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

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.

Tendon development and musculoskeletal assembly: emerging roles for the extracellular matrix

“…This fibrillar organization is essential for tendons to bear the stress of muscle contraction and prevent bone detachment (avulsion fractures) by controlling force distribution Pan et al, 2013;Schwartz et al, 2013;Pingel et al, 2014). The fibrillar network of proteins includes: (1) Dunkman et al, 2013). Although the integration of structural collagens into fibrils has been well documented, recent studies have provided insight into the functions of scaffolding proteins and specialized collagens during fibril assembly.…”

“…These are found in relatively small amounts in tendons, yet loss-of-function mutations in the genes encoding these proteins disrupt collagen fibrillogenesis (Chakravarti, 2002;Corsi et al, 2002;Zhang et al, 2006). SLRPs mainly crosslink collagen fibrils, but they also appear to cross-regulate one another's transcription through as yet unknown mechanisms (Yoon and Halper, 2005;Zhang et al, 2006;Dunkman et al, 2013). This might involve feedback regulation of Scx and Mkx expression through the tendon ECM, and recent studies have suggested that Dcn and Fmod are regulated by Mkx (Fig.…”

Collagen V-heterozygous and -null supraspinatus tendons exhibit altered dynamic mechanical behaviour at multiple hierarchical scales

“…Twenty specimens from each group designated for dynamic viscoelastic testing were subjected to a testing protocol as described previously [13,14,40]. Tendons were first preloaded and preconditioned for 10 cycles to 1.5% grip strain at 0.25 Hz.…”

“…In addition, the dynamic modulus jE*j (defined as the stress amplitude divided by the strain amplitude) and the phase angle d (between the stress and strain) were computed at each frequency and strain level. The dynamic modulus (jE*j) represents how difficult the material is to deform under dynamic loading, while the tangent of the phase angle (tan d) is the ratio of loss over storage moduli [13,14,40,42]. Comparisons were made using one-way ANOVA for each parameter with post-hoc Bonferroni tests to correct for family-wise error associated with multiple comparisons.…”

Role of Metalloproteinases in Tendon Pathophysiology

“…The major proteoglycan present in the proximal/tensional regions of the tendon is decorin [16][17][18], even though lower amounts of other proteoglycans, such as biglycan, aggrecan and versican, have also been detected [19,20]. Decorin and biglycan belong to the small leucine-rich family of proteoglycans (characterized by leucine-rich repeat structures) which have been proposed to be directly involved in the binding of proteoglycans to collagen [21].…”