Viscometric Properties of Proteoglycan Solutions at Physiological Concentrations

  • W. B. Zhu
  • V. C. Mow


Proteoglycans are important components of the extracellular matrix of articular cartilage and other soft tissues. The structural organization of these macromolecules is believed to be significant for maintaining the cohesion of the extracellular matrix, and thus influences the material properties of the tissue as a whole (Pottenger et al. 1982; Muir 1983). Recent studies have shown that the structure of proteoglycans varies with cartilage age and pathology (Hjertquist and Wasteson 1972; Bayliss and Ali 1979; Muir 1977, 1980, 1983; Roughley and White 1980; Pal et al. 1981; Buckwalter et al. 1983; Buckwalter and Rosenberg 1985). In general, as cartilage ages and degenerates, proteoglycan size decreases (i.e. lower molecular weight) and the percentage of non- aggregated forms increases. The decrease in proteoglycan size and percentage aggregation has been shown to be important factors in increased mobility of the proteoglycan within the collagen meshwork (Pottenger et al. 1982; Muir 1983). Link proteins serve to stabilize proteoglycan aggregates by joining the proteoglycan monomers to a linear hyaluronate chain (Hardingham 1979,1981). Changes in proteoglycan aggregation may involve abnormalities in the hyaluronate binding region of the monomer or the link protein (Muir 1977, 1983; Hardingham 1979,1981; Plaas and Sandy 1984; Poole 1986; Ratcliffe et al. 1986). These changes tend to alter the collagen-proteoglycan and proteoglycan-proteoglycan interactions (Obrink 1973; Myers et al. 1984b; Mow et al. 1989), causing possible migration of proteoglycan fragments through, and loss from, the extracellular matrix (Brandt 1974; Muir 1977; Bayliss and Ali 1979; Ratcliffe et al. 1986).


Shear Rate Articular Cartilage Link Protein Junction Site Dynamic Shear Modulus 
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  1. Adams M: Cartilage and osteoarthritis: changes of collagen and proteoglycans. Czech Med 1979; 2:64–68.Google Scholar
  2. Akizuki S, Mow VC, Muller F, Pita JC, Howell DS, Manicourt DH: The tensile properties of human knee joint cartilage: I. Influence of ionic conditions, weight bearing, and fibrillation on the tensile modulus. J Orthop Res 1986; 4(3):379–392.CrossRefGoogle Scholar
  3. Armstrong CG, Bahrani AS, Gardner DL: In vitro measurement of articular cartilage deformation in the intact human hip joint under load. J Bone Joint Surg 1979; 61- A:744–755.Google Scholar
  4. Armstrong CG, Mow VC: Variations in the intrinsic mechanical properties of human cartilage with age, degeneration and water content. J Bone Joint Surg 1982a; 64- A:88–94.Google Scholar
  5. Armstrong CG, Mow VC: Biomechanics of normal and osteoarthrotic articular cartilage, in Wilson PD, Straub LR (eds): Clinical Trends in Orthopaedics. New York, Thieme- Stratton, Inc, 1982b, pp 189–197.Google Scholar
  6. Balazs EA, Gibbs DA: In Chemistry and Molecular Biology of the Intercellular Matrix, Balazs EA (eds), Academic Press, 1970, pp. 1241–1257.Google Scholar
  7. Bayliss MT, Ali SY: Age-related changes in the composition and structure of human articular cartilage proteoglycans. Biochem J 1979; 176:683–693.Google Scholar
  8. Bird RB, Armstrong RC, Hassager O: Dynamics of Polymeric Liquids: Fluid Mechanics, John Wiley & Sons, Ins, New York 1977a.Google Scholar
