Decorin expression is important for age-related changes in tendon structure and mechanical properties.

Decorin expression is important for age-related changes in tendon structure and mechanical properties.
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DOI:
10.1016/j.matbio.2012.11.005
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发表时间:
2013-01
期刊:
影响因子:
6.9
通讯作者:
Soslowsky, Louis J.
Soslowsky, Louis J.
中科院分区:
生物学1区
文献类型:
--
作者:
Dunkman, Andrew A.;Buckley, Mark R.;Mienaltowski, Michael J.;Adams, Sheila M.;Thomas, Stephen J.;Satchell, Lauren;Kumar, Akash;Pathmanathan, Lydia;Beason, David P.;Iozzo, Renato V.;Birk, David E.;Soslowsky, Louis J.

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老龄化人群患肌腱损伤和肌腱病的风险增加。阐明肌腱老化的分子基础对于理解这一脆弱组织中与年龄相关的结构和功能变化至关重要。在这项研究中,肌腱老化的结构和功能特征进行了调查。此外,使用转基因小鼠在成熟和老化时间点分析核心蛋白聚糖和双糖链蛋白聚糖在衰老过程中的作用。我们的假设是,在老龄化人群中肌腱损伤的增加是由于改变的结构特性,降低了肌腱的生物力学功能,从而增加了对损伤的敏感性。核心蛋白聚糖和双糖链蛋白聚糖是肌腱结构的重要调节因子,因此,我们进一步假设老年肌腱功能下降部分是核心蛋白聚糖和双糖链蛋白聚糖表达改变的结果。成熟(150天)和老年(570天)髌腱的生物力学分析显示,随着年龄的增长,粘弹性性能恶化。组织学和偏振光显微镜显示,减少细胞,肌腱细胞形状的改变,并减少胶原纤维排列在老年肌腱。原纤维直径分布的超微结构分析表明,改变分布在老年肌腱大直径原纤维的增加。老年野生型肌腱保持核心蛋白聚糖的表达,这与老年肌腱中观察到的结构和功能变化有关。在多项试验中,老化髌腱表现出改变且通常较差的特性。然而,与其他基因型相比,核心蛋白聚糖缺失的肌腱表现出显着降低的衰老效应。在缺乏核心蛋白聚糖的情况下,老年肌腱功能缺陷的改善与肌腱原纤维结构的改变有关。原纤维直径分布在核心蛋白聚糖无效的老年肌腱中观察到的那些在成熟的野生型肌腱的情况下,含有大直径原纤维的亚群。总的来说,我们的研究结果为肌腱结构和功能活动的年龄依赖性改变提供了证据,并进一步表明缺乏基质核心蛋白聚糖减弱了这些变化。
The aging population is at an increased risk of tendon injury and tendinopathy. Elucidating the molecular basis of tendon aging is crucial to understanding the age-related changes in structure and function in this vulnerable tissue. In this study, the structural and functional features of tendon aging are investigated. In addition, the roles of decorin and biglycan in the aging process were analyzed using transgenic mice at both mature and aged time points. Our hypothesis is that the increase in tendon injuries in the aging population is the result of altered structural properties that reduce the biomechanical function of the tendon and consequently increase susceptibility to injury. Decorin and biglycan are important regulators of tendon structure and therefore, we further hypothesized that decreased function in aged tendons is partly the result of altered decorin and biglycan expression. Biomechanical analyses of mature (day 150) and aged (day 570) patellar tendons revealed deteriorating viscoelastic properties with age. Histology and polarized light microscopy demonstrated decreased cellularity, alterations in tenocyte shape, and reduced collagen fiber alignment in the aged tendons. Ultrastructural analysis of fibril diameter distributions indicated an altered distribution in aged tendons with an increase of large diameter fibrils. Aged wild type tendons maintained expression of decorin which was associated with the structural and functional changes seen in aged tendons. Aged patellar tendons exhibited altered and generally inferior properties across multiple assays. However, decorin-null tendons exhibited significantly decreased effects of aging compared to the other genotypes. The amelioration of the functional deficits seen in the absence of decorin in aged tendons was associated with altered tendon fibril structure. Fibril diameter distributions in the decorin-null aged tendons were comparable to those observed in the mature wild type tendon with the absence of the subpopulation containing large diameter fibrils. Collectively, our findings provide evidence for age-dependent alterations in tendon architecture and functional activity, and further show that lack of stromal decorin attenuates these changes.
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