Abstract
The aim of this study was to extend our earlier observations on the changes that occur in the proteoglycans (PGs) of discs subjected to experimental injury to the annulus fibrosus (AF). We employed the alginate bead culture method to examine the metabolism of the dermatan sulphate (DS) containing PGs by cells derived from different regions of ovine discs that had been subjected to experimental annular injury. This was compared with the metabolism of the DS-PGs by cells isolated from equivalent regions of normal sham-operated discs. Six months after induction of the annular lesion, AF cells isolated from the lesion produced significantly higher levels of decorin and biglycan in alginate bead culture than did cells from equivalent zones of the controls. Decorin and biglycan were identified in culture media samples by immunoblotting, using specific antibodies (6-B-6, LF-96), and also by positive identification of their de-glycosylated core proteins. The core protein of the DS-PGs has been shown to inhibit type I/II collagen fibrillogenesis, to negatively regulate the action of transforming growth factor-β (TGF-β) and to diminish cellular proliferation in vitro; events which may be detrimental to tissue repair. The findings are therefore consistent with our previous observation the annular lesions in the avascular inner annulus have no capacity to heal.
Similar content being viewed by others
References
Asundi V, Cowan K, Matzura D, Wagner W, Dreher KL (1990) The characterisation of extracellular matrix proteoglycan transcripts expressed by vascular smooth muscle cells. Eur J Cell Biol 52:98–104
Bianco P, Fisher LW, Young MF, Termine JD, Gehron Robey P (1990) Expression and localisation of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues. J Histochem Cytochem 38:1549–1563
Border WA, Okuda S, Languino LR, Ruoslahti E (1990) Transforming growth factor beta regulates production of proteoglycans by mesangial cells. Kidney Int 37:689–695
Brown DC, Vogel KG (1989) Characteristics of the in-vitro interaction of a small proteoglycan (PGII) of bovine tendon with type I collagen. Matrix 9: 468–478
Buckwalter JA (1995) Spine update. Ageing and degeneration of the human intervertebral disc. Spine 20:1307–1314
Butler WF (1988) Comparative anatomy and development of the mammalian disc. In: Ghosh P (ed) The biology of the intervertebral disc, vol. 1. CRC Press, Boca Raton, pp 39–82
Chelburg MK, Banks GM, Geiger DF, Oegema TR (1995) Identification of heterogeneous cell populations in normal human intervertebral discs. J Anat 186:43–53
Collier S, Ghosh P (1996) Effects of transforming growth factor beta on proteoglycan synthesis by cell and explant cultures derived from knee joint meniscus. Osteoarthritis Cartilage 3: 127–138
Collier S, Ghosh P (1996) Healing of circular defects in the rabbit medial meniscus can occur spontaneously and is not improved by intra articular hyaluronic acid. Vet Comp Orthop Traumatol 9:60–65
Fedarko NS, Vetter UK, Weinstein S, Gehron-Robey P (1992) Age related changes in hyaluronic acid, proteoglycan, collagen and osteonectin synthesis by human bone cells. J Cell Physiol 151:215–227
Fisher L, Termine JD, Young MF (1989) Deduced protein sequence of bone small proteoglycan-I (biglycan) shows homology with proteoglycan-II (decorin) and several non-connective tissue proteins in a variety of species. J Biol Chem 264:4571–4576
Fisher LW, Stubbs JT, Young MF (1995) Antisera and cDNA probes to human and certain animal model bone matrix noncollagenous proteins. Acta Orthop Scand [Suppl 266] 66:61–65
Gesink DS, Kitabayashi LR, Massie JB, Amiel D, Woods VL, Akeson WH (1994) Integrin expression in injured intervertebral discs of rabbits. Trans Orthop Res Soc 19:90
Hampton D, Laros G, McCarron R, Frank D (1989) Healing potential of the annulus fibrosus. Spine 14:398–401
Hilton RC, Ball J (1984) Vertebral rim lesions in the dorsolumbar spine. Ann Rheum Dis 43:302–307
Jarvelainen HT, Kinsella MG, Wight TN, Sandell LJ (1991) Differential expression of small chondroitin dermatan sulphate proteoglycans PG-I/biglycan, PG-II/decorin by vascular smooth muscle cells and endothelial cells in culture. J Biol Chem 266: 23 274–23 281