  9. Bird RB, Hassager O, Armstrong RC, Curtiss CF: Dynamics of Polymeric Liquids: Kinetic theory, John Wiley & Sons, Ins, New York 1977b.Google Scholar
  10. Bollet AJ, Nance JL: Biochemical findings in normal and osteoarthritic articular cartilage, II. chondroitin sulfate concentration and chain length, water and ash content. J Clinical Investigation 1966; 45(7):1170–1177.CrossRefGoogle Scholar
  11. Brandt KD: Enhanced extractability of articular cartilage proteoglycans in osteoarthrosis. Biochem J 1974; 143:475–478.Google Scholar
  12. Buckwalter JA, Kuettner KE, Thonar EJ-M: Age-related changes in articular cartilage proteoglycans: electron microscopic studies. J Orthop Res 1985; 3:251–257.CrossRefGoogle Scholar
  13. Buckwalter JA, Rosenberg LC: Structural changes during development in bovine fetal epiphyseal cartilage: Electron microscopic studies of proteoglycan monomers and aggregates. Collagen Rel Res 1983; 3: 489–504.Google Scholar
  14. Carney SL, Billingham MEJ, Muir H, Sandy JD: Demonstration of increased proteoglycan turnover in cartilage explants from dogs with experimental arthritis. J Orthop Ser 1984; 2:201–206.Google Scholar
  15. Coleman BD, Markowitz H, Noll W: Viscometric flows of non-Newtonian Fluids, Springer- Verlag, New York, 1966.Google Scholar
  16. De Kee D, Carreau PJ: A Constitutive Equation Derived from Lodge’s Network Theory. J Non-Newtonian F1 Mech 1979; 6:127–143.MATHCrossRefGoogle Scholar
  17. Eisenberg SR, Grodzinsky A J: The kinetics of chemically induced nonequilibrium swelling of articular cartilage and corneal stroma. J Biomech Eng 1987; 109:79–89.CrossRefGoogle Scholar
  18. Eyre DR, Koob TJ, Van Ness KP: Quantitation of hydroxypyridinium crosslinks in collagen by high-performance liquid chromatography. Analytical Biochem 1984; 137:308–388.CrossRefGoogle Scholar
  19. Ferry JD: Viscoelastic Properties of Polymers, Wiley, New York, Second Edition 1970.Google Scholar
  20. Gray ML, Pizzanelli AM, Grodzinsky A J, Lee RC: Mechanical and physicochemical determinants of the chondrocyte biosynthetic response. J Orthop Res 1988; 6:777–792.CrossRefGoogle Scholar
  21. Hardingham TE: The role of link protein in the structure of cartilage proteoglycan aggregates. Biochem J 1979; 177:237–247.Google Scholar
  22. Hardingham TE: Proteoglycans: Their structure, interactions and molecular organization in cartilage. Biochem Soc Trans 1981; 9:489–497.Google Scholar
  23. Hardingham TE, Meardmore-Grey M, Dunham DG: Protein domain structure of the aggregating proteoglycan from cartilage. Trans Orthop Res Soc 1987a; 12:61.Google Scholar
  24. Hardingham TE, Muir H, Kwan MK, Lai WM, Mow VC: Viscoelastic properties of proteoglycan solutions with varying proportions present as aggregates. J Orthop Res 1987b; 5:36–46.CrossRefGoogle Scholar
  25. Hascall VC, Hascall GK: Proteoglycans, in Hay ED (ed) Cell Biology of Extracellular Matrix, Plenum Press, New York, 1981, pp 39–63.Google Scholar
  26. Hascall VC, Sajdesa F: Proteinpolysaccharide complex from bovine nasal cartilage, the function of glycoprotein in the formation of aggregates. J Biol Chem 1969, 244:2384–2396.Google Scholar
  27. Hjertquist SO, Wasteson A: The molecular weight of chondroitin sulfate from human articular cartilage: effect of age and of osteoarthritis. Calcif Tissue Res 1972; 10:31–37.CrossRefGoogle Scholar
  28. Jaffe FF, Mankin HJ, Weiss C, Zarins A: Water binding in the articular cartilage of rabbits. J Bone Joint Surg 1974; 56A:1031–1039.Google Scholar
