localization of link protein and proteoglycan monomer in bovine fetal epiphyseal growth plate. J Cell Biol 92:249–260

    Article  PubMed  CAS  Google Scholar 

  11. 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 12:107R–116R

    Article  PubMed  CAS  Google Scholar 

  12. Iozzo RV (1997) The family of the small leucine-rich proteoglycans: key regulators of matrix assembly and cellular growth. Crit Rev Biochem Mol Biol 32:141–174

    PubMed  CAS  Google Scholar 

  13. Iozzo RV (1999) The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins. J Biol Chem 274:18843–18846

    PubMed  CAS  Google Scholar 

  14. Neame PJ, Kay CJ, McQuillan DJ, Beales MP, Hassell JR (2000) Independent modulation of collagen fibrillogenesis by decorin and lumican. Cell Mol Life Sci 57:859–863

    PubMed  CAS  Google Scholar 

  15. Goldberg M, Takagi M (1993) Dentine proteoglycans: composition, ultrastructure and functions. Histochem J 25:781–806

    Article  PubMed  CAS  Google Scholar 

  16. Goldberg M, Septier D, Rapoport O, Young M, Ameye L (2002) Biglycan is a repressor of amelogenin expression and enamel formation: an emerging hypothesis. J Dent Res 81:520–524

    PubMed  CAS  Google Scholar 

  17. Matsuura T, Duarte WR, Cheng H, Uzawa K, Yamauchi M (2001) Differential expression of decorin and biglycan genes during mouse tooth development. Matrix Biol 20:367–373

    Article  PubMed  CAS  Google Scholar 

  18. Septier D, Hall RC, Embery G, Goldberg M (2001) Immunoelectron microscopic visualization of pro- and secreted forms of decorin and biglycan in the predentin and during dentin formation in the rat incisor. Calcif Tissue Int 69:38–45

    Article  PubMed  CAS  Google Scholar 

  19. Takagi M, Hishikawa H, Hosokawa Y, Kagami A, Rahemtulla F (1990) Immunohistochemical localization of glycosaminoglycans and proteoglycans in predentin and dentin of rat incisors. J Histochem Cytochem 38:319–324

    PubMed  CAS  Google Scholar 

  20. Wilda M, Bachner D, Just W, Geerkens C, Kraus P, Vogel W, Hameister H (2000) A comparison of the expression pattern of five genes of the family of small leucine-rich proteoglycans during mouse development. J Bone Miner Res 15:2187–2196

    PubMed  CAS  Google Scholar 

  21. Yoshiba N, Yoshiba K, Iwaku M, Ozawa H (1996) Immunolocalization of the small proteoglycan decorin in human teeth. Arch Oral Biol 41:351–357

    PubMed  CAS  Google Scholar 

  22. Chen XD, Shi S, Xu T, Robey PG, Young MF (2002) Age-related osteoporosis in biglycan-deficient mice is related to defects in bone marrow stromal cells. J Bone Miner Res 17:331–340

    PubMed  CAS  Google Scholar 

  23. 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 136:729–743

    Article  PubMed  CAS  Google Scholar 

  24. Xu T, Bianco P, Fisher LW, Longenecker G, Smith E, Goldstein S, Bonadio J, Boskey A, Heegaard AM, Sommer B, Satomura K, Dominguez P, Zhao C, Kulkarni AB, Robey PG, Young MF (1998) Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice. Nat Genet 20:78–82

    Article  PubMed  CAS  Google Scholar 

  25. Fisher LW, Stubbs JTIII, Young MF (1995) Antisera and cDNA probes to human and certain animal model bone matrix noncollagenous proteins. Acta Orthop Scand Suppl 266:61–65

    PubMed  CAS  Google Scholar 

  26. Gibson CW, Kucich U, Collier P, Shen G, Decker S, Bashir M, Rosenbloom J (1995) Analysis of amelogenin proteins using monospecific antibodies to defined sequences. Connect Tissue Res 32:109–114

