Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development

Abstract

Tendon function involves the development of an organized hierarchy of collagen fibrils. Small leucine-rich proteoglycans have been implicated in the regulation of fibrillogenesis and decorin is the prototypic member of this family. Decorin-deficient mice demonstrate altered fibril structure and mechanical function in mature skin and tail tendons. However, the developmental role(s) of decorin needs to be elucidated. To define these role(s) during tendon development, tendons (flexor digitorum longus) were analyzed ultrastructurally from postnatal day 10 to 90. Decorin-deficient tendons developed abnormal, irregularly contoured fibrils. Finite mixture modeling estimated that the mature tendon was a three-subpopulation mixture of fibrils with characteristic diameter ranges. During development, in each subpopulation the mean diameter was consistently larger in mutant mice. Also, diameter distributions and the percentage of fibrils in each subpopulation were altered. Biomechanical analyses demonstrated that mature decorin-deficient tendons had significantly reduced strength and stiffness; however, there was no reduction in immature tendons. Expression of decorin and biglycan, a closely related family member, was analyzed during development. Decorin increased with development while biglycan decreased. Spatially, both had a comparable localization throughout the tendon. Biglycan expression increased substantially in decorin-deficient tendons suggesting a potential functional compensation. The accumulation of structural defects during fibril growth, a period associated with decorin expression and low biglycan expression, may be the cause of compromised mechanical function in the absence of decorin. Our findings indicate that decorin is a key regulatory molecule and that the temporal switch from biglycan to decorin is an important event in the coordinate regulation of fibrillogenesis and tendon development.

Influence of cyclic strain and decorin deficiency on 3D cellularized collagen matrices

“…Thus, it was believed that absence of decorin would lead to weaker tissues and that the opposite trend could be expected if decorin is overexpressed. However, either superior or similar material parameters have recently been reported for tendons from decorin deficient adult [37] and postnatal mice [34] as well as decorin deficient engineered gels [16], compared to wild-type controls. In addition, greater than normal decorin expression has been reported in prolapsed mitral valve [38] in which the tissue is weakened [39], and our lab has histochemically demonstrated that excess decorin is present valves that were exposed to altered shear stress [40].…”

“…Even though decorin and biglycan are often found in different regions of the extracellular matrix and respond differently to growth factors [4], biglycan competes with decorin for the same binding site on type I collagen fibrils [4]. Thus, compensatory behavior of biglycan has been reported in Dcn −/− cell-seeded collagen gels and native tissues [16,34,35].…”

Modulation of aggrecan and ADAMTS expression in ovine tendinopathy induced by altered strain

“…Together, the PG changes in this overstrained tensile tendon may negatively impact the structural integrity and mechanical properties of the tendon and potentially predispose to rupture. Reduced levels of small leucine-rich PGs would be expected to affect collagen fibrillogenesis and fibril mechanical properties as well as increase the susceptibility of the collagen fibers to cleavage by collagenolytic MMPs (47)(48)(49).…”

Mechanisms of cartilage growth: Modulation of balance between proteoglycan and collagen in vitro using chondroitinase ABC

“…Although the nature of such interactions in normal cartilage is not well established, collagen-binding molecules (such as type IX collagen and decorin) can regulate collagen fibril length and diameter during development (41,42) and may also mediate the adherence and sliding between collagen fibrils and act as functional noncovalent linkages within the extracellular matrix (43,44). While aggrecan contains most of the chondroitinase ABC-susceptible material of the tissue, depletion of GAG with chondroitinase ABC may alter or displace some of these other chondroitin sulfate-or dermatan sulfate-containing molecules and allow new interactions between collagen fibrils that enhance the tensile integrity of the collagen network.…”