Decorin Knockdown Improves Aged Tendon Healing by Enhancing Recovery of Viscoelastic Properties, While Biglycan May Not.

Abstract

The objective of the study was to determine the specific roles of decorin and biglycan in the early and late phases of tendon healing in aged mice. Aged (300 day-old) female wildtype (WT), Dcn^flox/flox (I-Dcn^-/-), Bgn^flox/flox (I-Bgn^-/-), and compound Dcn^flox/flox/Bgn^flox/flox (I-Dcn^-/-/Bgn^-/-) mice with a tamoxifen (TM) inducible Cre underwent a bilateral patellar tendon injury (PT). Cre excision of the conditional alleles was induced at 5 days (samples collected at 3 and 6 weeks) or 21 days post-injury (samples collected at 6 weeks). Scar tissue area, collagen architecture, gene expression and mechanical properties were assessed during re-establishment of tendon architecture after injury. Fibril diameter distribution was impacted by both decorin and biglycan knockdown at 3 and 6 weeks compared to WT. Although early healing appeared to be delayed in the I-Bgn^-/- tendons (larger scar tissue area at 3 weeks), no differences in failure properties were detected. By 6 weeks, in the I-Dcn^-/- tendons, we observed a better recovery of viscoelastic properties compared to the WT tendons (reduced stress relaxation and increased dynamic modulus) when the knockdown was induced early. This could be explained by the increased expression of other matrix proteins, such as elastin whose gene expression was increased at 3 weeks in the I-Dcn^-/- tendons. Despite an impact on collagen fibrillogenesis, decorin and/or biglycan knockdown did not produce a detectable effect on quasi-static properties after patellar tendon injury. However, early decorin knockdown resulted in better recovery of viscoelastic properties. Mechanisms underlying this result remained to be clarified in further studies.