• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Aug 15, 1996; 98(4): 996–1003.
PMCID: PMC507515

The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

Abstract

Very little is known about the turnover of extracellular matrix in the human intervertebral disc. We measured concentrations of specific molecules reflecting matrix synthesis and degradation in predetermined regions of 121 human lumbar intervertebral discs and correlated them with ageing and Thompson grade of degeneration. Synthesis in intervertebral discs, measured by immunoassay of the content of a putative aggrecan biosynthesis marker (846) and the content of types I and II procollagen markers, is highest in the neonatal and 2-5-yr age groups. The contents of these epitopes/molecules progressively diminished with increasing age. However, in the oldest age group (60-80 yr) and in highly degenerated discs, the type I procollagen epitope level increased significantly. The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II collagen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increasing age; however, it increased significantly in the oldest group and in highly degenerate discs. We identified three matrix turnover phases. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of type II collagen. Phase II (maturation and ageing) is distinguished by a progressive drop in synthetic activity and a progressive reduction in denaturation of type 11 collagen. Phase III (degeneration and fibrotic) is illustrated by evidence for a lack of increased synthesis of aggrecan and type II procollagen, but also by an increase in collagen type II denaturation and type I procollagen synthesis, both dependent on age and grade of tissue degeneration.

Full Text

The Full Text of this article is available as a PDF (251K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Holm S, Maroudas A, Urban JP, Selstam G, Nachemson A. Nutrition of the intervertebral disc: solute transport and metabolism. Connect Tissue Res. 1981;8(2):101–119. [PubMed]
  • Diamant B, Karlsson J, Nachemson A. Correlation between lactate levels and pH in discs of patients with lumbar rhizopathies. Experientia. 1968 Dec 15;24(12):1195–1196. [PubMed]
  • Nachemson A. Intradiscal measurements of pH in patients with lumbar rhizopathies. Acta Orthop Scand. 1969;40(1):23–42. [PubMed]
  • Oegema TR., Jr Biochemistry of the intervertebral disc. Clin Sports Med. 1993 Jul;12(3):419–439. [PubMed]
  • Buckwalter JA. Aging and degeneration of the human intervertebral disc. Spine (Phila Pa 1976) 1995 Jun 1;20(11):1307–1314. [PubMed]
  • Bradford DS, Oegema TR, Jr, Cooper KM, Wakano K, Chao EY. Chymopapain, chemonucleolysis, and nucleus pulposus regeneration. A biochemical and biomechanical study. Spine (Phila Pa 1976) 1984 Mar;9(2):135–147. [PubMed]
  • Garvin PJ, Jennings RB. Long-term effects of chymopapain on intervertebral disks of dogs. Clin Orthop Relat Res. 1973 May;(92):281–295. [PubMed]
  • Hadjipavlou A, Lander P, Antoniou J. The effect of chymopapain on low back pain. Orthop Rev. 1992 Jun;21(6):733–738. [PubMed]
  • Poole AR. Immunochemical markers of joint inflammation, skeletal damage and repair: where are we now? Ann Rheum Dis. 1994 Jan;53(1):3–5. [PMC free article] [PubMed]
  • Heinegård D, Saxne T. Molecular markers of processes in cartilage in joint disease. Br J Rheumatol. 1991;30 (Suppl 1):21–24. [PubMed]
  • Thonar EJ, Shinmei M, Lohmander LS. Body fluid markers of cartilage changes in osteoarthritis. Rheum Dis Clin North Am. 1993 Aug;19(3):635–657. [PubMed]