    PubMed  CAS  Google Scholar 

  27. Dohi N, Murakami C, Tanabe T, Yamakoshi Y, Fukae M, Yamamoto Y, Wakida K, Shimizu M, Simmer JP, Kurihara H, UchidaT (1998) Immunocytochemical and immunochemical study of enamelins, using antibodies against porcine 89-kDa enamelin and its N-terminal synthetic peptide, in porcine tooth germs. Cell Tissue Res 293:313–325

    Article  PubMed  CAS  Google Scholar 

  28. Satchell PG, Anderton X, Ryu OH, Luan X, Ortega AJ, Opamen R, Berman BJ, Witherspoon DE, Gutmann JL, Yamane A, Zeichner-David M, Simmer JP, Shuler CF, Diekwisch TG (2002) Conservation and variation in enamel protein distribution during vertebrate tooth development. J Exp Zool 294:91–106

    Article  PubMed  CAS  Google Scholar 

  29. Goldberg M, Septier D (1996) A comparative study of the transition between predentin and dentin, using various preparative procedures in the rat. Eur J Oral Sci 104:269–277

    PubMed  CAS  Google Scholar 

  30. Ameye L, Aria D, Jepsen K, Oldberg A, Xu T, Young MF (2002) Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis. FASEB J 16:673–680

    Article  PubMed  CAS  Google Scholar 

  31. Corsi AT, Xu XD, Chen XD, Boyde A, Liang J, Mankani M, Sommer B, Iozzo RV, Eichstetter I, Robey PG, Bianco P, YoungMF (2002) Phenotypic effects of biglycan 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 17:1180–1189

    PubMed  CAS  Google Scholar 

  32. Fleischmajer R, Fisher LW, MacDonald ED, Jacobs, LJr, Perlish JS, Termine JD (1991) Decorin interacts with fibrillar collagen of embryonic and adult human skin. J Struct Biol 106:82–90

    Article  PubMed  CAS  Google Scholar 

  33. Gafni G, Septier D, Goldberg M (1999) Effect of chondroitin sulfate and biglycan on the crystallization of hydroxyapatite under physiological conditions. Journal of Crystal Growth 205:618–623

    Article  CAS  Google Scholar 

  34. Hocking AM, Shinomura T, McQuillan DJ (1998) Leucine-rich repeat glycoproteins of the extracellular matrix. Matrix Biol 17:1–19

    Article  PubMed  CAS  Google Scholar 

  35. Papagerakis P, MacDougall M, Hotton D, Bailleul-Forestier I, Oboeuf M, Berdal A (2003) Expression of amelogenin in odontoblasts. Bone 32:228–240

    Article  PubMed  CAS  Google Scholar 

  36. Schonherr E, Witsch-Prehm P, Harrach B, Robenek H, Rauterberg J, Kresse H (1995) Interaction of biglycan with type I collagen. J Biol Chem 270:2776–2783

    PubMed  CAS  Google Scholar 

  37. Scott JE, Dyne KM, Thomlinson AM, Ritchie M, Bateman J, Cetta G, M.Valli M (1998) Human cells unable to express decoron produced disorganized extracellular matrix lacking “shape modules” (interfibrillar proteoglycan bridges). Exp Cell Res 243:59–66

    Article  PubMed  CAS  Google Scholar 

  38. Veis A, Tompkins K, Alvares K, Wei K, Wang L, Wang XS, Brownell AG, Jengh SM, Healy KE (2000) Specific amelogenin gene splice products have signaling effects on cells in culture and in implants in vivo. J Biol Chem 275:41263–41272

    Article  PubMed  CAS  Google Scholar 

  39. Mitani Y, Honda A, Jasin HE (2001) Polymorphonuclear leukocyte adhesion to articular cartilage is inhibited by cartilage surface macromolecules. Rheumatol Int 20:180–185