Kääpa E, Holm S, Han X, Takala T, Kovanen V, Vanharanta H (1994) Collagens in the injured porcine intervertebral disc. J Orthop Res 12:93–102
Kääpa E, Holm S, Inkinen R, Lammi M, Tammi M, Vanharanta H (1994) Proteoglycan chemistry in experimentally injured porcine intervertebral discs. J Spinal Disord 7:296–306
Kääpa E, Zhang L-Q, Holm S, Muona P, Vanharanta H (1994) Expression of type I, III, and VI mRNAs in experimentally injured porcine intervertebral disc. Connect Tissue Res 30: 203–214
Kääpa E, Han X, Holm S, Peltonen J, Takala T, Vanharanta H (1995) Collagen synthesis and types I, III, IV, and VI collagens in an animal model of disc degeneration. Spine 20:59–67
Kahari VM, Larjava H, Uitto J (1991) Differential regulation of extracellular matrix proteoglycan gene expression: TGF-β1 upregulates biglycan PG-I and versican (large fibroblast proteoglycan) but down regulates decorin (PG-II) mRNA levels in human fibroblasts in culture. J Biol Chem 266: 10608–10615
Krull NB, Zimmermann T, Gressner AM (1993) Spatial and temporal patterns of gene expression for the proteoglycans biglycan and decorin and for TGF-β1 revealed by in-situ hybridisation during experimental induced liver fibrosis in the rat. Hepatology 18: 581–589
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Latham JM, Pearcy MJ, Costi JJ, Moore R, Fraser RD, Vernon-Roberts B (1994) Mechanical consequences of annular tears and subsequent intervertebral disc degeneration. Clin Biomech 9:211–219
Lynch SE, Nixon JC, Colvin RB, Antoniades HN (1987) Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. Proc Natl Acad Sci (USA) 84:7696–7700
Maldonado BA, Oegama TR (1992) Initial characterisation of the metabolism of intervertebral disc cells encapsulated in microspheres. J Orthop Res 10:677–690
Melrose J, Ghosh P, Taylor TKF (1994) Proteoglycan heterogeneity in the normal adult ovine intervertebral disc. Matrix 14:61–75
Melrose J, Ghosh P, Taylor TKF, Hall A, Osti OL, Vernon-Roberts B, Fraser RD (1992) A longitudinal study of the matrix changes induced in the intervertebral disc by surgical damage to the annulus fibrosus. J Orthop Res 10: 665–676
Melrose J, Ghosh P, Taylor TKF, Latham J, Moore R (1997) Topographical variation in the catabolism of aggrecan in an ovine annular lesion model of experimental disc degeneration. J Spinal Disord 10: 55–67
Moore RJ, Vernon-Roberts B, Osti OL, Fraser RD (1996) Remodelling of vertebral bone after outer annular injury. Spine 21:936–940
Nakamura T, Miller D, Ruoslahti E, Border WA (1992) Production of extracellular matrix by glomerular epithelial cells is regulated by transforming growth factor-β1. Kidney Int 41:1213–1221
Oegema TR (1993) Biochemistry of the intervertebral disc. Clin Sports Med 12:419–439
Okuda S, Languino LR, Ruoslahti E, Border WA (1990) Elevated expression of TGF-β and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix. J Clin Invest 86:453–462
Osti OL, Vernon-Roberts B, Fraser RD (1990) Annulus tears and intervertebral disc degeneration. An experimental study using an animal model. Spine 15:762–767
Osti OL, Vernon-Roberts B, Moore R, et al (1992) Annular tears and disc degeneration in the human lumbar spine: a post-mortem study of 135 discs. J Bone Joint Surg [Br] 74:678–682
Pearce RH (1992) Morphologic and chemical aspects of ageing. In: Buckwalter JA, Goldberg VM, Woo SL-Y (eds) Musculoskeletal soft-tissue ageing: impact on mobility. American Academy of Orthoepedic Surgeons Publication, Oak Ridge, Illinois, pp 363–379
Pierce GF, Mustoe TA, Lingelbach J, Masakowski VR, Griffin GL, Senior RM, Dueul TF (1989) Platelet derived growth factor and transforming growth factor-β enhance tissue repair activities by unique mechanisms. J Cell Biol 109: 429–440
Raines EW, Lane TF, Iruela-Arispe ML, Ross R, Sage EH (1992) The extracellular glycoprotein SPARC interacts with platelet derived growth factor (PDGF) AB and BB and inhibits the binding of PDGF to its receptors. Proc Natl Acad Sci (USA) 89:1281–1285
Ramasamy S, Lipke DW, McClain CJ, Hennig B (1995) Tumor necrosis factor reduces proteoglycan synthesis in cultured endothelial cells. J Cell Physiol 162:119–126
Riessen R, Isner JM, Blessing E, Loushin C, Nikol S, Wight TN (1994) Regional differences in the distribution of the proteoglycans biglycan and decorin in the extracellular matrix of atherosclerotic and restenotic human coronary arteries. Am J Pathol 144: 962–974