  • Hollander AP, Heathfield TF, Webber C, Iwata Y, Bourne R, Rorabeck C, Poole AR. Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay. J Clin Invest. 1994 Apr;93(4):1722–1732. [PMC free article] [PubMed]
  • Månsson B, Carey D, Alini M, Ionescu M, Rosenberg LC, Poole AR, Heinegård D, Saxne T. Cartilage and bone metabolism in rheumatoid arthritis. Differences between rapid and slow progression of disease identified by serum markers of cartilage metabolism. J Clin Invest. 1995 Mar;95(3):1071–1077. [PMC free article] [PubMed]
  • Antoniou J, Goudsouzian NM, Heathfield TF, Winterbottom N, Steffen T, Poole AR, Aebi M, Alini M. The human lumbar endplate. Evidence of changes in biosynthesis and denaturation of the extracellular matrix with growth, maturation, aging, and degeneration. Spine (Phila Pa 1976) 1996 May 15;21(10):1153–1161. [PubMed]
  • Caterson B, Christner JE, Baker JR, Couchman JR. Production and characterization of monoclonal antibodies directed against connective tissue proteoglycans. Fed Proc. 1985 Feb;44(2):386–393. [PubMed]
  • Rizkalla G, Reiner A, Bogoch E, Poole AR. Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence for molecular heterogeneity and extensive molecular changes in disease. J Clin Invest. 1992 Dec;90(6):2268–2277. [PMC free article] [PubMed]
  • Glant TT, Mikecz K, Roughley PJ, Buzás E, Poole AR. Age-related changes in protein-related epitopes of human articular-cartilage proteoglycans. Biochem J. 1986 May 15;236(1):71–75. [PMC free article] [PubMed]
  • Parfitt AM, Simon LS, Villanueva AR, Krane SM. Procollagen type I carboxy-terminal extension peptide in serum as a marker of collagen biosynthesis in bone. Correlation with Iliac bone formation rates and comparison with total alkaline phosphatase. J Bone Miner Res. 1987 Oct;2(5):427–436. [PubMed]
  • Prockop DJ, Kivirikko KI, Tuderman L, Guzman NA. The biosynthesis of collagen and its disorders (first of two parts). N Engl J Med. 1979 Jul 5;301(1):13–23. [PubMed]
  • Hinek A, Reiner A, Poole AR. The calcification of cartilage matrix in chondrocyte culture: studies of the C-propeptide of type II collagen (chondrocalcin). J Cell Biol. 1987 May;104(5):1435–1441. [PMC free article] [PubMed]
  • Dodge GR, Poole AR. Immunohistochemical detection and immunochemical analysis of type II collagen degradation in human normal, rheumatoid, and osteoarthritic articular cartilages and in explants of bovine articular cartilage cultured with interleukin 1. J Clin Invest. 1989 Feb;83(2):647–661. [PMC free article] [PubMed]
  • Thompson JP, Pearce RH, Schechter MT, Adams ME, Tsang IK, Bishop PB. Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc. Spine (Phila Pa 1976) 1990 May;15(5):411–415. [PubMed]
  • Alini M, Matsui Y, Dodge GR, Poole AR. The extracellular matrix of cartilage in the growth plate before and during calcification: changes in composition and degradation of type II collagen. Calcif Tissue Int. 1992 Apr;50(4):327–335. [PubMed]
  • Burleigh MC, Barrett AJ, Lazarus GS. Cathepsin B1. A lysosomal enzyme that degrades native collagen. Biochem J. 1974 Feb;137(2):387–398. [PMC free article] [PubMed]
  • Nimni ME. Collagen: structure, function, and metabolism in normal and fibrotic tissues. Semin Arthritis Rheum. 1983 Aug;13(1):1–86. [PubMed]
  • Farndale RW, Buttle DJ, Barrett AJ. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta. 1986 Sep 4;883(2):173–177. [PubMed]
  • Kempson GE, Muir H, Pollard C, Tuke M. The tensile properties of the cartilage of human femoral condyles related to the content of collagen and glycosaminoglycans. Biochim Biophys Acta. 1973 Feb 28;297(2):456–472. [PubMed]
