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. 2013 Jan;32(1):3-13.
doi: 10.1016/j.matbio.2012.11.005. Epub 2012 Nov 23.

Decorin expression is important for age-related changes in tendon structure and mechanical properties

Andrew A Dunkman  1 , Mark R Buckley, Michael J Mienaltowski, Sheila M Adams, Stephen J Thomas, Lauren Satchell, Akash Kumar, Lydia Pathmanathan, David P Beason, Renato V Iozzo, David E Birk, Louis J Soslowsky
Affiliations

Decorin expression is important for age-related changes in tendon structure and mechanical properties

Andrew A Dunkman et al. Matrix Biol. 2013 Jan.

Abstract

The aging population is at an increased risk of tendon injury and tendinopathy. Elucidating the molecular basis of tendon aging is crucial to understanding the age-related changes in structure and function in this vulnerable tissue. In this study, the structural and functional features of tendon aging are investigated. In addition, the roles of decorin and biglycan in the aging process were analyzed using transgenic mice at both mature and aged time points. Our hypothesis is that the increase in tendon injuries in the aging population is the result of altered structural properties that reduce the biomechanical function of the tendon and consequently increase susceptibility to injury. Decorin and biglycan are important regulators of tendon structure and therefore, we further hypothesized that decreased function in aged tendons is partly the result of altered decorin and biglycan expression. Biomechanical analyses of mature (day 150) and aged (day 570) patellar tendons revealed deteriorating viscoelastic properties with age. Histology and polarized light microscopy demonstrated decreased cellularity, alterations in tenocyte shape, and reduced collagen fiber alignment in the aged tendons. Ultrastructural analysis of fibril diameter distributions indicated an altered distribution in aged tendons with an increase of large diameter fibrils. Aged wild type tendons maintained expression of decorin which was associated with the structural and functional changes seen in aged tendons. Aged patellar tendons exhibited altered and generally inferior properties across multiple assays. However, decorin-null tendons exhibited significantly decreased effects of aging compared to the other genotypes. The amelioration of the functional deficits seen in the absence of decorin in aged tendons was associated with altered tendon fibril structure. Fibril diameter distributions in the decorin-null aged tendons were comparable to those observed in the mature wild type tendon with the absence of the subpopulation containing large diameter fibrils. Collectively, our findings provide evidence for age-dependent alterations in tendon architecture and functional activity, and further show that lack of stromal decorin attenuates these changes.

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Figures

Fig. 1
Fig. 1
Dynamic mechanical properties of mature and aged patellar tendons. [A] The dynamic modulus (∣E*∣: the ratio of stress to strain measured in oscillatory applied displacement) at 6% strain for WT tendons at 150 and 570 days old. Aged tendons exhibited significantly decreased dynamic modulus revealing greater deformability at all frequencies. [B] Dynamic modulus at 1 Hz, shown at 4%, 6% and 8% strains. Results were consistent across all strains and frequencies (see Table 1, Supplemental Data S1). [C] Tangent of phase angle δ at 6% for WT tendons (δ: the angular gap between peaks of stress and strain sinusoids; tanδ: equal to ratio of dissipated force to stored force). Aged tendons had significantly higher phase angles demonstrating increased viscoelasticity and force dissipation. [D] Phase angle at 1 Hz, shown for 4%, 6% and 8% stains. Significance bars denote p≤0.05.
Fig. 2
Fig. 2
Quasi-static mechanical properties of mature and aged patellar tendons across genotypes. [A] A decrease in linear modulus was detected for WT only (p=0.04), revealing that WT tendons become more easily deformable with age. [B] WT and Bgn−/− had significant increases with age in transition strain, which is indicative that with age, these genotypes’ tendon properties are changing in ways not observed in Dcn−/−. [C] No significant differences were observed for transition stress. [D] No significant differences by age were observed for toe modulus for any genotype. Significance bars denote p≤0.05.
Fig. 3
Fig. 3
Comparisons of morphological features of tendons across age and genotype. WT tendons exhibited significant decreased cellularity (number of cells) with age [G] and significantly elongated (more spindle like) cell shape [H]. Mean with interquartile range. Significance bars denote p≤0.05. Note: Grading performed on original images [Supplemental Data S9]. For publication, filters applied to images [A–F]: auto-tone, auto-contrast, and auto-color (all three to each individually). Contrast decreased and brightness increased (to all at once). Cropped.
Fig. 4
Fig. 4
Collagen fiber alignment by age and genotype. Mean with standard deviation. Circular standard deviation is a measure of un-alignment. Lower values reflect more aligned fibrils. [A] WT tendon collagen is significantly less aligned with age. [B] There are no significant differences in alignment across genotypes in mature tendons. [C] Dcn−/− at day 570 is significantly more aligned than WT at day 570—which may explain the reduced decrease in mechanical properties with age. Significance bars denote p≤0.05.
Fig. 5
Fig. 5
Collagen fibril diameter measurements by age and genotype. Transmission electronmicroscopymeasured distribution of fibril diameters at P150 and P570 for [A]WT, [B] Bgn−/− and [C] Dcn−/−. With aging, WT undergoes a shift to a bimodal distribution with an increase in larger fibrils. Bgn−/− converges toward a single mean. Dcn−/− experiences the least change with age.
Fig. 6
Fig. 6
RT-qPCR for SLRP expression. Biglycan [A] and decorin [B] are effectively suppressed in respective knockouts. The apparent increase in decorin expression with age for WT did not reach statistical significance. [C] Fibromodulin is evidently neither up- nor down-regulated by either genotype or age. [D] Lumican expression is significantly greater in the Bgn−/− genotype at P570. Significance bars denote p ≤0.05; dashed bars denote p≤0.1.
Fig. 7
Fig. 7
Percentage change relationships of biomechanical data suggest decorin expression is a major factor in tendon aging. [A] Within-genotype percentage change with age for dynamic modulus at 6% strain. The percentage change for Dcn−/− is significantly smaller than it is for WT. This means that the increase in deformability (decrease in modulus) that is associated with age, is much less pronounced for Dcn−/− tendons. [B] Within-genotype percentage change with age for dynamic modulus at 1 Hz. The percentage decline is smaller for Dcn−/− than for wild type or Bgn−/− [C] Within-genotype percentage change with age for tangent of phase angle at 6% strain. The percentage change for Dcn−/− is significantly smaller than it is for WT or Bgn−/−. Thus, the increase in viscosity associated with age is less pronounced in the Dcn−/− tendons. [D] Within-genotype percentage change with age for tangent of phase angle at 1 Hz. Dcn−/− shows the least percentage change. Significance bars denote p≤0.05; dashed bars denote p≤0.1. See SD 4 for 4% and 8% strains; Table 1 for complete statistics.
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