Age-related type I collagen modifications reveal tissue-defining differences between ligament and tendon.
Age-related type I collagen modifications reveal tissue-defining differences between ligament and tendon.
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DOI：
10.1016/j.mbplus.2021.100070
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发表时间：
2021-12
影响因子：
--
通讯作者：
Eyre DR
中科院分区：
文献类型：
--
作者：
Hudson DM;Archer M;Rai J;Weis M;Fernandes RJ;Eyre DR
肌腱和韧带胶原蛋白在其翻译后赖氨酸和交联化学方面不同。在韧带胶原蛋白中，羟基赖氨酰醛，永久交联占主导地位。肌腱胶原蛋白具有基于赖氨酰和羟基赖氨酰醛的交联混合物。肌腱的轮廓似乎更适合于促进纤维基质的生长、结构重塑和修复。肌腱和韧带倾向于汇集成一个单一的类别，作为胶原结缔组织的致密弹性带。它们确实有许多相似的特性，例如，两种组织都是将骨骼连接到肌肉或骨骼的纤维组织的柔性索。肌腱和韧带都容易退化和断裂，只有有限的愈合能力，尽管肌腱往往比韧带愈合得更快。I型胶原蛋白构成肌腱和韧带干重的约80%，并且主要负责每个组织的核心强度。胶原蛋白合成是一个复杂的过程，具有多个步骤和许多翻译后修饰，包括脯氨酸和赖氨酸羟基化、羟基赖氨酸糖基化和共价交联。分子内和分子间交联的化学、位置和数量被认为是胶原的材料强度和生物学性质的组织特异性变化的关键因素。随着肌腱和韧带的生长和发育，胶原蛋白交联被称为化学成熟，加强和改变轮廓。因此，交联和其他翻译后修饰的变化可能与组织发育和变性相关。利用质谱，我们比较了胎儿和成年牛膝关节的肌腱和韧带，以研究胶原蛋白翻译后性质的变化。虽然在I型胶原蛋白螺旋交联赖氨酸残基的羟基化水平在所有成人组织中是相似的，韧带有显着更高的糖基化水平在这些网站相比，肌腱。赖氨酸羟基化的差异也被发现在端肽交联位点的组织之间。总胶原交联分析，包括成熟的三价交联和未成熟的二价交联，揭示了肌腱和韧带组织之间独特的交联配置文件。发现肌腱与韧带相比具有显著更高的较小直径胶原纤维的频率，我们怀疑这与每个组织的独特交联特征在功能上相关。了解定义和区分这些特殊组织的特定分子特征对于改善骨科治疗方法的设计非常重要。
Tendon and ligament collagens differ in their post-translational lysine and cross-linking chemistry. In ligament collagen, hydroxylysyl aldehyde, permanent cross-linking dominates. Tendon collagen has a mix of cross-links based on lysyl and hydroxylysyl aldehydes. The profile in tendon appears more adapted to facilitating growth, structural remodeling and repair of the fibrillar matrix. Tendons and ligaments tend to be pooled into a single category as dense elastic bands of collagenous connective tissue. They do have many similar properties, for example both tissues are flexible cords of fibrous tissue that join bone to either muscle or bone. Tendons and ligaments are both prone to degenerate and rupture with only limited capacity to heal, although tendons tend to heal faster than ligaments. Type I collagen constitutes about 80% of the dry weight of tendons and ligaments and is principally responsible for the core strength of each tissue. Collagen synthesis is a complex process with multiple steps and numerous post-translational modifications including proline and lysine hydroxylation, hydroxylysine glycosylation and covalent cross-linking. The chemistry, placement and quantity of intramolecular and intermolecular cross-links are believed to be key contributors to the tissue-specific variations in material strength and biological properties of collagens. As tendons and ligaments grow and develop, the collagen cross-links are known to chemically mature, strengthen and change in profile. Accordingly, changes in cross-linking and other post-translational modifications are likely associated with tissue development and degeneration. Using mass spectrometry, we have compared tendon and ligaments from fetal and adult bovine knee joints to investigate changes in collagen post-translational properties. Although hydroxylation levels at the type I collagen helical cross-linking lysine residues were similar in all adult tissues, ligaments had significantly higher levels of glycosylation at these sites compared to tendon. Differences in lysine hydroxylation were also found between the tissues at the telopeptide cross-linking sites. Total collagen cross-linking analysis, including mature trivalent cross-links and immature divalent cross-links, revealed unique cross-linking profiles between tendon and ligament tissues. Tendons were found to have a significantly higher frequency of smaller diameter collagen fibrils compared with ligament, which we suspect is functionally associated with the unique cross-linking profile of each tissue. Understanding the specific molecular characteristics that define and distinguish these specialized tissues will be important to improving the design of orthopedic treatment approaches.