Romaris M, Heredia A, Molist A, Bassols AQ (1991) Differential effect of TGF-β on proteoglycan synthesis in human embryonic lung fibroblasts. Biochim Biophys Acta 1093:229–233
Roughley PJ, Melching LI, Recklies AD (1994) Changes in the expression of decorin and biglycan in human articular cartilage with age and regulation by TGF-β. Matrix Biol 14:51–59
Roughley PJ, White RJ (1992) The dermatan sulphate proteoglycans of the adult human meniscus. J Orthop Res 10:631–637
Ruoslahti E (1988) Structure and biology of proteoglycans. Ann Rev Cell Biol 4:229–255
Ruoslahti E, Yamaguchi Y (1991) Proteoglycans as modulators of growth factor activities. Cell 64: 867–869
Scholzen T, Solursh M, Suzuki S, Reiter R, Morgan J, Buchberg AM, Siracusa LD, Iozzo RV (1994) The murine decorin. Complete cDNA cloning, genomic organisation, chromosomal assignment and expression during organogenesis and tissue differentiation. J Biol Chem 269: 28 270–28 281
Sempowski GD, Borrello MA, Blieden TM, Barth RK, Phipps RP (1995) Fibroblast heterogeneity in the healing wound. Wound Rep Reg 3:120–131
Smith JW, Walmsley R (1951) Experimental incision of the intervertebral disc. J Bone Joint Surg [Br] 33: 612–625
Sobue M, Nakashima T, Nagasaka T, Kato T, Ogura T, Takeuchi J (1988) Production and characterisation of a monoclonal antibody to dermatan sulphate proteoglycan. J Histochem Cytochem 36:479–485
Stichel CC, Kappler J, Junghans U, Koops A, Kresse H, Müller HW (1995) Differential expression of the small chondroitin/dermatan sulfate proteoglycans decorin and biglycan after injury of the adult rat brain. Brain Res 704:263–274
Swann DA, Garg HG, Jung W, Hermann H (1985) Studies on human scar tissue proteoglycans. J Invest Dermatol 84:527–531
Thompson JP, Oegema TR, Bradford DS (1991) Stimulation of mature cranine intervertebral disc by growth factors. Spine 16:253–260
Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets. Procedure and some applications. Proc Natl Acad Sci (USA) 76:4350–4354
Ungefronen H, Ergun S, Krull NB, Holstein AF (1995) Expression of the small proteoglycans biglycan and decorin and in the adult human testis. Biol Reprod 52:1095–1105
Urban JPG, Roberts S (1995) Development and degeneration of the intervertebral disc. Mol Med Today 1: 329–335
Veness-Meehan KA, Rhodes DN, Stiles AD (1994) Temporal and spatial expression of biglycan in chronic oxygen induced lung injury. Am J Respir Cell Mol Biol 11: 509–516
Vernon-Roberts B (1988) Disc pathology and disease states. In: Ghosh P (ed) The biology of the intervertebral disc, vol. II. CRC Press, Boca Raton, pp 73–120
Vernon-Roberts B (1992a) Age related and degenerative pathology of intervertebral discs and apophyseal joints. In: Jayson MIV (ed) The lumbar spine and back pain, 4th edn. Churchill-Livingstone, Edinburgh, pp 17–41
Vernon-Roberts B (1992b) The normal ageing of the spine: degeneration and arthritis. In: Andersson GBJ, McNeill TW (eds) Lumbar spinal stenosis. Mosby Year Book, St. Louis, pp 57–75
Vernon-Roberts B, Pirie CJ (1977) Degenerative changes in the intervertebral discs of the lumbar spine and their sequelae. Rheum Rehabil 16:13–21
Westergren-Thorson G, Antonsson P, Malmström A, Heinegård D, Oldberg A (1991) The synthesis of a family of structurally related proteoglycans in fibroblasts is differently regulated by TGF-β. Matrix 11: 177–183
Westergren-Thorsson G, Hernnäs J, Särnstrand B, Oldberg A, Heinegård D, Malmström A (1993) Altered expression of small proteoglycans, collagen and TGF-β1 in developing bleomycin and induced pulmonary fibrosis in rats. J Clin Invest 92:632–637
Yamaguchi Y, Mann D, Ruoslahti E (1990) Negative regulation of transforming growth factor beta by the proteoglycan decorin. Nature 346: 281–282
Yeo T-K, Brown L, Dvorak HF (1991) Alterations in proteoglycan synthesis common to healing wounds and tumors. Am J Pathol 138:1437–1450
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Melrose, J., Ghosh, P., Taylor, T.K.F. et al. Elevated synthesis of biglycan and decorin in an ovine annular lesion model of experimental disc degeneration. Eur Spine J 6, 376–384 (1997). https://doi.org/10.1007/BF01834063
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01834063