Abstract
Articular cartilage injury can cause post-traumatic osteoarthritis, but early processes leading to the disease are not well understood. The objective of this study was to characterize two levels of impact loading at 24 h, 1 week, and 4 weeks in terms of cell death, gene expression, extracellular matrix biochemistry, and tissue biomechanical properties. The data show cell death increased and tissue stiffness decreased by 24 h following High impact (2.8 J). These degradative changes persisted at 1 and 4 weeks, and were further accompanied by measurable changes in ECM biochemistry. Moreover, following High impact at 24 h there were specific changes in gene expression that distinguished injured tissue from adjacent tissue that was not loaded. In contrast, Low impact (1.1 J) showed little change from control specimens at 24 h or 1 week. However, at 4 weeks, a significant increase in cell death and significant decrease in tissue stiffness were present. The constellation of findings indicates Low impacted tissue exhibited a delayed biological response. The study characterizes a model system for examining the biology of articular cartilage post-impact, as well as identifies possible time points and success criteria to be used in future studies employing intervention agents.
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Allen K. D., K. A. Athanasiou. Growth factor effects on passaged tmj disk cells in monolayer and pellet cultures. Orthod. Craniofac. Res. 9:143–152, 2006
Almarza A. J., K. A. Athanasiou. Seeding techniques and scaffolding choice for tissue engineering of the temporomandibular joint disk. Tissue Eng. 10:1787–1795, 2004
Aspden R. M., J. E. Jeffrey, L. V. Burgin. Impact loading of articular cartilage. Osteoarthr. Cartilage 10:588–589; author reply 590, 2002
Athanasiou K. A., A. Agarwal, A. Muffoletto, F. J. Dzida, G. Constantinides, M. Clem. Biomechanical properties of hip cartilage in experimental animal models. Clin. Orthop. 316:254–266, 1995
Blanco F. J., R. Guitian, E. Vazquez-Martul, F. J. de Toro, F. Galdo. Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology. Arthritis Rheum. 41:284–289, 1998
Browning J. A., R. E. Walker, A. C. Hall, R. J. Wilkins. Modulation of na+ × h+ exchange by hydrostatic pressure in isolated bovine articular chondrocytes. Acta Physiol. Scand. 166:39–45, 1999
Burton-Wurster N., R. G. Mateescu, R. J. Todhunter, K. M. Clements, Q. Sun, V. Scarpino, G. Lust. Genes in canine articular cartilage that respond to mechanical injury: gene expression studies with affymetrix canine genechip. J. Hered. 96:821–828, 2005
Chan P. S., A. E. Schlueter, P. M. Coussens, G. J. Rosa, R. C. Haut, M. W. Orth. Gene expression profile of mechanically impacted bovine articular cartilage explants. J. Orthop. Res. 23:1146–1151, 2005
Darling E. M., K. A. Athanasiou. Rapid phenotypic changes in articular chondrocyte subpopulations. J. Orthop. Res. 23:425–432, 2005
DiMicco M. A., P. Patwari, P. N. Siparsky, S. Kumar, M. A. Pratta, M. W. Lark, Y. J. Kim, A. J. Grodzinsky. Mechanisms and kinetics of glycosaminoglycan release following in vitro cartilage injury. Arthritis Rheum. 50:840–848, 2004
Duda G. N., M. Eilers, L. Loh, J. E. Hoffman, M. Kaab, K. Schaser. Chondrocyte death precedes structural damage in blunt impact trauma. Clin. Orthop. 393: 302–309, 2001
Ewers B. J., D. Dvoracek-Driksna, M. W. Orth, R. C. Haut. The extent of matrix damage and chondrocyte death in mechanically traumatized articular cartilage explants depends on rate of loading. J. Orthop. Res. 19:779–784, 2001
Ewers B. J., W. N. Newberry, R. C. Haut. Chronic softening of cartilage without thickening of underlying bone in a joint trauma model. J. Biomech. 33:1689–1694, 2000
Ewers B. J., B. T. Weaver, E. T. Sevensma, R. C. Haut. Chronic changes in rabbit retro-patellar cartilage and subchondral bone after blunt impact loading of the patellofemoral joint. J. Orthop. Res. 20:545–550, 2002
