0
Research Papers

Effect of Age and Proteoglycan Deficiency on Collagen Fiber Re-Alignment and Mechanical Properties in Mouse Supraspinatus Tendon

[+] Author and Article Information
Joseph J. Sarver, Louis J. Soslowsky

McKay Orthopaedic Research Laboratory,
University of Pennsylvania,
424 Stemmler Hall,
36th and Hamilton Walk,
Philadelphia, PA 19104

Renato V. Iozzo

Professor
Pathology & Cell Biology,
Biochemistry & Molecular Biology,
Kimmel Cancer Center,
Department of Pathology,
Anatomy & Cell Biology,
Thomas Jefferson University,
1020 Locust Street Suite 336 JAH,
Philadelphia, PA 19107

David E. Birk

Department of Molecular Pharmacology and Physiology,
University of South Florida,
Morsani College of Medicine,
Tampa, FL 33612

1Corresponding author.

Contributed by the Bioengineering Division of ASME for publication in the Journal of Biomechanical Engineering. Manuscript received September 25, 2012; final manuscript received December 5, 2012; accepted manuscript posted December 22, 2012; published online February 7, 2013. Editor: Victor H. Barocas.

J Biomech Eng 135(2), 021019 (Feb 07, 2013) (8 pages) Paper No: BIO-12-1434; doi: 10.1115/1.4023234 History: Received September 25, 2012; Revised December 05, 2012

Collagen fiber realignment is one mechanism by which tendon responds to load. Re-alignment is altered when the structure of tendon is altered, such as in the natural process of aging or with alterations of matrix proteins, such as proteoglycan expression. While changes in re-alignment and mechanical properties have been investigated recently during development, they have not been studied in (1) aged tendons, or (2) in the absence of key proteoglycans. Collagen fiber re-alignment and the corresponding mechanical properties are quantified throughout tensile mechanical testing in both the insertion site and the midsubstance of mouse supraspinatus tendons in wild type (WT), decorin-null (Dcn-/-), and biglycan-null (Bgn-/-) mice at three different ages (90 days, 300 days, and 570 days). Percent relaxation was significantly decreased with age in the WT and Dcn-/- tendons, but not in the Bgn-/- tendons. Changes with age were found in the linear modulus at the insertion site where the 300 day group was greater than the 90 day and 570 day group in the Bgn-/- tendons and the 90 day group was smaller than the 300 day and 570 day groups in the Dcn-/- tendons. However, no changes in modulus were found across age in WT tendons were found. The midsubstance fibers of the WT and Bgn-/- tendons were initially less aligned with increasing age. The re-alignment was significantly altered with age in the WT tendons, with older groups responding to load later in the mechanical test. This was also seen in the Dcn-/- midsubstance and the Bgn-/- insertion, but not in the other locations. Although some studies have found changes in the WT mechanical properties with age, this study did not support those findings. However, it did show fiber re-alignment changes at both locations with age, suggesting a breakdown of tendon's ability to respond to load in later ages. In the proteoglycan-null tendons however, there were changes in the mechanical properties, accompanied only by location-dependent re-alignment changes, suggesting a site-specific role for these molecules in loading. Finally, changes in the mechanical properties did not occur in concert with changes in re-alignment, suggesting that typical mechanical property measurements alone are insufficient to describe how structural alterations affect tendon's response to load.

FIGURES IN THIS ARTICLE
<>
Copyright © 2013 by ASME
Your Session has timed out. Please sign back in to continue.

