AGE-RELATED DETERIORATION OF BONE TOUGHNESS IS RELATED TO DIMINISHING AMOUNT OF MATRIX GLYCOSAMINOGLYCANS (GAGS).
AGE-RELATED DETERIORATION OF BONE TOUGHNESS IS RELATED TO DIMINISHING AMOUNT OF MATRIX GLYCOSAMINOGLYCANS (GAGS).
复制标题
与年龄相关的骨韧性退化与基质糖胺聚糖 (GAGS) 量的减少有关。
作者：
Wang,Xiaodu;Hua,Rui;Ahsan,Abu;Ni,Qingwen;Huang,Yehong;Gu,Sumin;Jiang,JeanX
水化状态显著影响骨的韧性。除了胶原相之外，最近的证据表明，细胞外基质中蛋白聚糖（PG）的糖胺聚糖（GAGs）也在调节骨骼组织水平水合状态方面发挥着关键作用，从而影响骨骼组织水平的韧性。在这项研究中，我们假设骨基质中GAG的量随着年龄的增长而减少，这种变化将导致结合水的减少，随后导致骨组织水平韧性的降低。为了检验假设，进行纳米划痕试验以测量人尸体骨样本的组织水平韧性，所述样本仅从三个不同年龄组的男性供体获得：年轻（年龄26 ± 6岁）、中年（年龄52 ± 5岁）和老年（年龄73 ± 5岁），每组6名供体。通过生物化学和组织化学方法测定骨基质中糖胺聚糖和蛋白多糖的含量和主要亚型。此外，低场核磁共振（NMR）测量，以确定骨基质中的结合水含量。结果表明，老化导致骨基质中GAG的统计学显著减少（17%）。同时，随着年龄的增长，观察到骨组织水平韧性显著恶化（20%）。最重要的是，骨组织水平韧性的恶化与年龄相关的结合水减少（40%）显著相关，这部分是由骨基质中GAG的减少引起的。此外，我们确定硫酸软骨素（CS）是一种主要的GAGs亚型，CS的量随着年龄的增长而减少，同时伴有骨中PGs的主要亚型双糖链的减少。本研究的结果表明，骨基质中GAG的减少可能是与年龄相关的骨质量恶化的分子起源之一。© 2017 The Authors.JBMR Plus由Wiley Periodicals，Inc.出版。美国骨骼和矿物质研究协会的代表。
Hydration status significantly affects the toughness of bone. In addition to the collagen phase, recent evidence shows that glycosaminoglycans (GAGs) of proteoglycans (PGs) in the extracellular matrix also play a pivotal role in regulating the tissue level hydration status of bone, thereby affecting the tissue level toughness of bone. In this study, we hypothesized that the amount of GAGs in bone matrix decreased with age and such changes would lead to reduction in bound water and subsequently result in a decrease in the tissue level toughness of bone. To test the hypothesis, nanoscratch tests were conducted to measure the tissue level toughness of human cadaveric bone specimens, which were procured only from male donors in three different age groups: young (aged 26 ± 6 years), mid aged (aged 52 ± 5 years), and elderly (aged 73 ± 5 years), with 6 donors in each group. Biochemical and histochemical assays were performed to determine the amount and major subtypes of GAGs and proteoglycans in bone matrix. In addition, low field nuclear magnetic resonance (NMR) measurements were implemented to determine bound water content in bone matrix. The results demonstrated that aging resulted in a statistically significant reduction (17%) of GAGs in bone matrix. Concurrently, a significant deterioration (20%) of tissue level toughness of bone with age was observed. Most importantly, the deteriorated tissue level toughness of bone was associated significantly with the age related reduction (40%) of bound water, which was partially induced by the decrease of GAGs in bone matrix. Furthermore, we identified that chondroitin sulfate (CS) was a major subtype of GAGs, and the amount of CS decreased with aging accompanied with a decrease of biglycan that is a major subtype of PGs in bone. The findings of this study suggest that reduction of GAGs in bone matrix is likely one of the molecular origins for age related deterioration of bone quality. © 2017 The Authors.JBMR Plusis published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.