    PubMed  CAS  Google Scholar 

  40. Fincham AG, Moradian-Oldak J, Simmer JP (1999) The structural biology of the developing dental enamel matrix. J Struct Biol 126:270–299

    Article  PubMed  CAS  Google Scholar 

  41. Kagayama M, Akita H, SasanoY (1995) Immunohistochemical localization of connexin 43 in the developing tooth germ of rat. Anat Embryol (Berl) 191:561–568

    CAS  Google Scholar 

  42. Kasper M, Karsten U, Stosiek P, Moll R (1989) Distribution of intermediate-filament proteins in the human enamel organ: unusually complex pattern of coexpression of cytokeratin polypeptides and vimentin. Differentiation 40:207–214

    PubMed  CAS  Google Scholar 

  43. Nishikawa S, Tsukita S, Tsukita S, Sasa S (1990) Localization of adherens junction proteins along the possible sliding interface between secretory ameloblasts of the rat incisor. Cell Struct Funct 15:245–249

    Article  PubMed  CAS  Google Scholar 

  44. Bianco P, Fisher LW, 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 38:1549–1563

    PubMed  CAS  Google Scholar 

  45. Kinsella MG, Tsoi CK, Jarvelainen HT, Wight TN (1997) Selective expression and processing of biglycan during migration of bovine aortic endothelial cells. The role of endogenous basic fibroblast growth factor. J Biol Chem 272:318–325

    PubMed  CAS  Google Scholar 

  46. Weber CK, Sommer G, Michl P, Fensterer H, Weimer M, Gansauge F, Leder G, Adler G, Gress TM (2001) Biglycan is overexpressed in pancreatic cancer and induces G1-arrest in pancreatic cancer cell lines. Gastroenterology 121:657–667

    Article  PubMed  CAS  Google Scholar 

  47. Moreno M, Munoz R, Aroca F, Labarca M, Brandan E, Larrain J (2005) Biglycan is a new extracellular component of the Chordin-BMP4 signaling pathway. EMBO J 24:1397–1405

    Article  PubMed  CAS  Google Scholar 

  48. Wiethoff CM, Smith JG, Koe GS, Middaugh CR (2001) The potential role of proteoglycans in cationic lipid-mediated gene delivery. Studies of the interaction of cationic lipid-DNA complexes with model glycosaminoglycans. J Biol Chem 276:32806–32813

    Article  PubMed  CAS  Google Scholar 

  49. Csordas G, Santra M, Reed CC, Eichstetter I, McQuillan DJ, Gross D, Nugent MA, Hajnoczky G, Iozzo RV (2000) Sustained down-regulation of the epidermal growth factor receptor by decorin. A mechanism for controlling tumor growth in vivo. J Biol Chem 275:32879–32887

    Article  PubMed  CAS  Google Scholar 

  50. Iozzo RV, Moscatello DK, McQuillan DJ, Eichstetter I (1999) Decorin is a biological ligand for the epidermal growth factor receptor. J Biol Chem 274:4489–4492

    PubMed  CAS  Google Scholar 

  51. Snead ML, Luo W, Lau EC, Slavkin HC (1988) Spatial- and temporal-restricted pattern for amelogenin gene expression during mouse molar tooth organogenesis. Development 104:77–85

    PubMed  CAS  Google Scholar 

  52. Wurtz T, Lundmark C, Christersson C, Bawden JW, Slaby I, Hammarstrom L (1996) Expression of amelogenin mRNA sequences during development of rat molars. J Bone Miner Res 11:125–131

    Article  PubMed  CAS  Google Scholar 

  53. InaiT, Kukita T, Ohsaki Y, Nagata K, Kukita A, Kurisu K (1991) Immunohistochemical demonstration of amelogenin penetration toward the dental pulp in the early stages of ameloblast development in rat molar tooth germs. Anat Rec 229:259–270

