Skip to main content
Log in

Chondrocyte Deformations Under Mild Dynamic Loading Conditions

  • Original Article
  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Dynamic deformation of chondrocytes are associated with cell mechanotransduction and thus may offer a new understanding of the mechanobiology of articular cartilage. Despite extensive research on chondrocyte deformations for static conditions, work for dynamic conditions remains rare. However, it is these dynamic conditions that articular cartilage in joints are exposed to everyday, and that seem to promote biological signaling in chondrocytes. Therefore, the objective of this study was to develop an experimental technique to determine the in situ deformations of chondrocytes when the cartilage is dynamically compressed. We hypothesized that dynamic deformations of chondrocytes vastly differ from those observed under steady-state static strain conditions. Real-time chondrocyte geometry was reconstructed at 10, 15, and 20% compression during ramp compressions with 20% ultimate strain, applied at a strain rate of 0.2% s−1, followed by stress relaxation. Dynamic compressive chondrocyte deformations were non-linear as a function of nominal strain, with large deformations in the early and small deformations in the late part of compression. Early compression (up to about 10%) was associated with chondrocyte volume loss, while late compression (> ~ 10%) was associated with cell deformation but minimal volume loss. Force continued to decrease for 5 min in the stress-relaxation phase, while chondrocyte shape/volume remained unaltered after the first minute of stress-relaxation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Abusara, Z., R. Krawetz, B. Steele, M. DuVall, T. Schmidt, and W. Herzog. Muscular loading of joints triggers cellular secretion of PRG4 into the joint fluid. J. Biomech. 46:1225–1230, 2013.

    CAS  PubMed  Google Scholar 

  2. Abusara, Z., R. Seerattan, A. Leumann, R. Thompson, and W. Herzog. A novel method for determining articular cartilage chondrocyte mechanics in vivo. J. Biomech. 44:930–934, 2011.

    CAS  PubMed  Google Scholar 

  3. Ashwell, M. S., M. G. Gonda, K. Gray, C. Maltecca, A. T. O’Nan, J. P. Cassady, and P. L. Mente. Changes in chondrocyte gene expression following in vitro impaction of porcine articular cartilage in an impact injury model. J. Orthop. Res. 31:385–391, 2013.

    CAS  PubMed  Google Scholar 

  4. Bachrach, N. M., W. B. Valhmu, E. Stazzone, A. Ratcliffe, W. M. Lai, and V. C. Mow. Changes in proteoglycan synthesis of chondrocytes in articular cartilage are associated with the time-dependent changes in their mechanical environment. J. Biomech. 1995. https://doi.org/10.1016/0021-9290(95)00103-4.

    Article  PubMed  Google Scholar 

  5. Bayliss, M. T., M. Venn, A. Maroudas, and S. Y. Ali. Structure of proteoglycans from different layers of human articular cartilage. Biochem. J. 209:387–400, 1983.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Ben-Ze’ve, A. Animal cell shape changes and gene expression. BioEssays 13:207–212, 1991.

    Google Scholar 

  7. Berg, J., J. Tymoczko, and L. Stryer. Cells can respond to changes in their environments. In: Biochemistry. New York: W H Freeman, 2002. https://www.ncbi.nlm.nih.gov/books/NBK22568/

  8. Bhargavi, K., and S. Jyothi. A survey on threshold based segmentation technique in image processing. Int. J. Innov. Res. Dev. 3:234–239, 2014.

    Google Scholar 

  9. Bleuel, J., F. Zaucke, G. P. Brüggemann, and A. Niehoff. Effects of cyclic tensile strain on chondrocyte metabolism: a systematic review. PLoS ONE 10:e0119816, 2015.

    PubMed  PubMed Central  Google Scholar 

  10. Bush, P. G., and A. C. Hall. The volume and morphology of chondrocytes within non-degenerate and degenerate human articular cartilage. Osteoarthr. Cartil. 11:242–251, 2003.

    CAS  Google Scholar 

  11. Chan, P. S., A. E. Schlueter, P. M. Coussens, G. J. M. Rosa, R. C. Haut, and M. W. Orth. Gene expression profile of mechanically impacted bovine articular cartilage explants. J. Orthop. Res. 23:1146–1151, 2005.

