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Solute Transport of Negatively Charged Contrast Agents Across Articular Surface of Injured Cartilage

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Abstract

Solute transport through the extracellular matrix (ECM) is crucial to chondrocyte metabolism. Cartilage injury affects solute transport in cartilage due to alterations in ECM structure and solute-matrix interactions. Therefore, cartilage injury may be detected by using contrast agent-based clinical imaging. In the present study, effects of mechanical injury on transport of negatively charged contrast agents in cartilage were characterized. Using cartilage plugs injured by mechanical compression protocol, effective partition coefficients and diffusion fluxes of iodine- and gadolinium-based contrast agents were measured using high resolution microCT imaging. For all contrast agents studied, effective diffusion fluxes increased significantly, particularly at early times during the diffusion process (38 and 33% increase after 4 min, P < 0.05 for iodine and Gd-DTPA; and 76% increase after 10 min for diatrizoate, P < 0.05). Effective partition coefficients were unaffected in mechanically injured cartilage. Mechanical injury reduced PG content and collagen integrity in cartilage superficial zone. This study suggests that alterations in contrast agent diffusion flux, a non-equilibrium transport parameter, provides a more sensitive indicator for assessment of cartilage matrix integrity than partition coefficient and the equilibrium distribution of solute. These findings may help in developing clinical methods of contrast agent-based imaging to detect cartilage injury.

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References

  1. Arokoski, J. P., M. M. Hyttinen, T. Lapvetelainen, P. Takacs, B. Kosztaczky, L. Modis, et al. Decreased birefringence of the superficial zone collagen network in the canine knee (stifle) articular cartilage after long distance running training, detected by quantitative polarised light microscopy. Ann. Rheum. Dis. 55:253–264, 1996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bansal, P. N., N. S. Joshi, V. Entezari, M. W. Grinstaff, and B. D. Snyder. Contrast enhanced computed tomography can predict the glycosaminoglycan content and biomechanical properties of articular cartilage. Osteoarthr. Cartil. 18:184–191, 2010.

    Article  CAS  PubMed  Google Scholar 

  3. Bashir, A., M. L. Gray, J. Hartke, and D. Burstein. Nondestructive imaging of human cartilage glycosaminoglycan concentration by MRI. Magn. Reson. Med. 41:857–865, 1999.

    Article  CAS  PubMed  Google Scholar 

  4. Chin, H. C., M. Moeini, and T. M. Quinn. Solute transport across the articular surface of injured cartilage. Arch. Biochem. Biophys. 535:241–247, 2013.

    Article  CAS  PubMed  Google Scholar 

  5. Choi, J. A., and G. E. Gold. MR imaging of articular cartilage physiology. Magn. Reson. Imaging Clin. N. Am. 19:249–282, 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Crema, M. D., F. W. Roemer, M. D. Marra, D. Burstein, G. E. Gold, F. Eckstein, et al. Articular cartilage in the knee: current MR imaging techniques and applications in clinical practice and research. Radiographics 31:37–61, 2011.

    Article  PubMed  Google Scholar 

  7. Evans, R. C., and T. M. Quinn. Solute diffusivity correlates with mechanical properties and matrix density of compressed articular cartilage. Arch. Biochem. Biophys. 442:1–10, 2005.

    Article  CAS  PubMed  Google Scholar 

  8. Flik, K. R., N. Verma, B. J. Cole, and R. R. Bach. Articular cartilage: structure, biology, and function. In: Cartilage Repair Strategies, edited by R. J. I. Williams. Totowa, NJ: Humana Press, 2007, pp. 1–12.

    Chapter  Google Scholar 

  9. Garcia, A. M., E. H. Frank, P. E. Grimshaw, and A. J. Grodzinsky. Contributions of fluid convection and electrical migration to transport in cartilage: relevance to loading. Arch. Biochem. Biophys. 333:317–325, 1996.

    Article  CAS  PubMed  Google Scholar 

  10. Hawezi, Z. K., E. Lammentausta, J. Svensson, L. E. Dahlberg, and C. J. Tiderius. In vivo transport of Gd-DTPA(2-) in human knee cartilage assessed by depth-wise dGEMRIC analysis. J. Magn. Reson. Imaging 34:1352–1358, 2011.

    Article  PubMed  Google Scholar 

  11. Jackson, A., and W. Gu. Transport properties of cartilaginous tissues. Curr. Rheumatol. Rev. 5:40, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Joshi, N. S., P. N. Bansal, R. C. Stewart, B. D. Snyder, and M. W. Grinstaff. Effect of contrast agent charge on visualization of articular cartilage using computed tomography: exploiting electrostatic interactions for improved sensitivity. J. Am. Chem. Soc. 131:13234–13235, 2009.

