Relationships between decorin and biglycan, structure and tendon mechanics using mutant mouse models.

摘要

Tendons have a complex mechanical behavior that depends on their composition and structure. Understanding structure-function relationships may elucidate important differences in the functional behaviors of specific tendons and guide targeted treatment modalities and tissue engineered constructs. Specifically, the interactions of small leucine-rich proteoglycans (SLRPs) with collagen fibrils, association with water and role in fibrillogenesis suggest that SLRPs may play an important role in tendon mechanics. Some studies have assessed the role of SLRPs in the mechanical response of tendon, but the relationships between sophisticated mechanics, assembly of collagen and SLRPs have not been well characterized. Therefore, the aim of this study was to evaluate the structure-function relationships between complex tendon mechanics, structure and composition with a focus on decorin and biglycan, two Class I SLRPs. Utilizing homozygous null and heterozygous mutant genotype mouse models, the amount of SLRPs were varied to allow for the study of the "dose" response on tendon mechanics. A statistical model was used to explore the coordinated roles of the measured matrix molecules to better understand the structure-function relationships in tendon and account for compensation often seen in mutant models. In the decorin and biglycan mutant genotype mice, no changes were seen in any elastic tensile or compressive properties compared to wild type. However, viscoelastic mechanical properties were altered in decorin heterozygotes and biglycan nulls and heterozygotes. Compensatory increases in the expression of other SLRPs were noted in the biglycan mutant genotypes. Changes were also found in total collagen content and collagen structure, although collagen characteristics could not completely explain the viscoelastic changes measured. These results suggest that decorin and biglycan play a role in tendon viscoelasticity. Finally, a multiple regression statistical model was used to determine the compositional and structural components that predict mechanical properties. Challenges with this type of model with small tissue size were discussed. Complex interactions between SLRPs and collagen were present in all models and demonstrate the importance of considering the amounts of other components in the tissue when examining structure-function relationships.