    CAS  PubMed  Google Scholar 

  12. Chen, A. C. C., W. C. C. Bae, R. M. M. Schinagl, and R. L. L. Sah. Depth- and strain-dependent mechanical and electromechanical properties of full-thickness bovine articular cartilage in confined compression. J. Biomech. 34:1–12, 2001.

    CAS  PubMed  Google Scholar 

  13. Chen, S. S., Y. H. Falcovitz, R. Schneiderman, A. Maroudas, and R. L. Sah. Depth-dependent compressive properties of normal aged human femoral head articular cartilage: relationship to fixed charge density. Osteoarthr. Cartil. 9:561–569, 2001.

    CAS  Google Scholar 

  14. Cho, H. J., H. J. Chun, E. S. Kim, and B. R. Cho. Multiphoton microscopy: an introduction to gastroenterologists. World J. Gastroenterol. 2011. https://doi.org/10.3748/wjg.v17.i40.4456.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Choi, J. B., I. Youn, L. Cao, H. A. Leddy, C. L. Gilchrist, L. A. Setton, and F. Guilak. Zonal changes in the three-dimensional morphology of the chondron under compression: the relationship among cellular, pericellular, and extracellular deformation in articular cartilage. J. Biomech. 40:2596–2603, 2007.

    PubMed  PubMed Central  Google Scholar 

  16. Davisson, T., S. Kunig, A. Chen, R. Sah, and A. Ratcliffe. Static and dynamic compression modulate matrix metabolism in tissue engineered cartilage. J. Orthop. Res. 20:842–848, 2002.

    CAS  PubMed  Google Scholar 

  17. de Vries, S. A. H., M. C. van Turnhout, C. W. J. Oomens, A. Erdemir, K. Ito, and C. C. van Donkelaar. Deformation thresholds for chondrocyte death and the protective effect of the pericellular matrix. Tissue Eng. Part A 20:1–7, 2014.

    Google Scholar 

  18. Démarteau, O., D. Wendt, A. Braccini, M. Jakob, D. Schäfer, M. Heberer, and I. Martin. Dynamic compression of cartilage constructs engineered from expanded human articular chondrocytes. Biochem. Biophys. Res. Commun. 310:580–588, 2003.

    PubMed  Google Scholar 

  19. Espino, D. M., D. E. T. Shepherd, and D. W. L. Hukins. Viscoelastic properties of bovine knee joint articular cartilage: dependency on thickness and loading frequency. BMC Musculoskelet. Disord. 15:205, 2014.

    PubMed  PubMed Central  Google Scholar 

  20. Federico, S., and A. Grillo. Elasticity and permeability of porous fibre-reinforced materials under large deformations. Mech. Mater. 44:58–71, 2012.

    Google Scholar 

  21. Fick, J. M., A. Ronkainen, W. Herzog, and R. K. Korhonen. Site-dependent biomechanical responses of chondrocytes in the rabbit knee joint. J. Biomech. 48:4010–4019, 2015.

    CAS  PubMed  Google Scholar 

  22. Freeman, P. M., R. N. Natarajan, J. H. Kimura, and T. P. Andriacchi. Chondrocyte cells respond mechanically to compressive loads. J. Orthop. Res. 12:311–320, 1994.

    CAS  PubMed  Google Scholar 

  23. Fulcher, G. R., D. W. L. Hukins, and D. E. T. Shepherd. Viscoelastic properties of bovine articular cartilage attached to subchondral bone at high frequencies. BMC Musculoskelet. Disord. 10:61, 2009.

    PubMed  PubMed Central  Google Scholar 

  24. Guilak, F. Volume and surface area measurement of viable chondrocytes in situ using geometric modelling of serial confocal sections. J. Microsc. 173:245–256, 1994.

    CAS  PubMed  Google Scholar 

  25. Guilak, F. Compression-induced changes in the shape and volume of the chondrocyte nucleus. J. Biomech. 28:1529–1541, 1995.

    CAS  PubMed  Google Scholar 

  26. Guilak, F., A. Ratcliffe, and V. C. Mow. Chondrocyte deformation and local tissue strain in articular cartilage: a confocal microscopy study. J. Orthop. Res. 13:410–421, 1995.