Fehrenbacher A., E. Steck, M. Rickert, W. Roth, W. Richter. Rapid regulation of collagen but not metalloproteinase 1, 3, 13, 14 and tissue inhibitor of metalloproteinase 1, 2, 3 expression in response to mechanical loading of cartilage explants in vitro. Arch. Biochem. Biophys. 410:39–47, 2003
Gelse K., S. Soder, W. Eger, T. Diemtar, T. Aigner. Osteophyte development–molecular characterization of differentiation stages. Osteoarthr. Cartilage 11:141–148, 2003
Gelse K., K. von der Mark, T. Aigner, J. Park, H. Schneider. Articular cartilage repair by gene therapy using growth factor-producing mesenchymal cells. Arthritis Rheum. 48:430–441, 2003
Hall A. C. Differential effects of hydrostatic pressure on cation transport pathways of isolated articular chondrocytes. J. Cell. Physiol. 178:197–204, 1999
Hasler E. M., W. Herzog, J. Z. Wu, W. Muller, U. Wyss. Articular cartilage biomechanics: theoretical models, material properties, and biosynthetic response. Crit. Rev. Biomed. Eng. 27:415–488, 1999
Haut R. C. Contact pressures in the patellofemoral joint during impact loading on the human flexed knee. J. Orthop. Res. 7:272–280, 1989
Hayman D. M., T. J. Blumberg, C. C. Scott, K. A. Athanasiou. The effects of isolation on chondrocyte gene expression. Tissue Eng. 12:2573–2581, 2006
Huser C. A., M. E. Davies. Validation of an in vitro single-impact load model of the initiation of osteoarthritis-like changes in articular cartilage. J. Orthop. Res. 24:725–732, 2006
Jeffrey J. E., R. M. Aspden. The biophysical effects of a single impact load on human and bovine articular cartilage. Proc. Inst. Mech. Eng. [H] 220:677–686, 2006
Jeffrey J. E., D. W. Gregory, R. M. Aspden. Matrix damage and chondrocyte viability following a single impact load on articular cartilage. Arch. Biochem. Biophys. 322:87–96, 1995
Jeffrey J. E., L. A. Thomson, R. M. Aspden. Matrix loss and synthesis following a single impact load on articular cartilage in vitro. Biochim. Biophys. Acta 1334:223–232, 1997
Kim Y. J., R. L. Sah, J. Y. Doong, A. J. Grodzinsky. Fluorometric assay of DNA in cartilage explants using hoechst 33258. Anal. Biochem. 174:168–176, 1988
Krueger J. A., P. Thisse, B. J. Ewers, D. Dvoracek-Driksna, M. W. Orth, R. C. Haut. The extent and distribution of cell death and matrix damage in impacted chondral explants varies with the presence of underlying bone. J. Biomech. Eng. 125:114–119, 2003
Kurz B., M. Jin, P. Patwari, D. M. Cheng, M. W. Lark, A. J. Grodzinsky. Biosynthetic response and mechanical properties of articular cartilage after injurious compression. J. Orthop. Res. 19:1140–1146, 2001
Lee J. H., J. B. Fitzgerald, M. A. Dimicco, A. J. Grodzinsky. Mechanical injury of cartilage explants causes specific time-dependent changes in chondrocyte gene expression. Arthritis Rheum. 52:2386–2395, 2005
Levin A., N. Burton-Wurster, C. T. Chen, G. Lust. Intercellular signaling as a cause of cell death in cyclically impacted cartilage explants. Osteoarthr. Cartilage 9:702–711, 2001
Lewis J. L., L. B. Deloria, M. Oyen-Tiesma, R. C. Thompson, M. Ericson, T. R. Oegema. Cell death after cartilage impact occurs around matrix cracks. J. Orthop. Res. 21:881–887, 2003
Lohmander L. S., T. Saxne, D. K. Heinegard. Release of cartilage oligomeric matrix protein (comp) into joint fluid after knee injury and in osteoarthritis. Ann. Rheum. Dis. 53:8–13, 1994
Malemud C. J., R. Shuckett, V. M. Goldberg. Changes in proteoglycans of human osteoarthritic cartilage maintained in explant culture: implications for understanding repair in osteoarthritis. Scand. J. Rheumatol. Suppl. 77:7–12, 1988
Milentijevic D., P. A. Torzilli. Influence of stress rate on water loss, matrix deformation and chondrocyte viability in impacted articular cartilage. J. Biomech. 38:493–502, 2005
