Skip to main content

Advertisement

SpringerLink
Log in

Inbred Strain-Specific Effects of Exercise in Wild Type and Biglycan Deficient Mice

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

Abstract

Biglycan (bgn)-deficient mice (KO) have defective osteoblasts which lead to changes in the amount and quality of bone. Altered tissue strength in C57BL6/129 (B6;129) KO mice, a property which is independent of tissue quantity, suggests that deficiencies in tissue quality are responsible. However, the response to bgn-deficiency is inbred strain-specific. Mechanical loading influences bone matrix quality in addition to any increase in bone mass or change in bone formation activity. Since many diseases influence the mechanical integrity of bone through altered tissue quality, loading may be a way to prevent and treat extracellular matrix deficiencies. C3H/He (C3H) mice consistently have a less vigorous response to mechanical loading vs. other inbred strains. It was therefore hypothesized that the bones from both wild type (WT) and KO B6;129 mice would be more responsive to exercise than the bones from C3H mice. To test these hypotheses at 11 weeks of age, following 21 consecutive days of exercise, we investigated cross-sectional geometry, mechanical properties, and tissue composition in the tibiae of male mice bred on B6;129 and C3H backgrounds. This study demonstrated inbred strain-specific compositional and mechanical changes following exercise in WT and KO mice, and showed evidence of genotype-specific changes in bone in response to loading in a gene disruption model. This study further shows that exercise can influence bone tissue composition and/or mechanical integrity without changes in bone geometry. Together, these data suggest that exercise may represent a possible means to alter tissue quality and mechanical deficiencies caused by many diseases of bone.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

References

  1. Adami, S., D. Gatti, V. Braga, D. Bianchini, and M. Rossini. Site-specific effects of strength training on bone structure and geometry of ultradistal radius in postmenopausal women. J. Bone Miner. Res. 14:120–124, 1999.

    Article  CAS  PubMed  Google Scholar 

  2. Akhter, M. P., D. M. Cullen, E. A. Pedersen, D. B. Kimmel, and R. R. Recker. Bone response to in vivo mechanical loading in two breeds of mice. Calcif. Tissue Int. 63:442–449, 1998.

    Article  CAS  PubMed  Google Scholar 

  3. Amblard, D., M. H. Lafage-Proust, A. Laib, T. Thomas, P. Ruegsegger, C. Alexandre, and L. Vico. Tail suspension induces bone loss in skeletally mature mice in the C57BL/6J strain but not in the C3H/HeJ strain. J. Bone Miner. Res. 18:561–569, 2003.

    Article  PubMed  Google Scholar 

  4. Ameye, L., D. Aria, K. Jepsen, A. Oldberg, T. Xu, and M. F. Young. Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice leads to gait impairment, ectopic ossification, and osteoarthritis. FASEB J. 16:673–680, 2002.

    Article  CAS  PubMed  Google Scholar 

  5. Baig, A., J. Fox, R. Young, Z. Wang, J. Hsu, W. Higuchi, A. Chhettry, H. Zhuang, and M. Otsuka. Relationships among carbonated apatite solubility, crystallite size, and microstrain parameters. Calcif. Tissue Int. 64:437–449, 1999.

    Article  CAS  PubMed  Google Scholar 

  6. Bhowmik, R., K. S. Katti, and D. R. Katti. Mechanics of molecular collagen is influenced by hydroxyapatite in natural bone. J. Mater. Sci. 42:8795–8803, 2007.

    Article  CAS  Google Scholar 

  7. Bianco, P., L. W. Fisher, M. F. Young, J. D. Termine, and P. G. Robey. Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues. J. Histochem. Cytochem. 38:1549–1563, 1990.

    CAS  PubMed  Google Scholar 

  8. Boskey, A. L., T. M. Wright, and R. D. Blank. Collagen and bone strength. J. Bone Miner. Res. 14:330–335, 1999.

    Article  CAS  PubMed  Google Scholar 

  9. Burger, E. H., and J. Klein-Nulend. Mechanotransduction in bone–role of the lacuno-canalicular network. FASEB J. 13(Suppl):S101–S112, 1999.

