Pleiotropic roles of the matricellular protein Sparc in tendon maturation and ageing.
Pleiotropic roles of the matricellular protein Sparc in tendon maturation and ageing.
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DOI：
10.1038/srep32635
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发表时间：
2016-09-02
影响因子：
4.6
通讯作者：
Traweger A
中科院分区：
文献类型：
--
作者：
Gehwolf R;Wagner A;Lehner C;Bradshaw AD;Scharler C;Niestrawska JA;Holzapfel GA;Bauer HC;Tempfer H;Traweger A
急性和慢性肌腱病在临床上仍然具有挑战性，肌腱容易随着年龄的增长而退化或损伤。尽管肌腱疾病在老年人中的患病率很高，但我们目前对肌腱功能随年龄而变差的机制的了解仍然非常有限。在这里，我们表明，分泌的蛋白质酸性和富含半胱氨酸（Sparc）的表达显着降低健康老年小鼠跟腱。Sparc的缺失导致肌腱胶原纤维形成缺陷，并且Sparc−/−肌腱与其各自的野生型对应物相比承受力较低。在细胞水平上，Sparc无效和健康老年肌腱衍生细胞表现出更收缩的表型和改变肌动蛋白细胞骨架。此外，观察到成脂标记基因PPARγ和Cebpα的表达升高，同时老年和Sparc−/−肌腱中脂质沉积增加。总之，我们认为肌腱中的Sparc水平对于适当的胶原原纤维成熟及其年龄相关性降低至关重要，同时ECM特性的变化有利于肌腱中的脂质增生。
Acute and chronic tendinopathies remain clinically challenging and tendons are predisposed to degeneration or injury with age. Despite the high prevalence of tendon disease in the elderly, our current understanding of the mechanisms underlying the age-dependent deterioration of tendon function remains very limited. Here, we show that Secreted protein acidic and rich in cysteine (Sparc) expression significantly decreases in healthy-aged mouse Achilles tendons. Loss of Sparc results in tendon collagen fibrillogenesis defects and Sparc−/− tendons are less able to withstand force in comparison with their respective wild type counterparts. On the cellular level, Sparc-null and healthy-aged tendon-derived cells exhibited a more contracted phenotype and an altered actin cytoskeleton. Additionally, an elevated expression of the adipogenic marker genes PPARγ and Cebpα with a concomitant increase in lipid deposits in aged and Sparc−/− tendons was observed. In summary, we propose that Sparc levels in tendons are critical for proper collagen fibril maturation and its age-related decrease, together with a change in ECM properties favors lipid accretion in tendons.
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影响因子：
7.8
作者：
Kohler J;Popov C;Klotz B;Alberton P;Prall WC;Haasters F;Müller-Deubert S;Ebert R;Klein-Hitpass L;Jakob F;Schieker M;Docheva D
通讯作者：
Docheva D
影响因子：
7.7
作者：
Kalson NS;Lu Y;Taylor SH;Starborg T;Holmes DF;Kadler KE
通讯作者：
Kadler KE
影响因子：
11.4
作者：
Gilmour, DT;Lyon, GJ;Colledge, WH
通讯作者：
Colledge, WH
影响因子：
82.9
作者：
Bi, Yanming;Ehirchiou, Driss;Young, Marian F.
通讯作者：
Young, Marian F.
DOI：
10.1115/1.2898732
发表时间：
2008-04-01
影响因子：
1.7
作者：
Goh, K. L.;Holmes, D. F.;Wess, T. J.
通讯作者：
Wess, T. J.