    Article  PubMed  CAS  Google Scholar 

  54. Nakamura M, Bringas P Jr, Nanci A, Zeichner-David M, Ashdown B, Slavkin HC (1994) Translocation of enamel proteins from inner enamel epithelia to odontoblasts during mouse tooth development. Anat Rec 238:383–396

    Article  PubMed  CAS  Google Scholar 

  55. SawadaT, Nanci A (1995) Spatial distribution of enamel proteins and fibronectin at early stages of rat incisor tooth formation. Arch Oral Biol 40:1029–1038

    Google Scholar 

  56. Beniash E, Traub W, Veis A, Weiner S (2000) A transmission electron microscope study using vitrified ice sections of predentin: structural changes in the dentin collagenous matrix prior to mineralization. J Struct Biol 132:212–225

    Article  PubMed  CAS  Google Scholar 

  57. Goldberg M, Septier D, Escaig-Haye F (1987) Glycoconjugates in dentinogenesis and dentine. Prog Histochem Cytochem 17:1–112

    PubMed  CAS  Google Scholar 

  58. Terasawa M, Shimokawa R, Terashima T, Ohya K, Takagi Y, Shimokawa H ((2004) Expression of dentin matrix protein 1 (DMP1) in nonmineralized tissues. J Bone Miner Metab 22:430–438

    Article  PubMed  CAS  Google Scholar 

  59. Ogbureke KU, Fisher LW (2004) Expression of SIBLINGs and their partener MMPs in salivary glands. J Dent Res 83:664–670

    PubMed  CAS  Google Scholar 

  60. Fisher LW, Jain A, Tayback M, Fedarko NS (2004) Small integrin binding ligand N-linked glycoprotein gene family expression in different cancers. Clin Cancer Res 15:8501–8511

    Google Scholar 

  61. Ogbureke KU, Fisher LW (2005) Renal expression of SIBLING proteins and their partner matrix metalloporteinases (MMPs). Kidney Int 68:155–166

    Article  PubMed  CAS  Google Scholar 

  62. Tartaix PH, Doulaverakis M, George A, Fisher LW, Butler WT, Qin C, Salih E, Tan M, Fujimoto Y, Spevak L, Boskey AL (2004) In vitro effects of dnetin matrix protein-1 on hydroxyapatite formation provide insights into in vivo functions. J Biol Chem 279:18115–18120

    Article  PubMed  CAS  Google Scholar 

  63. Boskey AL (1995) osteopontin and related phosphorylated sialoproteins: effects on mineralization. Ann N Y Acad Sci 21:249–256

    Google Scholar 

  64. Boskey A, Spevak L, Tan M, Doty SB, Butler WT (2000) Dentin sialoprotein (DSP) has limited effects on in vitro apatite formation and growth. Calcif Tissue Int 67:472–478

    Article  PubMed  CAS  Google Scholar 

  65. MacDougall M, Nydegger J, Gu TT, Simmons D, Luan X, Cavender A, D’Souza RN (1998) Developmental regulation of dnetin sialophosphoprotein during ameloblast differentiation: a potential enamel matrix nucleator. Connect Tissue Res 39:25–37

    PubMed  CAS  Google Scholar 

  66. Boskey AL, Muresca S, Doty S, Sabsay B, Veis A (1990) Concentration dependent effects od dentin phosphoryn in the regulation of in vitro hydroxyapatite formation and growth. Bone Mineral 11:55–65

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Karine Vidal for critical reading of the manuscript and Jennifer Clough for reviewing the English. We thanks also the Institute Benjamin Delessert for the grant kindly provided on “Proteoglycans and dental tissues”.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Goldberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Goldberg, M., Septier, D., Rapoport, O. et al. Targeted Disruption of Two Small Leucine-rich Proteoglycans, Biglycan and Decorin, Excerpts Divergent Effects on Enamel and Dentin Formation. Calcif Tissue Int 77, 297–310 (2005). https://doi.org/10.1007/s00223-005-0026-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-005-0026-7

Keywords

Navigation