Nash Anthony, Notou Maria, Lopez-Clavijo Andrea F, Bozec Laurent, de Leeuw Nora H, Birch Helen L
University College London, Institute of Orthopaedics and Musculoskeletal Science, Stanmore Campus, Royal National Orthopaedic Hospital, Stanmore HA7 4LP, UK.
Matrix Biol Plus. 2019 Aug 31;4:100013. doi: 10.1016/j.mbplus.2019.100013. eCollection 2019 Nov.
Collagen glycation, and in particular the formation of advanced glycation end-product (AGE) crosslinks, plays a central role in the ageing process and in many of the long-term complications of diabetes. Glucosepane, the most abundant and relevant AGE crosslink, has been suggested to increase the stiffness of tissue and reduce its solubility, although no evidence is available concerning the mechanisms. We have used a combination of computational and experimental techniques to study a collagen-rich tissue with a relatively simple organisation to further our understanding of the impact of glucosepane on the structural and physical properties of collagen fibrils. Our work shows that glucosepane levels increase dramatically in aged tendon tissue and are associated with the reduced density of collagen packing and increased porosity to water molecules. Our studies provide the basis to understand many of the tissue dysfunctions associated with ageing and diabetes across a range of different tissues types.
胶原蛋白糖基化，尤其是晚期糖基化终产物（AGE）交联的形成，在衰老过程以及糖尿病的许多长期并发症中起着核心作用。葡萄糖基赖氨酸，最丰富且相关的AGE交联物，已被认为会增加组织的硬度并降低其溶解性，尽管尚无关于其机制的证据。我们结合了计算和实验技术，研究组织构成相对简单且富含胶原蛋白的组织，以进一步了解葡萄糖基赖氨酸对胶原纤维结构和物理性质的影响。我们的研究表明，老年肌腱组织中葡萄糖基赖氨酸水平显著升高，且与胶原蛋白堆积密度降低和水分子孔隙率增加有关。我们的研究为理解一系列不同组织类型中与衰老和糖尿病相关的许多组织功能障碍提供了基础。
