Collagen XI regulates the acquisition of collagen fibril structure, organization and functional properties in tendon.

ABSTRACT: Collagen XI is a fibril-forming collagen that regulates collagen fibrillogenesis. Collagen XI is normally associated with collagen II-containing tissues such as cartilage, but it also is expressed broadly during development in collagen I-containing tissues, including tendons. The goals of this study are to define the roles of collagen XI in regulation of tendon fibrillar structure and the relationship to function. A conditional Col11a1-null mouse model was created to permit the spatial and temporal manipulation of Col11a1 expression. We hypothesize that collagen XI functions to regulate fibril assembly, organization and, therefore, tendon function. Previous work using cho mice with ablated Col11a1 alleles supported roles for collagen XI in tendon fibril assembly. Homozygous cho/cho mice have a perinatal lethal phenotype that limited the studies. To circumvent this, a conditional Col11a1^flox/flox mouse model was created where exon 3 was flanked with loxP sites. Breeding with Scleraxis-Cre (Scx-Cre) mice yielded a tendon-specific Col11a1-null mouse line, Col11a1^?ten/?ten. Col11a1^flox/flox mice had no phenotype compared to wild type C57BL/6 mice and other control mice, e.g., Col11a1^flox/flox and Scx-Cre. Col11a1^flox/flox mice expressed Col11a1 mRNA at levels comparable to wild type and Scx-Cre mice. In contrast, in Col11a1^?ten/?ten mice, Col11a1 mRNA expression decreased to baseline in flexor digitorum longus tendons (FDL). Collagen XI protein expression was absent in Col11a1^?ten/?ten FDLs, and at ~50% in Col11a1^+/?ten compared to controls. Phenotypically, Col11a1^?ten/?ten mice had significantly decreased body weights (p?-/- mice indicated that the primary regulatory foci for collagen XI was in development. In mature Col11a1^?ten/?ten FDLs a significant decrease in the biomechanical properties was observed. The decrease in maximum stress and modulus suggest that fundamental differences in the material properties in the absence of Col11a1 expression underlie the mechanical deficiencies. These data demonstrate an essential role for collagen XI in regulation of tendon fibril assembly and organization occurring primarily during development.

SUBMITTER: Sun M 

PROVIDER: S-EPMC7722227 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature