Chondrocyte cells respond mechanically to compressive loads

wbldb

Freeman, P. M.¹; Natarajan, R. N.¹; Kimura, J. H.²; Andriacchi, T. P.¹

Chondrocyte cells respond mechanically to compressive loads

J Orthop Res. May 1994;12(3):311-320

Affiliations

¹Department of Orthopedic Surgery, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois

²Bone and Joint Center, Henry Ford Hospital, Deroit, Michigan, U.S.A.
Abstract

Many studies have illustrated the effect of mechanical loading on articular cartilage and the corresponding changes in chondrocyte metabolism, yet the mechanism through which the cells respond to loading still is unclear. The purpose of this study was to evaluate the change in shape of chondrocytes under a statically applied uniaxial compressive load. Isolated chondrocytes from rat chondrosarcoma were embedded in 2% agarose gel. Strains of 5, 10, and 15% were applied, and images of the cell were recorded from initial loading to equilibrium (15 minutes). A finite-element model was used to model the experimental setup and to estimate the mechanical properties of the chondrocyte at equilibrium. The transient behavior of the composite in the experiment was analyzed with use of a standard linear viscoelastic model. We found that all cells decreased in cross-sectional area under each of the applied compressive strains. In the finite-element model, the elasticity of the chondrocyte was similar to that of the surrounding agarose gel (4.0 kPa) and had a Poisson's ratio of 0.4. Viscoelastic analysis showed that the chondrocytes contributed a significant viscoelastic component to the behavior of the composite in comparison with the agarose gel alone. If a decrease in cell volume proportional to the decrease in cross-sectional area is assumed, the decrease observed was greater than would be predicted by a passive cellular response due to an equivalent osmotic pressure. This indicates that the chondrocyte may be altering its intracellular composition by cellular processes in response to mechanical loading.
Links

DOI: 10.1002/jor.1100120303

PubMed: 8207584

WoS: A1994NQ51700002
History

Received: 1991-11-15

Accepted: 1993-07-07

Cited Works (7)

Year	Entry
1986	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(4):393-408.
1988	Gray ML, Pizzanelli AM, Grodzinsky AJ, Lee RC. Mechanical and physicochemical determinants of the chondrocyte biosynthetic response. J Orthop Res. November 1988;6(6):777-792.
1980	Broom ND, Myers DB. A study of the structural response of wet hyaline cartilage to various loading situations. Connect Tissue Res. 1980;7(4):227-237.
1982	Jones IL, Klämfeldt A, Sandström T. The effect of continuous mechanical pressure upon the turnover of articular cartilage proteoglycans in vitro. Clin Orthop Relat Res. May 1982;165:283-289.
1991	Hall AC, Urban JPG, Gehl KA. The effects of hydrostatic pressure on matrix synthesis in articular cartilage. J Orthop Res. January 1991;9(1):1-10.
1989	Sah RL-Y, Kim Y-J, Doong J-YH, Grodzinsky AJ, Plass AHK, Sandy JD. Biosynthetic response of cartilage explants to dynamic compression. J Orthop Res. 1989;7(5):619-636.
1984	Palmoski MJ, Brandt KD. Effects of static and cyclic compressive loading on articular cartilage plugs in vitro. Arthritis Rheum. June 1984;27(6):675-681.

Cited By (66)