  29. Kempson GE: Mechanical properties of articular cartilage, in Freeman MAR (ed) Adult Articular Cartilage, Tunbridge Wells, England, Pitman Medical, 1979, pp 333–414.Google Scholar
  30. Lai WM, Hou J, Mow VC: Triphasic theory for articular cartilage swelling, in Torzill PA, Friedman MH (eds) Proc Biomech Symp, San Diego, ASME, 1989, pp 33–36.Google Scholar
  31. Lodge AS: Constitutive equations from molecular network theories for polymer solutions. Rheol Acta 1968; 7:379–392.MATHCrossRefGoogle Scholar
  32. Mak AF, Mow VC, Lai WM, Hardingham TE, Muir H, Eyre DR: Assessment of proteoglycan-proteoglycan interactions from solution biorheological behavior. Trans Orthop Res Soc 1982; 7:169.Google Scholar
  33. Mak AF, Mow VC, Lai WM, Hardingham TE, Muir H: Predictions of the Number and Strength of the Proteoglycan-Proteoglycan Interactions from Viscometric Data. Trans Orthop Res Soc 1983; 8:3.Google Scholar
  34. Mankin HJ, Thrasher AZ: Water content and binding in normal and osteoarthritic human cartilage. J Bone Joint Surg 1975; 57A:76–80.Google Scholar
  35. Maroudas A: Physicochemical properties of articular cartilage, in Freeman MAR (ed) Adult Articular Cartilage, Tunbridge Wells, England, Pitman Medical, 1979, pp 215–290.Google Scholar
  36. Maroudas A: Physical chemistry of articular cartilage and the intervertebral disc, in Sokoloff L (ed) The Joint and Synovial Fluid, II, New York Academic Press, 1980, pp 239–291.Google Scholar
  37. Maroudas A: Proteoglycan osmotic pressure and collagen tension in normal, osteoarthritic human cartilage, in Huskisson EC, Katona G (eds) Int Symp New Trends in Osteoarthritis, 1981, pp. 36–39.Google Scholar
  38. McDevitt CA, Muir H: Biochemical changes in the cartilage of the knee in experimental and natural osteoarthrosis in the dog. J Bone Joint Surg 1976; 58-B:94–101.Google Scholar
  39. Mow VC, Lai WM (1980): Recent developments in synovial joint biomechanics. SIAM Rev 1980; 22(3): 275–317.MathSciNetMATHCrossRefGoogle Scholar
  40. Mow VC, Holmes MH, Lai WM: Fluid transport and mechanical properties of articular cartilage: A review. J Biomech 1984a; 17:377–394.CrossRefGoogle Scholar
  41. Mow VC, Mak AF, Lai WM, Rosenberg LC, Tang LH: Viscoelastic properties of proteoglycan subunits and aggregates in varying solution concentrations. J Biomech 1984b; 17:325–338.CrossRefGoogle Scholar
  42. Mow VC, Zhu WB, Lai WM, Hardingham TE, Hughes C, Muir H: The influence of link protein stabilization on the viscometric properties of proteoglycan aggregate solutions. Biochim Biophys Acta 1989; 992:201–208.Google Scholar
  43. Muir H: A molecular approach to the understanding of osteoarthrosis. Ann Rheum Dis 1977; 36:199–208.CrossRefGoogle Scholar
  44. Muir H: The chemistry of the ground substance of joint cartilage, in Sokoloff L (ed) The Joints and Synovial Fluid, Vol II. New York, Academic Press, 1980, pp 27–94.Google Scholar
  45. Muir H: Proteoglycans as organizers of the extracellular matrix. Biochem Soc Trans 1983; 11:613–622.Google Scholar
  46. Myers ER, Zhu WB, Mow VC: Viscoelastic properties of articular cartilage and meniscus, in Nimni ME (ed) Collagen, Biochemistry, Biology and Biotechnology, Vol II. CRC Press, Boca Raton, FL, 1987, pp 267–288.Google Scholar
  47. Myers, E.R. Lai, W.M. and Mow, V.C.: A continuum theory and an experiment for the ion-induced swelling behavior of articular cartilage. J. Biomech. Eng. 106:151–158, 1984a.CrossRefGoogle Scholar