    Article  CAS  PubMed  Google Scholar 

  13. Kallioniemi, A. S., J. S. Jurvelin, M. T. Nieminen, M. J. Lammi, and J. Töyräs. Contrast agent enhanced pQCT of articular cartilage. Phys. Med. Biol. 52:1209–1219, 2007.

    Article  CAS  PubMed  Google Scholar 

  14. Kiraly, K., T. Lapvetelainen, J. Arokoski, K. Torronen, L. Modis, I. Kiviranta, et al. Application of selected cationic dyes for the semiquantitative estimation of glycosaminoglycans in histological sections of articular cartilage by microspectrophotometry. Histochem. J. 28:577–590, 1996.

    Article  CAS  PubMed  Google Scholar 

  15. Kokkonen, H. T., A. S. Aula, H. Kröger, J. S. Suomalainen, E. Lammentausta, E. Mervaala, J. S. Jurvelin, and J. Töyräs. Delayed computed tomography arthrography of human knee cartilage in vivo. Cartilage 3(4):334–341, 2012.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kokkonen, H. T., J. S. Jurvelin, V. Tiitu, and J. Töyräs. Detection of mechanical injury of articular cartilage using contrast enhanced computed tomography. Osteoarthr. Cartil. 19:295–301, 2011.

    Article  CAS  PubMed  Google Scholar 

  17. Kokkonen, H. T., J. S. Suomalainen, A. Joukainen, H. Kröger, J. Sirola, J. S. Jurvelin, J. Salo, and J. Töyräs. In vivo diagnostics of human knee cartilage lesions using delayed CBCT arthrography. J. Orthop. Res. 32(3):403–412, 2014.

    Article  PubMed  Google Scholar 

  18. Krause, W., and P. W. Schneider. Chemisry of X-Ray Contrast Agents: Contrast Agents II. Berlin: Springer, pp. 107–150, 2002.

    Google Scholar 

  19. Kulmala, K. A., R. K. Korhonen, P. Julkunen, J. S. Jurvelin, T. M. Quinn, H. Kroger, et al. Diffusion coefficients of articular cartilage for different CT and MRI contrast agents. Med. Eng. Phys. 32:878–882, 2010.

    Article  CAS  PubMed  Google Scholar 

  20. Kurz, B., M. Jin, P. Patwari, D. M. Cheng, M. W. Lark, and A. J. Grodzinsky. Biosynthetic response and mechanical properties of articular cartilage after injurious compression. J. Orthop. Res. 19:1140–1146, 2001.

    Article  CAS  PubMed  Google Scholar 

  21. Lu, X. L., and V. C. Mow. Biomechanics of articular cartilage and determination of material properties. Med. Sci. Sports Exerc. 40:193–199, 2008.

    Article  PubMed  Google Scholar 

  22. Maroudas, A. Biophysical chemistry of cartilaginous tissues with special reference to solute and fluid transport. Biorheology 12:233–248, 1975.

    CAS  PubMed  Google Scholar 

  23. Maroudas, A. Transport of solutes through cartilage: permeability to large molecules. J. Anat. 122:335–347, 1976.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. McKenzie, C. A., A. Williams, P. V. Prasad, and D. Burstein. Three-dimensional delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at 1.5T and 3.0T. J. Magn. Reson. Imaging 24:928–933, 2006.

    Article  PubMed  Google Scholar 

  25. Morel, V., C. Berutto, and T. M. Quinn. Effects of damage in the articular surface on the cartilage response to injurious compression in vitro. J. Biomech. 39:924–930, 2006.

    Article  CAS  PubMed  Google Scholar 

  26. Morel, V., and T. M. Quinn. Cartilage injury by ramp compression near the gel diffusion rate. J. Orthop. Res. 22:145–151, 2004.

    Article  PubMed  Google Scholar 

  27. Morel, V., and T. M. Quinn. Short-term changes in cell and matrix damage following mechanical injury of articular cartilage samples and modelling of microphysical mediators. Biorheology 41:509–519, 2004.