Year	Entry
2003	Guilak F, Setton LA. Functional tissue engineering and the role of biomechanical signaling in articular cartilage repair. In: Guilak F, Butler DL, Goldstein SA, Mooney DJ, eds. Functional Tissue Engineering. New York, NY: Inc., Springer-Verlag; 2003:277-290.
2005	Alexopoulos LG, Setton LA, Guilak F. The biomechanical role of the chondrocyte pericellular matrix in articular cartilage. Acta Biomater. May 2005;1(3):317-325.
2001	Elder SH, Goldstein SA, Kimura JH, Soslowsky LJ, Spengler DM. Chondrocyte differentiation is modulated by frequency and duration of cyclic compressive loading. Ann Biomed Eng. June 2001;29(6):476-482.
2004	Hung CT, Mauck RL, Wang CC-B, Lima EG, Ateshian GA. A paradigm for functional tissue engineering of articular cartilage via applied physiologic deformational loading. Ann Biomed Eng. January 2004;32(1):35-49.
2006	Guilak F, Alexopoulos LG, Upton ML, Youn I, Choi JB, Cao L, Setton LA, Haider MA. The pericellular matrix as a transducer of biomechanical and biochemical signals in articular cartilage. Annals NY Acad Sci. April 2006;1068(1):498-512.
2000	Grodzinsky AJ, Levenston ME, Jin M, Frank EH. Cartilage tissue remodeling in response to mechanical forces. Annu Rev Biomed Eng. 2000;2:691-713.
1998	Knight MM, Lee DA, Bader DL. The influence of elaborated pericellular matrix on the deformation of isolated articular chondrocytes cultured in agarose. Biochim Biophys Acta. October 21, 1998;1405:67-77.
1998	Carter DR, Beaupré GS, Giori NJ, Helms JA. Mechanobiology of skeletal regeneration. Clin Orthop Relat Res. October 1998;355(suppl):S41-S55.
1995	Lee DA, Bader DL. The development and characterization of anin vitro system to study strain-induced cell deformation in isolated chondrocytes. In Vitro Cell Dev Biol Anim. December 1995;31(11):828-835.
1995	Guilak F. Compression-induced changes in the shape and volume of the chondrocyte nucleus. J Biomech. December 1995;28(12):1529-1541.
1995	Bachrach NM, Valhmu WB, Stazzone E, Ratcliffe A, Lai WM, Mow VC. Changes in proteoglycan synthesis of chondrocytes in articular cartilage are associated with the time-dependent changes in their mechanical environment. J Biomech. December 1995;28(12):1561-1569.
1999	Jones WR, Ping Ting-Beall H, Lee GM, Kelley SS, Hochmuth RM, Guilak F. Alterations in the young’s modulus and volumetric properties of chondrocytes isolated from normal and osteoarthritic human cartilage. J Biomech. February 1999;32(2):119-127.
2000	Brown TD. Techniques for mechanical stimulation of cells in vitro: a review. J Biomech. January 2000;33(1):3-14.
2000	Lee DA, Knight MM, Bolton JF, Idowu BD, Kayser MV, Bader DL. Chondrocyte deformation within compressed agarose constructs at the cellular and sub-cellular levels. J Biomech. January 2000;33(1):81-95.
2000	Guilak F, Mow VC. The mechanical environment of the chondrocyte: a biphasic finite element model of cell–matrix interactions in articular cartilage. J Biomech. December 2000;33(12):1663-1673.
2003	Gu WY, Yao H, Huang CY, Cheung HS. New insight into deformation-dependent hydraulic permeability of gels and cartilage, and dynamic behavior of agarose gels in confined compression. J Biomech. April 2003;36(4):593-598.
2005	Alexopoulos LG, Williams GM, Upton ML, Setton LA, Guilak F. Osteoarthritic changes in the biphasic mechanical properties of the chondrocyte pericellular matrix in articular cartilage. J Biomech. March 2005;38(3):509-517.
2006	Shieh AC, Athanasiou KA. Biomechanics of single zonal chondrocytes. J Biomech. 2006;39(9):1595-1602.
2000	Lai WM, Mow VC, Sun DD, Ateshian GA. On the electric potentials inside a charged soft hydrated biological tissue: streaming potential versus diffusion potential. J Biomech Eng. August 2000;122(4):336-346.
2003	Baer AE, Laursen TA, Guilak F, Setton LA. The micromechanical environment of intervertebral disc cells determined by a finite deformation, anisotropic, and biphasic finite element model. J Biomech Eng. February 2003;125(1):1-11.