References

Vogel, H. G., 1978, “Influence of Maturation and Age on Mechanical and Biochemical Parameters of Connective Tissue of Various Organs in the Rat,” Connect. Tissue Res., 6(3), pp. 161–166. [CrossRef] [PubMed]
Nielsen, H. M., Skalicky, M., and Viidik, A., 1998, “Influence of Physical Exercise on Aging Rats. III. Life-Long Exercise Modifies the Aging Changes of the Mechanical Properties of Limb Muscle Tendons,” Mech. Ageing Dev., 100(3), pp. 243–260. [CrossRef] [PubMed]
Shadwick, R. E., 1990, “Elastic Energy Storage in Tendons: Mechanical Differences Related to Function and Age,” J. Appl. Physiol., 68(3), pp. 1033–1040. [CrossRef] [PubMed]
Haut, R. C., Lancaster, R. L., and Decamp, C. E., 1992, “Mechanical Properties of the Canine Patellar Tendon: Some Correlations With Age and the Content of Collagen,” J. Biomech., 25(2), pp. 163–173. [CrossRef] [PubMed]
Dressler, M. R., Butler, D. L., Wenstrup, R., Awad, H. A., Smith, F., and Boivin, G. P., 2002, “A Potential Mechanism for Age-Related Declines in Patellar Tendon Biomechanics,” J. Orthop. Res., 20(6), pp. 1315–1322. [CrossRef] [PubMed]
Buckwalter, J. A., Heckman, J. D., and Petrie, D. P., 2003, “An AOA Critical Issue: Aging of the North American Population: New Challenges for Orthopaedics,” J. Bone Joint Surg. Am., 85-A(4), pp. 748–758. [PubMed]
Scott, J. E., 1992, “Supramolecular Organization of Extracellular Matrix Glycosaminoglycans, In Vitro and in the Tissues,” FASEB J., 6(9), pp. 2639–2645. [PubMed]
Redaelli, A., Vesentini, S., Soncini, M., Vena, P., Mantero, S., and Montevecchi, F. M., 2003, “Possible Role of Decorin Glycosaminoglycans in Fibril to Fibril Force Transfer in Relative Mature Tendons—A Computational Study From Molecular to Microstructural Level,” J. Biomech., 36(10), pp. 1555–1569. [CrossRef] [PubMed]
Kishore, V., Paderi, J. E., Akkus, A., Smith, K. M., Balachandran, D., Beaudoin, S., Panitch, A., and Akkus, O., 2011, “Incorporation of a Decorin Biomimetic Enhances the Mechanical Properties of Electrochemically Aligned Collagen Threads,” Acta Biomater., 7(6), pp. 2428–2436. [CrossRef] [PubMed]
Fessel, G., and Snedeker, J. G., 2009, “Evidence Against Proteoglycan Mediated Collagen Fibril Load Transmission and Dynamic Viscoelasticity in Tendon,” Matrix Biol., 28(8), pp. 503–510. [CrossRef] [PubMed]
Lujan, T. J., Underwood, C. J., Henninger, H. B., Thompson, B. M., and Weiss, J. A., 2007, “Effect of Dermatan Sulfate Glycosaminoglycans on the Quasi-Static Material Properties of the Human Medial Collateral Ligament,” J. Orthop. Res., 25(7), pp. 894–903. [CrossRef] [PubMed]
Screen, H. R., Shelton, J. C., Chhaya, V. H., Kayser, M. V., Bader, D. L., and Lee, D. A., 2005, “The Influence of Noncollagenous Matrix Components on the Micromechanical Environment of Tendon Fascicles,” Ann. Biomed. Eng., 33(8), pp. 1090–1099. [CrossRef] [PubMed]
Dourte, L. M., Pathmanathan, L., Jawad, A. F., Iozzo, R. V., Mienaltowski, M. J., Birk, D. E., and Soslowsky, L. J., 2012, “Influence of Decorin on the Mechanical, Compositional, and Structural Properties of the Mouse Patellar Tendon,” ASME J. Biomech. Eng., 134(3), p. 031005. [CrossRef]
Ansorge, H., Adams, S., Birk, D., and Soslowsky, L., 2011, “Mechanical, Compositional, and Structural Properties of the Post-Natal Mouse Achilles Tendon,” Ann. Biomed. Eng., 39(7), pp. 1904–1913. [CrossRef] [PubMed]
Buckley, M. R., Pathmanathan, L., Mienaltowski, M. J., Dunkman, A. A., Kumar, A., Beason, D. P., Iozzo, R. V., Birk, D. E., and Soslowsky, L. J., 2012, “Age-Related Changes in Tendon Mechanical Properties are not Enhanced by the Absence of Biglycan and Decorin,” Trans. Orthop. Res. Soc., 37, p. 1308.
Miller, K., Connizzo, B., and Soslowsky, L., 2012, “Collagen Fiber Re-Alignment in a Neonatal Developmental Mouse Supraspinatus Tendon Model,” Ann. Biomed. Eng., 40(5), pp. 1102–1110. [CrossRef] [PubMed]
Miller, K. S., Connizzo, B. K., Feeney, E., and Soslowsky, L. J., 2012, “Characterizing Local Collagen Fiber Re-Alignment and Crimp Behavior Throughout Mechanical Testing in a Mature Mouse Supraspinatus Tendon Model,” J. Biomech., 45(12), pp. 2061–2065. [CrossRef] [PubMed]
Favata, M., 2006, “Scarless Healing in the Fetus: Implications and Strategies for Postnatal Tendon Repair,” Ph.D. thesis, University of Pennsylvania, Philadelphia.
Lake, S. P., Miller, K. S., Elliott, D. M., and Soslowsky, L. J., 2009, “Effect of Fiber Distribution and Realignment on the Nonlinear and Inhomogeneous Mechanical Properties of Human Supraspinatus Tendon Under Longitudinal Tensile Loading,” J. Orthop. Res., 27(12), pp. 1596–1602. [CrossRef] [PubMed]
Derwin, K. A., Soslowsky, L. J., Green, W. D., and Elder, S. H., 1994, “A New Optical System for the Determination of Deformations and Strains: Calibration Characteristics and Experimental Results,” J. Biomech., 27(10), pp. 1277–1285. [CrossRef] [PubMed]
Peltz, C. D., Sarver, J. J., Dourte, L. M., Wurgler-Hauri, C. C., Williams, G. R., and Soslowsky, L. J., 2010, “Exercise Following a Short Immobilization Period is Detrimental to Tendon Properties and Joint Mechanics in a Rat Rotator Cuff Injury Model,” J. Orthop. Res., 28(7), pp. 841–845. [CrossRef] [PubMed]
See supplementary material at for additional figures presenting total population re-alignment data and failure stress.
Vogel, H. G., 1983, “Age Dependence of Mechanical Properties of Rat Tail Tendons (Hysteresis Experiments),” Aktuelle Gerontol., 13(1), pp. 22–27. [PubMed]
Willett, T. L., Labow, R. S., Aldous, I. G., Avery, N. C., and Lee, J. M., 2010, “Changes in Collagen With Aging Maintain Molecular Stability After Overload: Evidence From an In Vitro Tendon Model,” ASME J. Biomech. Eng., 132(3), p. 031002. [CrossRef]
Zhang, G., Ezura, Y., Chervoneva, I., Robinson, P. S., Beason, D. P., Carine, E. T., Soslowsky, L. J., Iozzo, R. V., and Birk, D. E., 2006, “Decorin Regulates Assembly of Collagen Fibrils and Acquisition of Biomechanical Properties During Tendon Development,” J. Cell. Biochem., 98(6), pp. 1436–1449. [CrossRef] [PubMed]
Robinson, P. S., Huang, T.-f., Kazam, E., Iozzo, R. V., Birk, D. E., and Soslowsky, L. J., 2005, “Influence of Decorin and Biglycan on Mechanical Properties of Multiple Tendons in Knockout Mice,” ASME J. Biomech. Eng., 127(1), pp. 181–185. [CrossRef]
Watanabe, T., Imamura, Y., Suzuki, D., Hosaka, Y., Ueda, H., Hiramatsu, K., and Takehana, K., 2012, “Concerted and Adaptive Alignment of Decorin Dermatan Sulfate Filaments in the Graded Organization of Collagen Fibrils in the Equine Superficial Digital Flexor Tendon,” J. Anat., 220(2), pp. 156–163. [CrossRef] [PubMed]
Eckert, C. E., Fan, R., Mikulis, B., Barron, M., Carruthers, C. A., Friebe, V. M., Vyavahare, N. R., and Sacks, M. S., 2012, “On the Biomechanical Role of Glycosaminoglycans in the Aortic Heart Valve Leaflet,” Acta Biomat., 9(1), pp. 4653–4660.
Birk, D. E., Southern, J. F., Zycband, E. I., Fallon, J. T., and Trelstad, R. L., 1989, “Collagen Fibril Bundles: A Branching Assembly Unit in Tendon Morphogenesis,” Development, 107(3), pp. 437–443. [PubMed]

