Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands; Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, Delft 2628 CD, The Netherlands.
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
J Mech Behav Biomed Mater. 2018 Jan;77:551-556. doi: 10.1016/j.jmbbm.2017.09.035. Epub 2017 Sep 30.
The mechanical properties of articular cartilage depend on the quality of its matrix, which consists of collagens and glycosaminoglycans (GAGs). The accumulation of advanced glycation end products (AGEs) can greatly affect the mechanics of cartilage. In the current study, we simulated the accumulation of AGEs by using L-threose to cross-link collagen molecules in the cartilage matrix (in vitro). The resulting changes in the mechanical properties (stiffness) of cartilage are then measured both at the micrometer-scale (using micro-indenter) and nanometer-scale (using indentation-type atomic force microscopy). Non-enzymatic cross-linking within the cartilage matrix was confirmed by the browning of L-threose-treated samples. We observed > 3 times increase in the micro-scale stiffness and up to 12-fold increase in the nano-scale stiffness of the glycated cartilage in the peak pertaining to the collagen fibers, which is caused by cartilage network embrittlement. At the molecular level, we found that besides the collagen component, the glycation process also influenced the GAG macromolecules. Comparing cartilage samples before and after L-threose treatment revealed that artificially induced-AGEs also decelerate in vitro degradation (likely via matrix metalloproteinases), observed at both micro- and nano-scales. The combined observations suggest that non-enzymatic glycation may play multiple roles in mechanochemical functioning of articular cartilage.
关节软骨的力学性能取决于其基质的质量，基质由胶原蛋白和糖胺聚糖（GAGs）组成。晚期糖基化终产物（AGEs）的积累会极大地影响软骨的力学性能。在目前的研究中，我们使用 L-苏糖在软骨基质中交联胶原蛋白分子来模拟 AGEs 的积累（体外）。然后，我们使用微压痕仪（在微米尺度上）和压痕原子力显微镜（在纳米尺度上）测量软骨力学性能（硬度）的变化。通过 L-苏糖处理样本的褐变证实了软骨基质内的非酶交联。我们观察到，在胶原纤维峰处，糖化软骨的微尺度硬度增加了 3 倍以上，纳米尺度硬度增加了 12 倍，这是由于软骨网络变脆所致。在分子水平上，我们发现除了胶原蛋白成分外，糖化过程还影响 GAG 大分子。比较 L-苏糖处理前后的软骨样本表明，人工诱导的 AGEs 也会减缓体外降解（可能通过基质金属蛋白酶），在微米和纳米尺度上均有观察。综合观察表明，非酶糖化可能在关节软骨的机械化学功能中发挥多种作用。