2003	Alexopoulos LG, Haider MA, Vail TP, Guilak F. Alterations in the mechanical properties of the human chondrocyte pericellular matrix with osteoarthritis. J Biomech Eng. June 2003;125(3):323-333.
2003	Koay EJ, Shieh AC, Athanasiou KA. Creep indentation of single cells. J Biomech Eng. June 2003;125(3):334-341.
1995	Buschmann MD, Gluzband YA, Grodzinsky AJ, Hunziker EB. Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J Cell Sci. April 1995;108(4):1497-1508.
1996	Buschmann MD, Hunziker EB, Kim YJ, Grodzinsky AJ. Altered aggrecan synthesis correlates with cell and nucleus structure in statically compressed cartilage. J Cell Sci. February 1996;109(2):499-508.
1997	Lee DA, Bader DL. Compressive strains at physiological frequencies influence the metabolism of chondrocytes seeded in agarose. J Orthop Res. March 1997;15(2):181-188.
1998	Lee DA, Noguchi T, Knight MM, O'Donnell L, Bentley G, Bader DL. Response of chondrocyte subpopulations cultured within unloaded and loaded agarose. J Orthop Res. November 1998;16(6):726-733.
1999	Shin D, Athanasiou K. Cytoindentation for obtaining cell biomechanical properties. J Orthop Res. November 1999;17(6):880-890.
2000	Elder SH, Kimura JH, Soslowsky LJ, Lavagnino M, Goldstein SA. Effect of compressive loading on chondrocyte differentiation in agarose cultures of chick limb-bud cells. J Orthop Res. January 2000;18(1):78-86.
2000	Trickey WR, Lee GM, Guilak F. Viscoelastic properties of chondrocytes from normal and osteoarthritic human cartilage. J Orthop Res. November 2000;18(6):891-898.
2008	Chaudhari AMW, Briant PL, Bevill SL, Koo S, Andriacchi TP. Knee kinematics, cartilage morphology, and osteoarthritis after ACL injury. Med Sci Sports Exer. February 2008;40(2):215-222.
1999	Guilak F, Jones WR, Ting-Beall HP, Lee GM. The deformation behavior and mechanical properties of chondrocytes in articular cartilage. Osteoarthritis Cartilage. January 1999;7(1):59-70.
2006	Darling EM, Zauscher S, Guilak F. Viscoelastic properties of zonal articular chondrocytes measured by atomic force microscopy. Osteoarthritis Cartilage. June 2006;14(6):571-579.
1995	Bachrach NM. Growth Plate Chondrocyte Deformation in Situ and a Biphasic Inclusion Model for Cells Within Hydrated Soft Tissues [PhD thesis]. Columbia University; 1995.
2002	Sun D. Theoretical and Experimental Investigations of the Mechano-Electrochemical Properties of Articular Cartilage, a Charged -Hydrated -Soft, Biological Tissue [PhD thesis]. Columbia University; 2002.
2003	Mauck RL. Functional Tissue Engineering of Articular Cartilage: The Effect of Physical Forces on the in Vitro Growth of Engineered Constructs [PhD thesis]. Columbia University; 2003.
2007	Likhitpanichkul M. The Cell-Matrix Mechano-Electrochemical Interactions in Articular Cartilage: Experiment and Triphasic Model [PhD thesis]. Columbia University; 2007.
2008	Lima EG. The Tissue-Engineering of Functional Osteochondral Constructs for Cartilage Repair [PhD thesis]. Columbia University; 2008.
2018	Holyoak DT. Role of in Vivo Mechanical Loading in the Pathology, Treatment, and Prevention of Osteoarthritis [PhD thesis]. Ithaca, NY: Cornell University; December 2018.
2000	Trickey WR. Mechanical Properties of Chondrocytes [PhD thesis]. Duke University; 2000.
2001	Baer AE. The Micromechanical Environment of Intervertebral Disc Cells [PhD thesis]. Duke University; 2001.
2004	Alexopoulos LG. The Biomechanical Role of the Chondrocyte Pericellular Matrix in Articular Cartilage [PhD thesis]. Duke University; 2004.
2003	Korhonen R. Experimental Analysis and Finite Element Modeling of Normal and Degraded Articular Cartilage: Mechanical Response of Poroelastic, Anisotropic and Inhomogenous Tissue [PhD thesis]. University of Kuopio; 2003.
2004	Yao H. Physical Signals and Solute Transport in Cartilaginous Tissues [PhD thesis]. University of Miami; August 2004.