Figures

Grahic Jump Location
Fig. 1

(a) Image of tendon showing stain lines for regional analysis, (b) testing setup of Instron integrated with polarized light system, and (c) mechanical testing protocol. Images were taken for alignment analysis at: (1) before preconditioning, (2) after preconditioning, (3) after the initial displacement of the stress relaxation (SR), (4) after a return to zero displacement, (5) at the transition strain, and (6) at a point in the linear-region. (Not to scale)

Grahic Jump Location
Fig. 2

Mechanical changes are present across age and across genotype in the (a) cross-sectional area, (b) percent relaxation, (c) transition strain at the insertion site, and (d) transition stress at the midsubstance

Grahic Jump Location
Fig. 3

(a) Significant changes with age were found in the linear modulus at the insertion site with the Bgn-/- and Dcn-/- tendons. (b) No changes in the midsubstance linear modulus were found.

Grahic Jump Location
Fig. 4

The initial circular variance of collagen fibers in the midsubstance of the tendon increased with age in the WT and Bgn-/- tendons, denoting a less aligned tendon with age (larger distribution of fiber angles)

Grahic Jump Location
Fig. 5

Re-alignment of wild type (WT) tendons at later ages shows a progressively later response of tendons to the application of load in both the insertion site and the midsubstance. Data is presented as a representative sample for each group with population statistics noted. Each line connects the alignment at one point of the mechanical test to the alignment at the next point, i.e., the ‘B’ segment connects the ‘before preconditioning (no. 1 in Fig. 1)’ point to the ‘after preconditioning (no. 2 in Fig. 1)’ point. This segment therefore represents the change in alignment, or the re-alignment, occurring during the preconditioning segment of the mechanical test. A significant change in re-alignment is represented as a line segmented in bold with a significance star (*p <0.025).

Grahic Jump Location
Fig. 6

Re-alignment of decorin-null (Dcn-/-) tendons at later ages shows a progressively later response of the tendons to the application of load at the midsubstance but not at the insertion site. Data is presented as representative samples with population statistics for nonparametric data.

Grahic Jump Location
Fig. 7

Re-alignment of biglycan-null (Bgn-/-) tendons at later ages shows a progressively later response of the tendons to the application of load in the insertion but not in the midsubstance. Data is presented as representative samples with population statistics for nonparametric data.

Tables

Errata

Discussions

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In