Effects of Enzymatic Degradation and Supplementation of Chrondroitin Sulfate on the Frictional Properties of Articular Cartilage

The main objective of this thesis was to investigate the role of extracellular matrix components on the mechanism of load support and frictional response of articular cartilage, more specifically through the use of enzymatic degradation and supplementation of chondroitin sulfate. Several experiments were performed in order to investigate: (1) how the mechanism of fluid load support and the time-dependent friction coefficient are affected by enzymatic degradation of the extracellular matrix; and (2) if chondroitin sulfate can reduce the friction coefficient of articular cartilage.

The interstitial fluid plays a fundamental role in the load support mechanism in cartilage, supporting the majority of the applied load and therefore protecting the solid matrix from excessive deformation Collagenase and chondroitinase ABC were used to selectively degrade the collagen matrix and the proteoglycans and investigate the effect on the fluid load support. Results confirmed that the peak fluid load support in unconfined compression decreases significantly after enzymatic degradation. The transient response of the friction coefficient is negatively correlated with the interstitial fluid load support. Proteoglycan removal after chondroitinase ABC digestion caused a significant increase in the time-dependent friction coefficient as the result of a decrease in the fluid load support. Chondroitin sulfate is the major component of the proteoglycans found in articular cartilage. Experimental results showed that supplementation of chondroitin sulfate can significantly reduce the friction coefficient of articular cartilage, suggesting that it could be injected directly into the joint to improve the tribological function.

The results from this dissertation have provided a greater understanding into the frictional properties of articular cartilage and have shown that maintaining the integrity extracellular matrix is fundamental for the proper functioning of the joint. Future studies will investigate whether chondroitin sulfate is a suitable therapy for the treatment of osteoarthritis.