  48. Myers, ER, Armstrong, CG, Mow, VC. Swelling pressure and collagen tension. In Connective Tissue Matrix, ed. DWL Hukins, MacMillan Press, Ltd, 1984;161–168, 1984b.Google Scholar
  49. Nimni ME, Harkness RD: Molecular structure and function of collagen, in Nimni ME (ed) Collagen: Biochemistry, Vol I. CRC Press, Boca Raton, Florida, 1988, pp 1–78.Google Scholar
  50. Obrink B: A study of the interactions between sununitic tropocollagen and glycosaminoglycan. Euro J Biochem 1973; 33:387–400.CrossRefGoogle Scholar
  51. Oldroyd JG: On the formulation of rheological equations of state. Proc R Soc 1950; A- 250:523–541.MathSciNetGoogle Scholar
  52. Pal S, Tang LH, Choi H, Habermann E, Rosenberg LC, Roughley P, Poole AR: Structural changes during development in bovine fetal epiphyseal cartilage. Coll Res 1981; 1:151–176.Google Scholar
  53. Paulsson M, Morgelin M, Wiedemann H, Beardmore-Gray M, Dunham D, Hardingham TE, Heinegard D, Timpl R, Engel JHH: Extracted and globular protein domains in cartilage proteoglycans. Biochem J 1987; 245:763–772.Google Scholar
  54. Plaas AHK, Sandy JD: Age-related decrease in the link-stability of proteoglycan aggregates formed by articular chondrocytes. Biochem J 1984; 220:337–340.Google Scholar
  55. Poole AR: Proteoglycans in health and disease: structure and functions. Biochem J 1986; 236:1–14.Google Scholar
  56. Pottenger LA, Lyon NB, Hecht JD, Neustadt PM, Robinson RA: Influence of cartilage particle size and proteoglycan aggregation on immobilization of proteoglycans. J Biol Chem 1982; 257:11479–11485.Google Scholar
  57. Ratcliffe A, Tyler J, Hardingham TE: Articular Cartilage Cultured with Interleukin 1: Increase release of Link Protein, Hyaluronate-Binding Region and Other Proteoglycan Fragments. Biochem J 1986; 238:571–580.Google Scholar
  58. Ratcliffe A, Billingham MEJ, Muir H, Hardingham TE: Experimental canine osteoarthritis and cartilage explant culture: increased release of specific proteoglycan components. Trans Orthop Res Soc 1989; 14.Google Scholar
  59. Ricard-Blum S, Tiollier J, Garrone R, Herbage D: Further Biochemical and physicochemical characterization of minor disulfide-bonded (Type DC) collagen, extracted from foetal calf cartilage. J Cellular Biochem 1985; 27:347–358.CrossRefGoogle Scholar
  60. Rosenberg LC, Pal S, Beale R: Proteoglycans from bovine proximal humeral articular cartilage. J Biol Chem 1973; 218:3681–3690.Google Scholar
  61. Rosenberg LC, Wolfenstein-Todel C, Margolis R, Pal S, Strider W: Proteoglycans from bovine proximal humeral articular cartilage: structural basis for the polydispersity of proteoglycan subunit. J Biolo Chem 1976; 251(20):6439–6444.Google Scholar
  62. Rosenberg LC, Choi HU, Tang LH, Johnson TL, Pal S: Isolation of dermatan sulfate proteoglycans from mature bovine articular cartilages. J Biol Chem 1985; 260:6304–6313.Google Scholar
  63. Rosenberg LC, Mow VC, Buckwalter JA, Poole AR: Structure and function of proteoglycans in developing cartilage, in Akeson WH, Bornstein P, Glimcher MJ (eds) American Academy of Orthop Surg Symp on Heritable Disorders of Connective Tissue. CV Mosby Co, St Louis, 1982, pp 285–306.Google Scholar
  64. Roth V, Mow VC: The intrinsic tensile behavior of the matrix of bovine articular cartilage and its variation with age. J Bone Joint Surg 1980; 62-A: 1102–1117.Google Scholar