    CAS  PubMed  Google Scholar 

  28. Palmer, A. W., R. E. Guldberg, and M. E. Levenston. Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography. Proc. Natl. Acad. Sci. USA 103:19255–19269, 2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pan, J., X. Zhou, W. Li, J. E. Novotny, S. B. Doty, and L. Wang. In situ measurement of transport between subchondral bone and articular cartilage. J. Orthop. Res. 27(10):1347–1352, 2009.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Pearle, A. D., R. F. Warren, and S. A. Rodeo. Basic science of articular cartilage and osteoarthritis. Clin. Sports Med. 24:1–12, 2005.

    Article  PubMed  Google Scholar 

  31. Quinn, T. M., R. G. Allen, B. J. Schalet, P. Perumbuli, and E. B. Hunziker. Matrix and cell injury due to sub-impact loading of adult bovine articular cartilage samples: effects of strain rate and peak stress. J. Orthop. Res. 19:242–249, 2001.

    Article  CAS  PubMed  Google Scholar 

  32. Rieppo, J., J. Hallikainen, J. S. Jurvelin, I. Kiviranta, H. J. Helminen, and M. M. Hyttinen. Practical considerations in the use of polarized light microscopy in the analysis of the collagen network in articular cartilage. Microsc. Res. Tech. 71:279–287, 2008.

    Article  PubMed  Google Scholar 

  33. Salo, E. N., M. J. Nissi, K. A. Kulmala, V. Tiitu, J. Töyräs, and M. T. Nieminen. Diffusion of Gd-DTPA(2)(-) into articular cartilage. Osteoarthr. Cartil. 20:117–126, 2012.

    Article  PubMed  Google Scholar 

  34. Samosky, J. T., D. Burstein, W. Eric Grimson, R. Howe, S. Martin, and M. L. Gray. Spatially-localized correlation of dGEMRIC-measured GAG distribution and mechanical stiffness in the human tibial plateau. J. Orthop. Res. 23:93–101, 2005.

    Article  CAS  PubMed  Google Scholar 

  35. Silvast, T. S., H. T. Kokkonen, J. S. Jurvelin, T. M. Quinn, M. T. Nieminen, and J. Töyräs. Diffusion and near-equilibrium distribution of MRI and CT contrast agents in articular cartilage. Phys. Med. Biol. 54:6823–6836, 2009.

    Article  PubMed  Google Scholar 

  36. Stockwell, R. A. Biology of the Cartilage Cells. Cambridge: Cambridge University Press, 1979.

    Google Scholar 

  37. Tiderius, C. J., L. E. Olsson, P. Leander, O. Ekberg, and L. Dahlberg. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) in early knee osteoarthritis. Magn. Reson. Med. 49:488–492, 2003.

    Article  PubMed  Google Scholar 

  38. Torzilli, P. A., J. M. Arduino, J. D. Gregory, and M. Bansal. Effect of proteoglycan removal on solute mobility in articular cartilage. J. Biomech. 30:895–902, 1997.

    Article  CAS  PubMed  Google Scholar 

  39. Verteramo, A., and B. B. Seedhom. Effect of a single impact loading on the structure and mechanical properties of articular cartilage. J. Biomech. 40:3580–3589, 2007.

    Article  CAS  PubMed  Google Scholar 

  40. Wayne, J. S., K. A. Kraft, K. J. Shields, C. Yin, J. R. Owen, and D. G. Disler. MR imaging of normal and matrix-depleted cartilage: correlation with biomechanical function and biochemical composition. Radiology 228:493–499, 2003.

    Article  PubMed  Google Scholar 

  41. Xie, L., A. S. Lin, R. E. Guldberg, and M. E. Levenston. Nondestructive assessment of sGAG content and distribution in normal and degraded rat articular cartilage via EPIC-microCT. Osteoarthr. Cartil. 18:65–72, 2010.

    Article  CAS  PubMed  Google Scholar 

  42. Yoo, H. J., S. H. Hong, J. Y. Choi, I. J. Lee, S. J. Kim, J. A. Choi, et al. Contrast-enhanced CT of articular cartilage: experimental study for quantification of glycosaminoglycan content in articular cartilage. Radiology 261:805–812, 2011.

    Article  PubMed  Google Scholar 

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Acknowledgments

Academy of Finland is acknowledged for funding (Decision Number 269315).

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Correspondence to H. T. Kokkonen.

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Associate Editor Karol Miller oversaw the review of this article.

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Kokkonen, H.T., Chin, H.C., Töyräs, J. et al. Solute Transport of Negatively Charged Contrast Agents Across Articular Surface of Injured Cartilage. Ann Biomed Eng 45, 973–981 (2017). https://doi.org/10.1007/s10439-016-1756-6

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  • DOI: https://doi.org/10.1007/s10439-016-1756-6

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