    CAS  PubMed  Google Scholar 

  10. Burstein, A. H., J. M. Zika, K. G. Heiple, and L. Klein. Contribution of collagen and mineral to the elastic-plastic properties of bone. J. Bone Joint Surg. Am. 57:956–961, 1975.

    CAS  PubMed  Google Scholar 

  11. Carden, A., R. M. Rajachar, M. D. Morris, and D. H. Kohn. Ultrastructural changes accompanying the mechanical deformation of bone tissue: a Raman imaging study. Calcif. Tissue Int. 72:166–175, 2003.

    Article  CAS  PubMed  Google Scholar 

  12. Chen, X. D., M. R. Allen, S. Bloomfield, T. Xu, and M. Young. Biglycan-deficient mice have delayed osteogenesis after marrow ablation. Calcif. Tissue Int. 72:577–582, 2003.

    Article  CAS  PubMed  Google Scholar 

  13. Chen, X. D., L. W. Fisher, P. G. Robey, and M. F. Young. The small leucine-rich proteoglycan biglycan modulates BMP-4-induced osteoblast differentiation. FASEB J. 18:948–958, 2004.

    Article  CAS  PubMed  Google Scholar 

  14. Chen, X. D., S. Shi, T. Xu, P. G. Robey, and M. F. Young. Age-related osteoporosis in biglycan-deficient mice is related to defects in bone marrow stromal cells. J. Bone Miner. Res. 17:331–340, 2002.

    Article  CAS  PubMed  Google Scholar 

  15. Corsi, A., T. Xu, X. D. Chen, A. Boyde, J. Liang, M. Mankani, B. Sommer, R. V. Iozzo, I. Eichstetter, P. G. Robey, P. Bianco, and M. F. Young. Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues. J. Bone Miner. Res. 17:1180–1189, 2002.

    Article  CAS  PubMed  Google Scholar 

  16. Duncan, R. L., and C. H. Turner. Mechanotransduction and the functional response of bone to mechanical strain. Calcif. Tissue Int. 57:344–358, 1995.

    Article  CAS  PubMed  Google Scholar 

  17. Follet, H., G. Boivin, C. Rumelhart, and P. J. Meunier. The degree of mineralization is a determinant of bone strength: a study on human calcanei. Bone 34:783–789, 2004.

    Article  CAS  PubMed  Google Scholar 

  18. Fritsch, A., C. Hellmich, and L. Dormieux. Ductile sliding between mineral crystals followed by rupture of collagen crosslinks: experimentally supported micromechanical explanation of bone strength. J. Theor. Biol. 260:230–252, 2009.

    Article  CAS  PubMed  Google Scholar 

  19. Hoshi, A., H. Watanabe, M. Chiba, and Y. Inaba. Bone density and mechanical properties in femoral bone of swim loaded aged mice. Biomed. Environ. Sci. 11:243–250, 1998.

    CAS  PubMed  Google Scholar 

  20. Isaksson, H., V. Tolvanen, M. A. J. Finnilä, J. Iivarinen, J. Tuukkanen, K. Seppänen, J. P. A. Arokoski, P. A. Brama, J. S. Jurvelin, and H. J. Helminen. Physical exercise improves properties of bone and its collagen network in growing and maturing mice. Calcif. Tissue Int. 85(3):247–256, 2009.

    Article  CAS  PubMed  Google Scholar 

  21. Kodama, Y., Y. Umemura, S. Nagasawa, W. G. Beamer, L. R. Donahue, C. R. Rosen, D. J. Baylink, and J. R. Farley. Exercise and mechanical loading increase periosteal bone formation and whole bone strength in C57BL/6J mice but not in C3H/Hej mice. Calcif. Tissue Int. 66:298–306, 2000.

    Article  CAS  PubMed  Google Scholar 

  22. Kohn, D. H., N. D. Sahar, J. M. Wallace, K. Golcuk, and M. D. Morris. Exercise alters mineral and matrix composition in the absence of adding new bone. Cells Tissues Organs 189:33–37, 2009.