  65. Roughley PJ, White R J: Age-related changes in the structure of the proteoglycan subunits from human articular cartilage. J Biolo Chem 1980; 255(1):217–224.Google Scholar
  66. Sampaio UD, Bayliss MT, Hardingham TE, Muir H: Dermatan sulphate proteoglycan from human articular cartilage. Biochem J 1988; 254:757–764.Google Scholar
  67. Sandy JD, Adams ME, Billingham MEJ, Plaas A, Muir H: In vivo and in vitro stimulation of chondrocyte biosynthetic activity in early experimental osteoarthritis. Arthritis Rheum 1984; 27:388–397.CrossRefGoogle Scholar
  68. Santer V, White RJ, Roughley PJ: O-linked oligosaccharides of human articular cartilage proteoglycan. Biochim Biophys Acta 1982; 716:277–282.Google Scholar
  69. Schmidt MB, Schoonbeck JM, Mow VC, Eyre DR, Chun LE: Effects of enzymatic extraction of proteoglycans on the tensile properties of articular cartilage. Trans Orthop Res Soc 1986; 11:450.Google Scholar
  70. Schmidt MB, Schoonbeck JM, Mow VC, Eyre DR, Chun LE: The relationship between collagen cross–linking and the tensile properties of articular cartilage. Trans Orthop Res Soc 1987; 12:134.Google Scholar
  71. Schneiderman R, Keret D, Maroudas A: Effects of mechanical and osmotic pressure on the rate of glycosaminoglycan synthesis in the human adult femoral head cartilage: an in vitro study. J Orthop Res 1986; 4:393–408.CrossRefGoogle Scholar
  72. Schurz J, Ribitsch V: Rheology of synovial fluid. Biorheology 1987; 24:385–399.Google Scholar
  73. Simon WH, Mak A, Spirt A: The effect of shear fatigue on bovine articular cartilage. J Orthop Res 1989; 8:86–93.CrossRefGoogle Scholar
  74. Sweet MBE, Thonar E J-M, Immelman AR, Solomon L: Biochemical changes in progressive osteoarthrosis. Ann Rheum Dis 1977; 36:387–398.CrossRefGoogle Scholar
  75. Sweet MBE, Coelho A, Schnitzler CM, Schnitzer TJ, Lenz ME, Jakim I, Kuettner KE, Thonar E J-M A: Serum keratan sulfate levels in osteoarthritis patients. Arthritis and Rheum 1988; 31(5):648–652.CrossRefGoogle Scholar
  76. van der Rest M, Mayne R: Type DC collagen proteoglycan from cartilage is covalently cross-linked to type II collagen. J Biol Chem 1988; 263:1615–1618.Google Scholar
  77. Vasan N: Proteoglycans in normal and severely osteoarthritic human cartilage. Biochem J 1980; 187:781–787.Google Scholar
  78. Walters K: Rheometry. Halsted Press, New York, 1975.Google Scholar
  79. Woo SL-Y, Akeson WH, Jemmott GF: Measurements of nonhomogeneous directional mechanical properties of articular cartilage in tension. J Biomech 1976; 9:785–791.CrossRefGoogle Scholar
  80. Yamauchi M, Mechanic G: Cross-linking of collagen, in Nimni ME (ed) Collagen: Biochemistry, Vol I. CRC Press, Boca Raton, Florida, 1988, pp 157–172.Google Scholar
  81. Zhu WB, Lai WM, Mow VC, Tang LH, Rosenberg LC, Hughes C, Hardingham TE, Muir H: Influence of composition, size and structure of cartilage proteoglycans on the strength of molecular network formed in solution. Trans Orthop Res Sei 1988a; 13:67.Google Scholar
  82. Zhu WB, Lai WM, Mow VC: A second order rheological model to predict the time- dependent behavior of proteoglycan solutions. 1988 Advances in Bioengineering, Trans ASME 1988b; 8:187–190.Google Scholar

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© Springer-Verlag New York Inc. 1990

Authors and Affiliations

  • W. B. Zhu
  • V. C. Mow

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