    CAS  PubMed  Google Scholar 

  27. Hall, A. C. The role of chondrocyte morphology and volume in controlling phenotype—implications for osteoarthritis, cartilage repair, and cartilage engineering. Curr. Rheumatol. Rep. 21(8):38, 2019.

    PubMed  PubMed Central  Google Scholar 

  28. Han, S.-K., P. Colarusso, and W. Herzog. Confocal microscopy indentation system for studying in situ chondrocyte mechanics. Med. Eng. Phys. 31:1038–1042, 2009.

    PubMed  Google Scholar 

  29. Han, S.-K., A. P. Ronkainen, S. Saarakkala, L. Rieppo, W. Herzog, and R. K. Korhonen. Alterations in structural macromolecules and chondrocyte deformations in lapine retropatellar cartilage 9 weeks after anterior cruciate ligament transection. J. Orthop. Res. 36:342–350, 2017.

    PubMed  Google Scholar 

  30. Han, S., R. Seerattan, and W. Herzog. Mechanical loading of in situ chondrocytes in lapine retropatellar cartilage after anterior cruciate ligament transection. J. R. Soc. Interface 7:895–903, 2010.

    PubMed  Google Scholar 

  31. Kääb, M. J., R. G. Richards, K. Ito, I. Ap Gwynn, and H. P. Nötzli. Deformation of chondrocytes in articular cartilage under compressive load: a morphological study. Cells. Tissues. Organs 175:133–139, 2003.

    PubMed  Google Scholar 

  32. Kisiday, J. D., M. Jin, M. A. DiMicco, B. Kurz, and A. J. Grodzinsky. Effects of dynamic compressive loading on chondrocyte biosynthesis in self-assembling peptide scaffolds. J. Biomech. 37:595–604, 2004.

    PubMed  Google Scholar 

  33. Knight, M. M., S. A. Ghori, D. A. Lee, and D. L. Bader. Measurement of the deformation of isolated chondrocytes in agarose subjected to cyclic compression. Med. Eng. Phys. 20:684–688, 1998.

    CAS  PubMed  Google Scholar 

  34. Komeili, A., Z. Abusara, S. Federico, and W. Herzog. Effect of strain rate on transient local strain variations in articular cartilage. JMBBM, 2018.

  35. Komeili, A., Z. Abusara, S. Federico, and W. Herzog. A compression system for studying depth dependent mechanical properties of articular cartilage under dynamic loading conditions. Med. Eng. Phys. 60:103–108, 2018.

    PubMed  Google Scholar 

  36. Komeili, A., W. Chau, and W. Herzog. Effects of macro-cracks on the load bearing capacity of articular cartilage. Biomech. Model. Mechanobiol. 18:1371–1381, 2019.

    PubMed  Google Scholar 

  37. Korhonen, R. K., and W. Herzog. Depth-dependent analysis of the role of collagen fibrils, fixed charges and fluid in the pericellular matrix of articular cartilage on chondrocyte mechanics. J. Biomech. 41:480–485, 2008.

    PubMed  Google Scholar 

  38. Lee, D. A., M. M. Knight, J. F. Bolton, B. D. Idowu, M. V. Kayser, and D. L. Bader. Chondrocyte deformation within compressed agarose constructs at the cellular and sub-cellular levels. J. Biomech. 33:81–95, 2000.

    CAS  PubMed  Google Scholar 

  39. Leong, D. J., J. A. Hardin, N. J. Cobelli, and H. B. Sun. Mechanotransduction and cartilage integrity. Ann. N. Y. Acad. Sci. 1240:32–37, 2011.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Liu, Q., X. Hu, X. Zhang, X. Duan, P. Yang, F. Zhao, and Y. Ao. Effects of mechanical stress on chondrocyte phenotype and chondrocyte extracellular matrix expression. Sci. Rep. 6:1–8, 2016.

    Google Scholar 

  41. Liu, F., M. Kozanek, A. Hosseini, S. K. Van de Velde, T. J. Gill, H. E. Rubash, and G. Li. In vivo tibiofemoral cartilage deformation during the stance phase of gait. J. Biomech. 43:658–665, 2010.

    PubMed  Google Scholar 

  42. Madden, R., S.-K. Han, and W. Herzog. Chondrocyte deformation under extreme tissue strain in two regions of the rabbit knee joint. J. Biomech. 46:554–560, 2013.

