Decorin and/or biglycan knockdown in aged mouse patellar tendon impacts fibril morphology, scar area, and mechanical properties

Abstract

Small leucine-rich proteoglycans, such as decorin and biglycan, play pivotal roles in collagen fibrillogenesis during development, healing, and aging in tendon. Previous work has shown that the absence of decorin and biglycan affects fibril shape and mechanical properties during tendon healing. However, the roles of decorin and biglycan in the healing process of aged tendons are unclear. Therefore the objective of this study was to evaluate the differential roles of decorin and biglycan during healing of patellar tendon injury in aged mice. Aged (300 days old) female Dcn^+/+/Bgn^+/+ control (WT, n = 52), Dcn^flox/flox (I-Dcn^−/−, n = 36), Bgn^flox/flox (I-Bgn^−/−, n = 36), and compound Dcn^flox/flox/Bgn^flox/flox (I-Dcn^−/−/Bgn^−/−, n = 36) mice with a tamoxifen-inducible Cre were utilized. Targeted gene expression, collagen fibril diameter distributions, mechanical properties, and histological assays were employed to assess the effects of knockdown of decorin and/or biglycan at the time of injury. Knockdown resulted in alterations in fibril diameter distribution and scar area, but surprisingly did not lead to many differences in mechanical properties. Biglycan played a larger role in early healing stages, while decorin is more significant in later stages, particularly in scar remodeling. This study highlights some of the differential roles of biglycan and decorin in the regulation of fibril structure and scar area, as well as influencing gene expression during healing in aged mice.