Year	Entry
1991	Ateshian G, Soslowsky L, Mow V. Quantitation of articular surface topography and cartilage thickness in knee joints using stereophotogrammetry. J Biomech. January 1991;24(8):761-776.
1967	Stegemann H, Stalder K. Determination of hydroxyproline. Clin Chim Acta. November 1, 1967;18(2):267.
2001	Huang C-Y, Mow VC, Ateshian GA. The role of flow-independent viscoelasticity in the biphasic tensile and compressive responses of articular cartilage. J Biomech Eng. October 2001;123(5):410-417.
2003	Huang C-Y, Soltz MA, Kopacz M, Mow VC, Ateshian GA. Experimental verification of the roles of intrinsic matrix viscoelasticity and tension-compression nonlinearity in the biphasic response of cartilage. J Biomech Eng. February 2003;125(1):84-93.
1994	Ateshian GA, Lai WM, Zhu WB, Mow VC. An asymptotic solution for the contact of two biphasic cartilage layers. J Biomech. November 1994;27(11):1347-1360.
1995	Ateshian GA, Wang H. A theoretical solution for the frictionless rolling contact of cylindrical biphasic articular cartilage layers. J Biomech. November 1995;28(11):1341-1355.
2004	Chahine NO, Wang CC-B, Hung CT, Ateshian GA. Anisotropic strain-dependent material properties of bovine articular cartilage in the transitional range from tension to compression. J Biomech. August 2004;37(8):1251-1261.
1998	Ateshian GA, Wang H, Lai WM. The role of interstitial fluid pressurization and surface porosities on the boundary friction of articular cartilage. J Tribol. April 1998;120(2):241-248.
1983	Brown TD, Shaw DT. In vitro contact stress distributions in the natural human hip. J Biomech. 1983;16(6):373-384.
1982	Armstrong CG, Mow VC. Variations in the intrinsic mechanical properties of human articular cartilage with age, degeneration, and water content. J Bone Joint Surg. 1982;64A(1):88-94.
1983	Ahmed AM, Burke DL. In-vitro of measurement of static pressure distribution in synovial joints, I: tibial surface of the knee. J Biomech Eng. August 1983;105(3):216-225.
1999	Setton LA, Elliott D., Mow VC. Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration. Osteoarthritis Cartilage. January 1999;7(1):2-14.
2001	Chen SS, Falcovitz YH, Schneiderman R, Maroudas A, Sah RL. Depth-dependent compressive properties of normal aged human femoral head articular cartilage: relationship to fixed charge density. Osteoarthritis Cartilage. August 2001;9(6):561-569.
1994	Guilak F, Ratcliffe A, Lane N, Rosenwasser MP, Mow VC. Mechanical and biochemical changes in the superficial zone of articular cartilage in canine experimental osteoarthritis. J Orthop Res. July 1994;12(4):474-484.
1971	Hayes WC, Mockros LF. Viscoelastic properties of human articular cartilage. J Appl Physiol. October 1971;31(4):562-568.
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1977	Parsons JR, Black J. The viscoelastic shear behavior of normal rabbit articular cartilage. J Biomech. 1977;10(1):21-29.
1997	Ateshian GA, Warden W, Kim JJ, Grelsamer RP, Mow VC. Finite deformation biphasic material properties of bovine articular cartilage from confined compression experiments. J Biomech. November–December 1997;30:1157.
1986	Holmes MH. Finite deformation of soft tissue: analysis of a mixture model in uni-axial compression. J Biomech Eng. November 1986;108(4):372-381.
1986	Mak AF. The apparent viscoelastic behavior of articular cartilage: the contributions from the intrinsic matrix viscoelasticity and interstitial fluid flows. J Biomech Eng. May 1986;108(2):123-130.
1991	Lai WM, Hou JS, Mow VC. A triphasic theory for the swelling and deformation behaviors of articular cartilage. J Biomech Eng. August 1991;113(3):245-258.
1995	Setton LA, Mow VC, Howell DS. Mechanical behavior of articular cartilage in shear is altered by transection of the anterior cruciate ligament. J Orthop Res. July 1995;13(4):473-482.
1979	Kempson GE. Mechanical properties of articular cartilage. In: Freeman MAR, ed. Adult Articular Cartilage. 2nd ed. Kent, England: Pitman Medical; 1979:333-414.
1976	Malcom LL. An Experimental Investigation of the Frictional and Deformational Responses of Articular Cartilage Interfaces to Static and Dynamic Loading [PhD thesis]. San Diego (UCSD), University of California; 1976.
1971	Kempson GE, Spivey CJ, Swanson SAV, Freeman MAR. Patterns of cartilage stiffness on normal and degenerate human femoral heads. J Biomech. December 1971;4(6):597-609.
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1971	Kempson GE, Freeman MAR, Swanson SAV. The determination of a creep modulus for articular cartilage from indentation tests on the human femoral head. J Biomech. July 1971;4(4):239-250.
1984	Armstrong CG, Lai WM, Mow VC. An analysis of the unconfined compression of articular cartilage. J Biomech Eng. May 1984;106(2):165-173.
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1990	Kwan MK, Lai WM, Mow VC. A finite deformation theory for cartilage and other soft hydrated connective tissues, I: equilibrium results. J Biomech. 1990;23(2):145-155.
1982	Farndale RW, Sayers CA, Barrett AJ. A direct spectrophotometric microassay for sulfated glycosaminoglycans in cartilage cultures. Connect Tissue Res. 1982;9(4):247-248.
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1992	Cohen B. Anisotropic Hydrated Soft Tissues in Finite Deformation and the Biomechanics of the Growth Plate [PhD thesis]. Columbia University; 1992.
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1968	Kempson GE, Freeman MAR, Swanson SAV. Tensile properties of articular cartilage. Nature. December 14, 1968;220(5172):1127-1128.
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1980	Mow VC, Kuei SC, Lai WM, Armstrong CG. Biphasic creep and stress relaxation of articular cartilage in compression: theory and experiments. J Biomech Eng. February 1980;102(1):73-84.
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2003	Park S, Krishnan R, Nicoll SB, Ateshian GA. Cartilage interstitial fluid load support in unconfined compression. J Biomech. December 2003;36(12):1785-1796.
1990	Holmes MH, Mow VC. The nonlinear characteristics of soft gels and hydrated connective tissues in ultrafiltration. J Biomech. 1990;23(11):1145-1156.
1999	Soulhat J, Buschmann MD, Shirazi-Adl A. A fibril-network-reinforced biphasic model of cartilage in unconfined compression. J Biomech Eng. June 1999;121(3):340-347.
2000	Soltz MA, Ateshian GA. A conewise linear elasticity mixture model for the analysis of tension-compression nonlinearity in articular cartilage. J Biomech Eng. December 2000;122(6):576-586.
1993	Zhu W, Mow VC, Koob TJ, Eyre DR. Viscoelastic shear properties of articular cartilage and the effects of glycosidase treatments. J Orthop Res. November 1993;11(6):771-781.
2004	Krishnan R, Kopacz M, Ateshian GA. Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication. J Orthop Res. May 2004;22(3):565-570.
1962	McCutchen CW. The frictional properties of animal joints. Wear. January–February 1962;5(1):1-17.
1986	Akizuki S, Mow VC, Müller F, Pita JC, Howell DS, Manicourt DH. 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(4):379-392.
1979	Maroudas A. Physicochemical properties of articular cartilage. In: Freeman MAR, ed. Adult Articular Cartilage. 2nd ed. Kent, England: Pitman Medical; 1979:215-290.
1994	Macirowski T, Tepic S, Mann RW. Cartilage stresses in the human hip joint. J Biomech Eng. February 1994;116(1):10-18.
1998	Quapp KM, Weiss JA. Material characterization of human medial collateral ligament. J Biomech Eng. December 1998;120(6):757-763.
1981	Swann DA, Slayter HS, Silver FH. The molecular structure of lubricating glycoprotein-i, the boundary lubricant for articular cartilage. J Biol Chem. June 10, 1981;256(11):5921-5925.
1997	Schinagl RM, Gurskis D, Chen AC, Sah RL. Depth-dependent confined compression modulus of full-thickness bovine articular cartilage. J Orthop Res. July 1997;15(4):499-506.
1990	Schmidt MB, Mow VC, Chun LE, Eyre DR. Effects of proteoglycan extraction on the tensile behavior of articular cartilage. J Orthop Res. May 1990;8(3):353-363.

Year

Entry

1991

Ateshian G, Soslowsky L, Mow V. Quantitation of articular surface topography and cartilage thickness in knee joints using stereophotogrammetry. J Biomech. January 1991;24(8):761-776.

1967

Stegemann H, Stalder K. Determination of hydroxyproline. Clin Chim Acta. November 1, 1967;18(2):267.

2001

Huang C-Y, Mow VC, Ateshian GA. The role of flow-independent viscoelasticity in the biphasic tensile and compressive responses of articular cartilage. J Biomech Eng. October 2001;123(5):410-417.

2003

Huang C-Y, Soltz MA, Kopacz M, Mow VC, Ateshian GA. Experimental verification of the roles of intrinsic matrix viscoelasticity and tension-compression nonlinearity in the biphasic response of cartilage. J Biomech Eng. February 2003;125(1):84-93.

1994

Ateshian GA, Lai WM, Zhu WB, Mow VC. An asymptotic solution for the contact of two biphasic cartilage layers. J Biomech. November 1994;27(11):1347-1360.