1999	Ragan PM. The Effect of Mechanical Compression on Chondrocyte Gene Expression [PhD thesis]. Cambridge, MA: Massachusetts Institute of Technology; May 1999.
2005	Ng LJ. Probing Nanomechanics of Aggrecan and the Aggrecan-Rich Pericellular Matrix of Chondrocytes in Cartilage [PhD thesis]. Cambridge, MA: Massachusetts Institute of Technology; September 2005.
2009	Chen S. Regulation of Lubricin Gene Expression and Synthesis in Cartilage by Mechanical Injury [PhD thesis]. Cambridge, MA: Massachusetts Institute of Technology; September 2009.
2009	Lee B. Time-Dependent Mechanical Behavior of Newly Developing Matrix of Bovine Primary Chondrocytes and Bone Marrow Stromal Cells Using Atomic Force Microscopy [PhD thesis]. Cambridge, MA: Massachusetts Institute of Technology; September 2009.
2013	Li Y. In Vitro Model of Injury/cytokine-Induced Cartilage Catabolism Modulated by Dynamic Compression, Growth Factors, and Glucocorticoids [PhD thesis]. Cambridge, MA: Massachusetts Institute of Technology; June 2013.
2024	Davis SL. Using High Resolution X-Ray Computed Tomography and Digital Volume Correlation to Assess Full-Field 3d Strain Distribution Patterns in Osteoarthritic Cartilage [PhD thesis]. Portsmouth, England: University of Portsmouth; 2024.
2012	Kaupp JA. Simulated Joint Loading Enhances the Expression of of Superficial Zone Markers in Tissue Engineered Cartilage Constructs [PhD thesis]. Queen's University; February 2012.
2006	Leipzig ND. Growth Factor Effects on Single Chondrocyte Biomechanics and Gene Expression [PhD thesis]. Houston, TX: Rice University; April 2006.
2006	Shieh AC. Mechanobiology of Single Chondrocytes [PhD thesis]. Houston, TX: Rice University; April 2006.
2007	Koay EJ. Chondrocyte Biomechanics and Chondrogenesis [PhD thesis]. Houston, TX: Rice University; December 2007.
2009	Ofek G. Biomechanics of the Single Chondrocyte and Its Developing Extracellular Matrix [PhD thesis]. Houston, TX: Rice University; May 2009.
2011	Willard VP. Characterization of the Temporomandibular Joint Disc and Fibrocartilage Engineering Using Human Embryonic Stem Cells [PhD thesis]. Houston, TX: Rice University; May 2011.
2005	McGarry JG. Computational and Experimental Investigation of Bone Cell Response to Mechanical Stimuli [PhD thesis]. Trinity College Dublin; September 2005.
2017	Irvine AD. Modulating Mechanical Cues and Oxygen Availability to Regulate Chondrogenesis Within MSC Laden Hydrogels [PhD thesis]. Trinity College Dublin; June 2017.
1996	Hasler EM. In-Vivo Knee Loading Before and After ACL Transection in an Animal Model [PhD thesis]. Calgary, AB: University of Calgary; September 1996.
2009	Han SK. In Situ Chondrocyte Mechanics and Numerical Modeling [PhD thesis]. Calgary, AB: University of Calgary; April 2009.
2013	Madden RMJ. In Situ Chondrocyte Mechanics and Mechanobiology [Master's thesis]. Calgary, AB: University of Calgary; August 2013.
2007	Vigfusdottir AT. Effects of Cytoskeletal Protein Disruption on the Deformation of MSCs During Chondrogenesis [Master's thesis]. University of Maryland; 2007.
2014	Twomey JD. Pericellular Matrix Mechanotransduction Events in Differentiating Human Mesenchymal Stem Cells: Modulating the Pericellular Matrix Through Silencing Type VI Collagen and Decorin [PhD thesis]. University of Maryland; 2014.
1998	Elder SH. Effects of Compressive Loading on Chondrocyte Differentiation in a Novel Chick Limb Bud Cell-Agarose Model of Chondrogenesis [PhD thesis]. University of Michigan; 1998.
2014	O’Conor CJ. TRPV4-Mediated Mechanotransduction in Articular Cartilage Function and Disease [PhD thesis]. University of North Carolina at Chapel Hill; 2014.
2020	Black A. Integrin Alpha 1 Beta 1 Has Limited Influence on Epidermal Growth Factor Receptor Signaling But Sex-Dependent Effects on Estrogen Receptor Beta in Murine Knee Chondrocytes [Master's thesis]. University of Guelph; September 2020.
1996	Shin D. Cytoindentation Theory and Experiment for Obtaining Cell Biomechanical Properties [PhD thesis]. University of Texas at Austin; August 1996.