Decorin敲除通过增强粘弹性特性的恢复来改善老化肌腱的愈合,而Biglycan可能不会。

IF 3 2区 医学 Q3 ENGINEERING, BIOMEDICAL Annals of Biomedical Engineering Pub Date : 2024-11-29 DOI:10.1007/s10439-024-03612-y
Christelle Darrieutort-Laffite, Stephanie N Weiss, Courtney A Nuss, Joseph B Newton, Jeremy D Eekhoff, Louis J Soslowsky
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引用次数: 0

摘要

本研究的目的是确定decorin和biglycan在老年小鼠肌腱愈合的早期和晚期的具体作用。年龄(300日龄)雌性野生型(WT)、Dcnflox/flox (I-Dcn-/-)、Bgnflox/flox (I-Bgn-/-)和复合Dcnflox/flox/Bgnflox/flox (I-Dcn-/-/Bgn-/-)小鼠用他莫昔芬(TM)诱导的Cre进行双侧髌骨肌腱损伤(PT)。在伤后5天(3周和6周采集样本)或21天(6周采集样本)诱导条件等位基因的Cre切除。瘢痕组织面积、胶原结构、基因表达和力学性能在损伤后重建肌腱结构时进行评估。与WT相比,在第3周和第6周时,纤维直径分布受到decorin和biglycan敲除的影响。尽管I-Bgn-/-肌腱的早期愈合似乎被延迟(3周时瘢痕组织面积更大),但在失败特性方面没有发现差异。到6周时,在I-Dcn-/-肌腱中,我们观察到与WT肌腱相比,当早期诱导敲低时,粘弹性性能恢复得更好(应力松弛减少,动态模量增加)。这可以解释为其他基质蛋白的表达增加,如弹性蛋白,其基因表达在3周时在I-Dcn-/-肌腱中增加。尽管对胶原纤维形成有影响,但decorin和/或biglycan敲低对髌腱损伤后的准静态特性没有可检测到的影响。然而,早期的decorin敲除可以更好地恢复粘弹性。这一结果背后的机制有待进一步的研究来阐明。
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Decorin Knockdown Improves Aged Tendon Healing by Enhancing Recovery of Viscoelastic Properties, While Biglycan May Not.

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), Dcnflox/flox (I-Dcn-/-), Bgnflox/flox (I-Bgn-/-), and compound Dcnflox/flox/Bgnflox/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.

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来源期刊
Annals of Biomedical Engineering
Annals of Biomedical Engineering 工程技术-工程:生物医学
CiteScore
7.50
自引率
15.80%
发文量
212
审稿时长
3 months
期刊介绍: Annals of Biomedical Engineering is an official journal of the Biomedical Engineering Society, publishing original articles in the major fields of bioengineering and biomedical engineering. The Annals is an interdisciplinary and international journal with the aim to highlight integrated approaches to the solutions of biological and biomedical problems.
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