Darrieutort-Laffite Christelle, Weiss Stephanie N, Nuss Courtney A, Newton Joseph B, Eekhoff Jeremy D, Soslowsky Louis J
McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Regenerative Medicine and Skeleton, RMeS, UMR 1229, Nantes Université, CHU Nantes, INSERM, F-44000, Nantes, France.
Ann Biomed Eng. 2025 Mar;53(3):622-633. doi: 10.1007/s10439-024-03612-y. Epub 2024 Nov 29.
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 (I-Dcn), Bgn (I-Bgn), and compound Dcn/Bgn (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.
本研究的目的是确定核心蛋白聚糖和双糖链蛋白聚糖在老年小鼠肌腱愈合早期和晚期的具体作用。对300日龄的老年雌性野生型(WT)、Dcn(I-Dcn)、Bgn(I-Bgn)和复合Dcn/Bgn(I-Dcn/Bgn)小鼠(带有他莫昔芬(TM)诱导型Cre)进行双侧髌腱损伤(PT)。在损伤后5天(在3周和6周收集样本)或21天诱导条件等位基因的Cre切除(在6周收集样本)。在损伤后肌腱结构重建过程中评估瘢痕组织面积、胶原结构、基因表达和力学性能。与野生型相比,在3周和6周时,核心蛋白聚糖和双糖链蛋白聚糖敲低均影响原纤维直径分布。尽管I-Bgn肌腱的早期愈合似乎延迟(3周时瘢痕组织面积更大),但未检测到破坏特性的差异。到6周时,在I-Dcn肌腱中,当早期诱导敲低时,与野生型肌腱相比,我们观察到粘弹性性能有更好的恢复(应力松弛降低,动态模量增加)。这可以通过其他基质蛋白表达的增加来解释,例如在I-Dcn肌腱中3周时弹性蛋白基因表达增加。尽管对胶原纤维形成有影响,但核心蛋白聚糖和/或双糖链蛋白聚糖敲低在髌腱损伤后对准静态特性未产生可检测到的影响。然而,早期核心蛋白聚糖敲低导致粘弹性性能有更好的恢复。该结果的潜在机制有待进一步研究阐明。