    Article  PubMed  Google Scholar 

  23. Kuhn, J. L., S. A. Goldstein, L. A. Feldkamp, R. W. Goulet, and G. Jesion. Evaluation of a microcomputed tomography system to study trabecular bone structure. J. Orthop. Res. 8:833–842, 1990.

    Article  CAS  PubMed  Google Scholar 

  24. Landis, W. J. The strength of a calcified tissue depends in part on the molecular structure and organization of its constituent mineral crystals in their organic matrix. Bone 16:533–544, 1995.

    Article  CAS  PubMed  Google Scholar 

  25. Li, X., W. Gu, G. Masinde, M. Hamilton-Ulland, C. H. Rundle, S. Mohan, and D. J. Baylink. Genetic variation in bone-regenerative capacity among inbred strains of mice. Bone 29:134–140, 2001.

    Article  CAS  PubMed  Google Scholar 

  26. Marusic, A., V. Katavic, D. Grcevic, and I. K. Lukic. Genetic variability of new bone induction in mice. Bone 25:25–32, 1999.

    Article  CAS  PubMed  Google Scholar 

  27. Miller, L. M., W. Little, A. Schirmer, F. Sheik, B. Busa, and S. Judex. Accretion of bone quantity and quality in the developing mouse skeleton. J. Bone Miner. Res. 22:1037–1045, 2007.

    Article  PubMed  Google Scholar 

  28. Mosekilde, L., J. S. Thomsen, P. B. Orhii, R. J. McCarter, W. Mejia, and D. N. Kalu. Additive effect of voluntary exercise and growth hormone treatment on bone strength assessed at four different skeletal sites in an aged rat model. Bone 24:71–80, 1999.

    Article  CAS  PubMed  Google Scholar 

  29. Paschalis, E. P., K. Verdelis, S. B. Doty, A. L. Boskey, R. Mendelsohn, and M. Yamauchi. Spectroscopic characterization of collagen cross-links in bone. J. Bone Miner. Res. 16:1821–1828, 2001.

    Article  CAS  PubMed  Google Scholar 

  30. Robling, A. G., F. M. Hinant, D. B. Burr, and C. H. Turner. Shorter, more frequent mechanical loading sessions enhance bone mass. Med. Sci. Sports Exerc. 34:196–202, 2002.

    Article  PubMed  Google Scholar 

  31. Takagi, M., T. Yamada, N. Kamiya, T. Kumagai, and A. Yamaguchi. Effects of bone morphogenetic protein-2 and transforming growth factor-beta1 on gene expression of decorin and biglycan by cultured osteoblastic cells. Histochem. J. 31:403–409, 1999.

    Article  CAS  PubMed  Google Scholar 

  32. Teti, A., and A. Zallone. Do osteocytes contribute to bone mineral homeostasis? Osteocytic osteolysis revisited. Bone 44:11–16, 2009.

    Article  CAS  PubMed  Google Scholar 

  33. Timlin, J. A., A. Carden, M. D. Morris, R. M. Rajachar, and D. H. Kohn. Raman spectroscopic imaging markers for fatigue-related microdamage in bovine bone. Anal. Chem. 72:2229–2236, 2000.

    Article  CAS  PubMed  Google Scholar 

  34. Turner, C. H., and D. B. Burr. Basic biomechanical measurements of bone: a tutorial. Bone 14:595–607, 1993.

    Article  CAS  PubMed  Google Scholar 

  35. Vaidya, S., C. Karunakaran, B. Pande, N. Gupta, R. Iyer, and S. Karweer. Pressure-induced crystalline to amorphous transition in hydroxylapatite. J. Mater. Sci. 32:3213–3217, 1997.

    Article  CAS  Google Scholar 

  36. Wallace, J. M., K. Golcuk, M. D. Morris, and D. H. Kohn. Inbred strain-specific response to biglycan deficiency in the cortical bone of C57BL6/129 and C3H/He mice. J. Bone Miner. Res. 24:1002–1012, 2009.

    Article  PubMed  Google Scholar 

  37. Wallace, J. M., R. M. Rajachar, M. R. Allen, S. A. Bloomfield, P. G. Robey, M. F. Young, and D. H. Kohn. Exercise-induced changes in the cortical bone of growing mice are bone- and gender-specific. Bone 40:1120–1127, 2007.

