Proteomic analysis reveals age-related changes in tendon matrix composition, with age- and injury-specific matrix fragmentation.
Proteomic analysis reveals age-related changes in tendon matrix composition, with age- and injury-specific matrix fragmentation.
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DOI：
10.1074/jbc.m114.566554
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发表时间：
2014-09-12
期刊：
影响因子：
--
通讯作者：
Clegg PD
中科院分区：
文献类型：
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作者：
Peffers MJ;Thorpe CT;Collins JA;Eong R;Wei TK;Screen HR;Clegg PD
背景：对肌腱基质成分随老化和损伤的变化知之甚少。结果：衰老和损伤导致不同的蛋白质谱，与年龄特异性肽段的损伤。结论：与老化和损伤相关的蛋白质裂解的鉴定提示老化肌腱的维护和修复受损。意义：发现的新肽段是肌腱损伤和年龄相关性变性的潜在生物标志物。储能肌腱，如人的跟腱和马的浅趾屈肌腱（SDFT），非常容易受伤，其发生率随着年龄的增长而增加。导致老年肌腱损伤增加的细胞和分子机制尚未完全确立，但被认为是导致基质周转改变。然而，很少有人试图充分表征肌腱蛋白质组，也没有确定特定肌腱蛋白质的丰度如何随着衰老和/或损伤而变化。因此，本研究的目的是，使用无标记的相对定量，以确定不同年龄组之间的差异丰富的蛋白质和肽片段，以评估从年轻和年老的马正常SDFT的蛋白质谱。还评估了来自年轻和年老马的损伤SDFT的蛋白质谱。结果表明，不同的蛋白质组分布在年轻和年老的肌腱，与参与基质组织和调节细胞张力的蛋白质水平的改变。此外，我们确定了几个新的肽片段（新肽）存在于老年肌腱，这表明有年龄特异性的切割模式内的SDFT。蛋白质组图谱也不同之间的年轻和老年受伤的肌腱，与更多的新肽确定在年轻受伤的肌腱。这项研究增加了与肌腱老化和损伤相关的分子事件的知识，表明老年人肌腱组织的维护和修复可能会减少，并可能有助于解释为什么损伤的风险随着年龄的增长而增加。
Background: Alterations in tendon matrix composition with aging and injury are poorly understood. Results: Aging and injury resulted in distinct protein profiles, with age-specific peptide fragmentation in injury. Conclusion: Identification of protein cleavages associated with aging and injury suggest impaired maintenance and repair in aged tendon. Significance: Novel peptide fragments identified are potential biomarkers of tendon injury and age-related degeneration. Energy storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT), are highly prone to injury, the incidence of which increases with aging. The cellular and molecular mechanisms that result in increased injury in aged tendons are not well established but are thought to result in altered matrix turnover. However, little attempt has been made to fully characterize the tendon proteome nor determine how the abundance of specific tendon proteins changes with aging and/or injury. The aim of this study was, therefore, to assess the protein profile of normal SDFTs from young and old horses using label-free relative quantification to identify differentially abundant proteins and peptide fragments between age groups. The protein profile of injured SDFTs from young and old horses was also assessed. The results demonstrate distinct proteomic profiles in young and old tendon, with alterations in the levels of proteins involved in matrix organization and regulation of cell tension. Furthermore, we identified several new peptide fragments (neopeptides) present in aged tendons, suggesting that there are age-specific cleavage patterns within the SDFT. Proteomic profile also differed between young and old injured tendon, with a greater number of neopeptides identified in young injured tendon. This study has increased the knowledge of molecular events associated with tendon aging and injury, suggesting that maintenance and repair of tendon tissue may be reduced in aged individuals and may help to explain why the risk of injury increases with aging.