Skip to main content
Log in

Chondrocyte Differentiation is Modulated by Frequency and Duration of Cyclic Compressive Loading

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

Abstract

As part of a program of research aimed at determining the role of mechanical forces in connective tissue differentiation, we have developed a model for investigating the effects of dynamic compressive loading on chondrocyte differentiation in vitro. In the current study, we examined the influence of cyclic compressive loading of chick limb bud mesenchymal cells to a constant peak stress of 9.25 kPa during each of the first 3 days in culture. Cells embedded in agarose gel were subjected to uniaxial, cyclic compression at 0.03, 0.15, or 0.33 Hz for 2 h. In addition, load durations of 12, 54, or 120 min were evaluated while holding frequency constant at 0.33 Hz. For a 2 h duration, there was no response to loading at 0.03 Hz. A significant increase in chondrocyte differentiation was associated with loading at 0.15 Hz, and an even greater increase with loading at 0.33 Hz. Holding frequency constant at 0.33 Hz, a loading duration of 12 min elicited no response, whereas chondrocyte differentiation was enhanced by loading for either 54 or 120 min. Although not statistically significant from the 120 min response, average cartilage nodule density and glycosaminoglycan synthesis rate were highest in the 54 min duration group. This result suggests that cells may be sensitive to the level of cumulative (nonrecoverable) compressive strain, as well as to the dynamic strain history. © 2001 Biomedical Engineering Society.

PAC01: 8717-d, 8719Rr

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.

Similar content being viewed by others

References

  1. 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.28:1561–1569, 1995.

    Google Scholar 

  2. Buschmann, M. D., Y. A. Gluzband, A. J. Grodzinsky, and E. B. Hunziker. Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J. Cell. Sci.108:1497–1508, 1995.

    Google Scholar 

  3. Elder, S. H., J. H. Kimura, L. J. Soslowsky, M. Lavagnino, and S. A. Goldstein. Effects of compressive loading on chondrocyte differentiation in agarose cultures of chick limb bud cells. J. Orthop. Res.18:78–86, 2000.

    Google Scholar 

  4. Freeman, P. M., 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.

    Google Scholar 

  5. Hamburger, V., and H. Hamilton. A series of normal stages in development of the chick embryo. J. Morphol.88:49–92, 1951.

    Google Scholar 

  6. Hunziker, E. B., W. Herrmann, and R. K. Schenk. Improved cartilage fixation by ruthenium hexammine trichloride (RHT): A prerequisite for morphometry in growth cartilage. J. Ultrastruct. Res.81:1–12, 1982.

    Google Scholar 

  7. Kim, Y. J., R. L. Sah, A. J. Grodzinsky, A. H. Plaas, and J. D. Sandy. Mechanical regulation of cartilage biosynthetic behavior: Physical stimuli. Arch. Biochem. Biophys.311:1–12, 1994.

    Google Scholar 

  8. Kiraly, K., M. M. Hyttinen, J. J. Parkkinen, M. A. Arokoski, T. Lapvetelainen, K. Torronen, I. Kiviranta, and H. J. Helminen. Articular cartilage collagen birefringence is altered concurrent with changes in proteoglycan synthesis during dynamic in vitro loading. Anat. Rec.251:28–36, 1998.

    Google Scholar 

  9. Knight, M. M., D. A. Lee, and D. L. Bader. Distribution of chondrocyte deformation in compressed agarose gel using confocal microscopy. J. Cell. Eng. Incorp. Mol. Eng.1:97–102, 1996.

    Google Scholar 

  10. Larsson, T., R. M. Aspden, and D. Heinegard. Effects of mechanical load on cartilage matrix biosynthesis in vitro. Matrix11:388–394, 1991.

    Google Scholar 

  11. Lee, D. A., and D. L. Bader. Compressive strains at physiological frequencies influence the metabolism of chondrocytes seeded in agarose. J. Orthop. Res.15:181–188, 1997.

    Google Scholar 

  12. Martina, M., J. W. Mozrzymas, and F. Vittur. Membrane stretch activates a potassium channel in pig articular chondrocytes. Biochim. Biophys. Acta1329:205–210, 1997.

    Google Scholar 

  13. Palmoski, M. J., and K. D. Brandt. Effects of static and cyclic compressive loading on articular cartilage plugs in vitro. Arthritis Rheum.27:675–681, 1984.

    Google Scholar 

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

    Google Scholar 

  15. Steinmeyer, J., and S. Knue. The proteoglycan metabolism of mature articular cartilage explants superimposed to continuously applied cyclic mechanical loading. Biochem. Biophys. Res. Commun.240:216–221, 1997.

    Google Scholar 

  16. Takahashi, I., G. H. Nuckolls, K. Takahashi, O. Tanaka, I. Semba, R. Dashner, L. Shum, and H. C. Slavkin. Compressive force promotes sox9, type II collagen and aggrecan and inhibits IL-1beta expression resulting in chondrogenesis in mouse embryonic limb bud mesenchymal cells. J. Cell. Sci.111:2067–2076, 1998.

    Google Scholar 

  17. Takigawa, M., T. Takano, E. Shirai, and F. Suzuki. Cytoskeleton and differentiation: Effects of cytochalasin B and colchicine on expression of the differentiated phenotype of rabbit costal chondrocytes in culture. Cell Differ.14:197–204, 1984.

    Google Scholar 

  18. Torzilli, P. A., R. Grigiene, C. Huang, S. M. Friedman, S. B. Doty, A. L. Boskey, and G. Lust. Characterization of cartilage metabolic response to static and dynamic stress using a mechanical explant test system. J. Biomech.30:1–9, 1997.

    Google Scholar 

  19. Valhmu, W. B., E. J. Stazzone, N. M. Bachrach, F. Saed-Nejad, S. G. Fischer, V. C. Mow, and A. Ratcliffe. Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression. Arch. Biochem. Biophys.353:29–36, 1998.

    Google Scholar 

  20. van Kampen, G. P., G. H. Korver, and R. J. van de Stadt. Modulation of proteoglycan composition in cultured anatomically intact joint cartilage by cyclic loads of various magnitudes. Int. J. Tissue React.16:171–179, 1994.

    Google Scholar 

  21. 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.

    Google Scholar 

  22. Wright, M., P. Jobanputra, C. Bavington, D. M. Salter, and G. Nuki. Effects of intermittent pressure-induced strain on the electrophysiology of cultured human chondrocytes: Evidence for the presence of stretch-activated membrane ion channels. Clin. Sci.90:61–71, 1996.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Elder, S.H., Goldstein, S.A., Kimura, J.H. et al. Chondrocyte Differentiation is Modulated by Frequency and Duration of Cyclic Compressive Loading. Annals of Biomedical Engineering 29, 476–482 (2001). https://doi.org/10.1114/1.1376696

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1114/1.1376696

Navigation