    PubMed  Google Scholar 

  43. Madden, R. M. J., S.-K. K. Han, and W. Herzog. The effect of compressive loading magnitude on in situ chondrocyte calcium signaling. Biomech. Model. Mechanobiol. 14:135–142, 2014.

    PubMed  PubMed Central  Google Scholar 

  44. Maroudas, A. I. Balance between swelling pressure and collagen tension in normal and degenerate cartilage. Nature 260:808–809, 1976.

    CAS  PubMed  Google Scholar 

  45. Maroudas, A., and P. Bullough. Permeability of articular cartilage. Nature 219:1260–1261, 1968.

    CAS  PubMed  Google Scholar 

  46. Mauck, R. L., S. B. Nicoll, S. L. Seyhan, G. A. Ateshian, and C. T. Hung. Synergistic action of growth factors and dynamic loading for articular cartilage tissue engineering. Tissue Eng. 9:597–611, 2003.

    CAS  PubMed  Google Scholar 

  47. Mauck, R. L., S. L. Seyhan, G. A. Ateshian, and C. T. Hung. Influence of seeding density and dynamic deformational loading on the developing structure/function relationships of chondrocyte-seeded agarose hydrogels. Ann. Biomed. Eng. 30:1046–1056, 2002.

    PubMed  Google Scholar 

  48. Mauck, R. L., M. A. Soltz, C. C. Wang, D. D. Wong, P. H. Chao, W. B. Valhmu, C. T. Hung, and G. A. Ateshian. Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J. Biomech. Eng. 122:252–260, 2000.

    CAS  PubMed  Google Scholar 

  49. McNulty, A. L., H. A. Leddy, W. Liedtke, and F. Guilak. TRPV4 as a therapeutic target for joint diseases. Naunyn Schmiedebergs Arch. Pharmacol. 388:437–450, 2015.

    CAS  PubMed  Google Scholar 

  50. Moo, E. K., Z. Abusara, N. A. Abu Osman, B. Pingguan-Murphy, and W. Herzog. Dual photon excitation microscopy and image threshold segmentation in live cell imaging during compression testing. J. Biomech. 46:2024–2031, 2013.

    PubMed  Google Scholar 

  51. Moo, E. K., and W. Herzog. Unfolding of membrane ruffles of in situ chondrocytes under compressive loads. J. Orthop. Res. 35:304–310, 2017.

    CAS  PubMed  Google Scholar 

  52. Mow, V. C., and F. Guilak. Deformation of chondrocytes within the extracellular matrix of articular cartilage. In: Tissue Engineering. Boston: Birkhäuser, 1993, pp. 128–145. https://doi.org/10.1007/978-1-4615-8186-4_13.

  53. Mow, V. C., S. C. Kuei, W. M. Lai, and C. G. Armstrong. Biphasic creep and stress relaxation of articular cartilage in compression? Theory and experiments. J. Biomech. Eng. 102:73–84, 1980.

    CAS  PubMed  Google Scholar 

  54. Nam, J., B. D. Aguda, B. Rath, and S. Agarwal. Biomechanical thresholds regulate inflammation through the NF-kappaB pathway: experiments and modeling. PLoS ONE 4:e5262, 2009.

    PubMed  PubMed Central  Google Scholar 

  55. Ng, K. W., R. L. Mauck, C. C.-B. Wang, T.-A. N. Kelly, M. M.-Y. Ho, F. H. Chen, G. A. Ateshian, and C. T. Hung. Duty cycle of deformational loading influences the growth of engineered articular cartilage. Cell Mol. Bioeng. 2:386–394, 2009.

    PubMed  PubMed Central  Google Scholar 

  56. Park, S., C. T. Hung, and G. A. Ateshian. Mechanical response of bovine articular cartilage under dynamic unconfined compression loading at physiological stress levels. Osteoarthr. Cartil. 12:65–73, 2004.

    CAS  Google Scholar 

  57. Ramage, L., G. Nuki, and D. M. Salter. Signalling cascades in mechanotransduction: cell-matrix interactions and mechanical loading. Scand. J. Med. Sci. Sports 19:457–469, 2009.