  • Schmidt MB, Mow VC, Chun LE, Eyre DR. Effects of proteoglycan extraction on the tensile behavior of articular cartilage. J Orthop Res. 1990 May;8(3):353–363. [PubMed]
  • Aigner T, Bertling W, Stöss H, Weseloh G, von der Mark K. Independent expression of fibril-forming collagens I, II, and III in chondrocytes of human osteoarthritic cartilage. J Clin Invest. 1993 Mar;91(3):829–837. [PMC free article] [PubMed]
  • Hollander AP, Heathfield TF, Liu JJ, Pidoux I, Roughley PJ, Mort JS, Poole AR. Enhanced denaturation of the alpha (II) chains of type-II collagen in normal adult human intervertebral discs compared with femoral articular cartilage. J Orthop Res. 1996 Jan;14(1):61–66. [PubMed]
  • Pearce RH, Mathieson JM, Mort JS, Roughley PJ. Effect of age on the abundance and fragmentation of link protein of the human intervertebral disc. J Orthop Res. 1989;7(6):861–867. [PubMed]
  • Pearce RH, Grimmer BJ, Adams ME. Degeneration and the chemical composition of the human lumbar intervertebral disc. J Orthop Res. 1987;5(2):198–205. [PubMed]
  • Pearce RH, Thompson JP, Bebault GM, Flak B. Magnetic resonance imaging reflects the chemical changes of aging degeneration in the human intervertebral disk. J Rheumatol Suppl. 1991 Feb;27:42–43. [PubMed]
  • Cole TC, Burkhardt D, Frost L, Ghosh P. The proteoglycans of the canine intervertebral disc. Biochim Biophys Acta. 1985 Apr 17;839(2):127–138. [PubMed]
  • Cole TC, Ghosh P, Taylor TK. Variations of the proteoglycans of the canine intervertebral disc with ageing. Biochim Biophys Acta. 1986 Feb 19;880(2-3):209–219. [PubMed]
  • Lohmander S, Antonopoulos CA, Friberg U. Chemical and metabolic heterogeneity of chondroitin sulfate and keratin sulfate in guinea pig cartilage and nucleus pulposus. Biochim Biophys Acta. 1973 Apr 28;304(2):430–448. [PubMed]
  • Venn G, Mason RM. Biosynthesis and metabolism in vivo of intervertebral-disc proteoglycans in the mouse. Biochem J. 1983 Nov 1;215(2):217–225. [PMC free article] [PubMed]
  • Venn G, Mason RM. Changes in mouse intervertebral-disc proteoglycan synthesis with age. Hereditary kyphoscoliosis is associated with elevated synthesis. Biochem J. 1986 Mar 1;234(2):475–479. [PMC free article] [PubMed]
  • Moore RJ, Osti OL, Vernon-Roberts B, Fraser RD. Changes in endplate vascularity after an outer anulus tear in the sheep. Spine (Phila Pa 1976) 1992 Aug;17(8):874–878. [PubMed]
  • Rudert M, Tillmann B. Lymph and blood supply of the human intervertebral disc. Cadaver study of correlations to discitis. Acta Orthop Scand. 1993 Feb;64(1):37–40. [PubMed]
  • Ohshima H, Urban JP. The effect of lactate and pH on proteoglycan and protein synthesis rates in the intervertebral disc. Spine (Phila Pa 1976) 1992 Sep;17(9):1079–1082. [PubMed]
  • Eyre DR, Muir H. Types I and II collagens in intervertebral disc. Interchanging radial distributions in annulus fibrosus. Biochem J. 1976 Jul 1;157(1):267–270. [PMC free article] [PubMed]
  • Eyre DR, Muir H. Quantitative analysis of types I and II collagens in human intervertebral discs at various ages. Biochim Biophys Acta. 1977 May 27;492(1):29–42. [PubMed]
  • Bushell GR, Ghosh P, Taylor TF, Akeson WH. Proteoglycan chemistry of the intervertebral disks. Clin Orthop Relat Res. 1977 Nov-Dec;(129):115–123. [PubMed]
  • Gower WE, Pedrini V. Age-related variations in proteinpolysaccharides from human nucleus pulposus, annulus fibrosus, and costal cartilage. J Bone Joint Surg Am. 1969 Sep;51(6):1154–1162. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...