Knockdown of biglycan reveals an important role in maintenance of structural and mechanical properties during tendon aging

Abstract

Biglycan, a small leucine‐rich proteoglycan (SLRP), is involved in collagen fibrillogenesis and also acts as a signaling molecule. Although decorin has been considered as the primary SLRP in developing and maintaining tendon structure and mechanics, more recent work using inducible knockdown models suggests that biglycan is involved in tendon homeostasis. The purpose of the study was to determine the role of biglycan in tendon homeostasis to maintain mechanical and structural integrity in aged mice. Aged (485 days old) female Bgn+/+ control (wild type [WT], n = 16) and 16 bitransgenic conditional Bgnflox/flox mice (I‐Bgn−/−, n = 16) with a tamoxifen‐inducible Cre (driven by ROSA) were utilized. After biglycan knockdown, the transgenic model demonstrated effective knockdown of the target gene without any compensation from other SLRPs or type I collagen. Patellar tendon cellularity was not modified after biglycan knockdown. However, biglycan knockdown had an impact on collagen fibrillogenesis with a higher percentage of small diameter fibrils (25–45 nm) and a lower percentage of medium size fibrils (150–165 nm) in I‐Bgn−/− tendons. Biglycan knockdown also induced a reduction in the midsubstance modulus and maximum stress compared to WT. Stress relaxation was reduced at 4% strain in I‐Bgn−/− tendons but no changes were observed in dynamic modulus and tan delta. As in mature tendons (120 days old), this study showed significant effects of biglycan knockdown on mechanical and structural properties of aged tendons only 30 days after knockdown. These data suggest that biglycan has a major role in maintaining homeostasis in aged tendon.

The alteration of the structure and macroscopic mechanical response of porcine patellar tendon by elastase digestion

“…It is said that insufficient elastin changes the recruitment of collagen fibers, causing tissue elongation, and the straightness of collagen fibers leads to a delay in the ability of tissues to bear loads (Grant et al, 2015;Fazaeli et al, 2020). After elastin degradation, the patellar tendon is in an extended state without a preload, similar to the phenomenon where the joint relaxes (Eekhoff et al, 2023), and the natural tissue becomes more malleable, severely harming the human body. In this study, the low and high moduli after enzyme treatment were significantly reduced, which was similar to a study on bronchus (Mariano et al, 2023).…”

“…The patellar tendons were taken out of the refrigerator at −20 °C and placed in 1χPBS buffer for 30–60 min at room temperature to completely thaw ( Buján et al, 2000 ; Lee and Eliott, 2017 ; Darrieutort-Laffite et al, 2023 ; Solis-Cordova et al, 2023 ). Then they were evenly divided into three parts along the direction from the femur to the tibia (n = 9, proximal, central, and distal; Figure 1A ( Rigozzi et al, 2009 ).…”

“…Clinical research has shown that elastic fibers are affected by hereditary diseases such as Marfan syndrome and skin laxity, causing joint relaxation which damages the mechanical integrity of the tendons and connective tissues near the joints (Zhang et al, 2022;Krarup et al, 2023). Elastic fibers degenerate during aging, possibly causing a loss of anti-fatigue ability and increasing the risk of tendon injury in older adults (Eekhoff et al, 2023). As a dense connective tissue, elastin in the patellar tendon can combine with molecules, such as decorin and dimers, affecting the mechanical properties of the tendon (Beach et al, 2022).…”

“…The elastin content and function of different species and types of tendons are different, and the elastin content of human tendons is the highest, compared with pigs, cows and mice (Eekhoff et al, 2023). Before entering the experimental study of human tendon injury repair, it is generally verified on animal models.…”