    CAS  PubMed  Google Scholar 

  58. Sachs, F. Stretch-activated ion channels: what are they? Physiology 25:50–56, 2010.

    CAS  PubMed  Google Scholar 

  59. Sah, R. L.-Y., Y.-J. Kim, J.-Y. H. Doong, A. J. Grodzinsky, A. H. K. Plass, and J. D. Sandy. Biosynthetic response of cartilage explants to dynamic compression. J. Orthop. Res. 7:619–636, 1989.

    CAS  PubMed  Google Scholar 

  60. Sanchez-Adams, J., H. A. Leddy, A. L. McNulty, C. J. O’Conor, and F. Guilak. The mechanobiology of articular cartilage: bearing the burden of osteoarthritis. Curr. Rheumatol. Rep. 16(10):451, 2014.

    PubMed  PubMed Central  Google Scholar 

  61. Schinagl, R. M., D. Gurskis, A. C. Chen, and R. L. Sah. Depth-dependent confined compression modulus of full-thickness bovine articular cartilage. J. Orthop. Res. 15:499–506, 1997.

    CAS  PubMed  Google Scholar 

  62. Sibole, S. C. pyCellAnalyst: extensive software for three-dimensional analysis of deforming cells. 216AD. https://doi.org/10.11575/PRISM/27488.

  63. Sibole, S. C., and A. Erdemir. Chondrocyte deformations as a function of tibiofemoral joint loading predicted by a generalized high-throughput pipeline of multi-scale simulations. PLoS ONE 7:1–13, 2012.

    Google Scholar 

  64. Szafranski, J. D., A. J. Grodzinsky, E. Burger, V. Gaschen, H. H. Hung, and E. B. Hunziker. Chondrocyte mechanotransduction: effects of compression on deformation of intracellular organelles and relevance to cellular biosynthesis. Osteoarthr. Cartil. 12:937–946, 2004.

    Google Scholar 

  65. Thambyah, A., and N. Broom. On how degeneration influences load-bearing in the cartilage–bone system: a microstructural and micromechanical study. Osteoarthr. Cartil. 15:1410–1423, 2007.

    CAS  Google Scholar 

  66. Tomic, A., A. Grillo, and S. Federico. Poroelastic materials reinforced by statistically oriented fibres–numerical implementation and application to articular cartilage. IMA J. Appl. Math. 79:1027–1059, 2014.

    Google Scholar 

  67. Trickey, W. R., G. M. Lee, and F. Guilak. Viscoelastic properties of chondrocytes from normal and osteoarthritic human cartilage. J. Orthop. Res. 18:891–898, 2000.

    CAS  PubMed  Google Scholar 

  68. Wong, M., M. Siegrist, and X. Cao. Cyclic compression of articular cartilage explants is associated with progressive consolidation and altered expression pattern of extracellular matrix proteins. Matrix Biol. 18:391–399, 1999.

    CAS  PubMed  Google Scholar 

  69. Wong, M., P. Wuethrich, M. D. Buschmann, P. Eggli, and E. Hunziker. Chondrocyte biosynthesis correlates with local tissue strain in statically compressed adult articular cartilage. J. Orthop. Res. 15:189–196, 1997.

    CAS  PubMed  Google Scholar 

  70. Youn, I., J. B. Choi, L. Cao, L. A. Setton, and F. Guilak. Zonal variations in the three-dimensional morphology of the chondron measured in situ using confocal microscopy. Osteoarthr. Cartil. 14:889–897, 2006.

    CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by The Canada Research Chair Programme for Molecular and Cellular Biomechanics [Grant Number 950-230603, 2015], The Canadian Institutes of Health Research (CIHR) Foundation scheme grant [Grant Number MOP-111205, 2015], The Killam Foundation, and Alberta Innovates Health Solutions [Award Number 201610102, 2016]. The authors have no competing interests to declare. This work was carried out in accordance with the University of Calgary guidelines with ethical approve AC18-0082.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Walter Herzog.

Additional information

Associate Editor Michael S. Detamore oversaw the review of this article.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Komeili, A., Otoo, B.S., Abusara, Z. et al. Chondrocyte Deformations Under Mild Dynamic Loading Conditions. Ann Biomed Eng 49, 846–857 (2021). https://doi.org/10.1007/s10439-020-02615-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-020-02615-9

Keywords

Navigation