Morel V., T. M. Quinn. Cartilage injury by ramp compression near the gel diffusion rate. J. Orthop. Res. 22:145–151, 2004
Mow V. C., M. C. Gibbs, W. M. Lai, W. B. Zhu, K. A. Athanasiou. Biphasic indentation of articular cartilage–ii. A numerical algorithm and an experimental study. J. Biomech. 22:853–861, 1989
Patwari P., M. N. Cook, M. A. DiMicco, S. M. Blake, I. E. James, S. Kumar, A. A. Cole, M. W. Lark, A. J. Grodzinsky. Proteoglycan degradation after injurious compression of bovine and human articular cartilage in vitro: interaction with exogenous cytokines. Arthritis Rheum. 48:1292–1301, 2003
Quinn T. M., R. G. Allen, B. J. Schalet, P. Perumbuli, E. B. Hunziker. Matrix and cell injury due to sub-impact loading of adult bovine articular cartilage explants: effects of strain rate and peak stress. J. Orthop. Res. 19:242–249, 2001
Quinn T. M., A. J. Grodzinsky, E. B. Hunziker, J. D. Sandy. Effects of injurious compression on matrix turnover around individual cells in calf articular cartilage explants. J. Orthop. Res. 16:490–499, 1998
Radin E. L., I. L. Paul. Importance of bone in sparing articular cartilage from impact. Clin. Orthop. 78:342–344, 1971
Reddy G. K., C. S. Enwemeka. A simplified method for the analysis of hydroxyproline in biological tissues. Clin. Biochem. 29:225–229, 1996
Repo R. U., J. B. Finlay. Survival of articular cartilage after controlled impact. J. Bone Joint Surg. Am. 59:1068–1076, 1977
Sato T., K. Konomi, S. Yamasaki, S. Aratani, K. Tsuchimochi, M. Yokouchi, K. Masuko-Hongo, N. Yagishita, H. Nakamura, S. Komiya, M. Beppu, H. Aoki, K. Nishioka, T. Nakajima. Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage. Arthritis Rheum. 54:808–817, 2006
Scott C. C., K. A. Athanasiou. Design, validation, and utilization of an articular cartilage impact instrument. Proc. Inst. Mech. Eng. [H] 220:845–855, 2006
Smith R. L., D. R. Carter, D. J. Schurman. Pressure and shear differentially alter human articular chondrocyte metabolism: a review. Clin. Orthop. 427: S89–S95, 2004
Sweigart M. A., C. F. Zhu, D. M. Burt, P. D. DeHoll, C. M. Agrawal, T. O. Clanton, K. A. Athanasiou. Intraspecies and interspecies comparison of the compressive properties of the medial meniscus. Ann. Biomed. Eng. 32:1569–1579, 2004
Tchetverikov I., L. S. Lohmander, N. Verzijl, T. W. Huizinga, J. M. TeKoppele, R. Hanemaaijer, J. DeGroot. Mmp protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann. Rheum. Dis. 64:694–698, 2005
Torzilli P. A., R. Grigiene, J. Borrelli Jr., D. L. Helfet. Effect of impact load on articular cartilage: cell metabolism and viability, and matrix water content. J. Biomech. Eng. 121:433–441, 1999
Wilkins R. J., J. A. Browning, J. P. Urban. Chondrocyte regulation by mechanical load. Biorheology 37:67–74, 2000
Yagi R., D. McBurney, D. Laverty, S. Weiner, W. E. Horton Jr. Intrajoint comparisons of gene expression patterns in human osteoarthritis suggest a change in chondrocyte phenotype. J. Orthop. Res. 23:1128–1138, 2005
Acknowledgements
This study was supported, in part, by the U.S. Department of Transportation, National Highway Traffic Safety Administration Grant No. DTNH22-01-H-07551 and/or the Federal Highway Administration Grant No. FHWA ICRC(1) to the University of Alabama at Birmingham, Injury Control Research Center’s Southern Consortium for Injury Biomechanics. The authors would also like to acknowledge Chris Revell, Jerry Hu, and Todd Blumberg for their assistance.
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Natoli, R.M., Scott, C.C. & Athanasiou, K.A. Temporal Effects of Impact on Articular Cartilage Cell Death, Gene Expression, Matrix Biochemistry, and Biomechanics. Ann Biomed Eng 36, 780–792 (2008). https://doi.org/10.1007/s10439-008-9472-5
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DOI: https://doi.org/10.1007/s10439-008-9472-5