    Article  PubMed  Google Scholar 

  38. Wallace, J. M., R. M. Rajachar, X. D. Chen, S. Shi, M. R. Allen, S. A. Bloomfield, C. M. Les, P. G. Robey, M. F. Young, and D. H. Kohn. The mechanical phenotype of biglycan-deficient mice is bone- and gender-specific. Bone 39:106–116, 2006.

    Article  CAS  PubMed  Google Scholar 

  39. Wallace, J. M., M. S. Ron, and D. H. Kohn. Short-term exercise in mice increases tibial post-yield mechanical properties while two weeks of latency following exercise increases tissue-level strength. Calcif. Tissue Int. 84:297–304, 2009.

    Article  CAS  PubMed  Google Scholar 

  40. Wang, X., X. Li, R. A. Bank, and C. M. Agrawal. Effects of collagen unwinding and cleavage on the mechanical integrity of the collagen network in bone. Calcif. Tissue Int. 71:186–192, 2002.

    Article  CAS  PubMed  Google Scholar 

  41. Wang, X., X. Shen, X. Li, and C. M. Agrawal. Age-related changes in the collagen network and toughness of bone. Bone 31:1–7, 2002.

    Article  PubMed  Google Scholar 

  42. Weiner, S., and W. Traub. Bone structure: from angstroms to microns. FASEB J. 6:879–885, 1992.

    CAS  PubMed  Google Scholar 

  43. Wilson, E. E., A. Awonusi, M. D. Morris, D. H. Kohn, M. M. Tecklenburg, and L. W. Beck. Three structural roles for water in bone observed by solid-state NMR. Biophys. J. 90:3722–3731, 2006.

    Article  CAS  PubMed  Google Scholar 

  44. Wilson, E. E., A. Awonusi, M. D. Morris, D. H. Kohn, M. M. Tecklenburg, and L. W. Beck. Highly ordered interstitial water observed in bone by nuclear magnetic resonance. J. Bone Miner. Res. 20:625–634, 2005.

    Article  CAS  PubMed  Google Scholar 

  45. Wolff, J., P. Maquet, and R. Furlong. The Law of Bone Remodelling. Berlin, New York: Springer-Verlag Berlin and Heidelberg GmbH & Co. K, p. 126, 1986.

    Google Scholar 

  46. Xu, T., P. Bianco, L. W. Fisher, G. Longenecker, E. Smith, S. Goldstein, J. Bonadio, A. Boskey, A. M. Heegaard, B. Sommer, K. Satomura, P. Dominguez, C. Zhao, A. B. Kulkarni, P. G. Robey, and M. F. Young. Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice. Nat. Genet. 20:78–82, 1998.

    Article  CAS  PubMed  Google Scholar 

  47. Yeh, J. K., J. F. Aloia, and S. Yasumura. Effect of physical activity on calcium and phosphorus metabolism in the rat. Am. J. Physiol. 256:E1–E6, 1989.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Funding Sources: DoD/US Army DAMD17-03-1-0556; NIH R01 AR050210; NIH P30-AR46024; NIH IPA Agreement; NIH Regenerative Sciences Training Grant R90-DK071506.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, The University of Michigan, Ann Arbor, MI, USA

    Joseph M. Wallace & David H. Kohn

  2. Department of Chemistry, The University of Michigan, Ann Arbor, MI, USA

    Kurtulus Golcuk & Michael D. Morris

  3. Department of Biologic and Materials Sciences, The University of Michigan, 1011 N. University Ave., Ann Arbor, MI, 48109-1078, USA

    David H. Kohn

Authors
  1. Joseph M. Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kurtulus Golcuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael D. Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David H. Kohn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David H. Kohn.

Additional information

Associate Editor Eric M. Darling oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wallace, J.M., Golcuk, K., Morris, M.D. et al. Inbred Strain-Specific Effects of Exercise in Wild Type and Biglycan Deficient Mice. Ann Biomed Eng 38, 1607–1617 (2010). https://doi.org/10.1007/s10439-009-9881-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-009-9881-0

Keywords

Search

Navigation