The degenerative impact of hyperglycemia on the structure and mechanics of developing murine intervertebral discs.
The degenerative impact of hyperglycemia on the structure and mechanics of developing murine intervertebral discs.
复制标题
DOI：
10.1002/jsp2.1191
复制
发表时间：
2022-03
期刊：
影响因子：
3.7
通讯作者：
Bonassar LJ
中科院分区：
文献类型：
--
作者：
Lintz M;Walk RE;Tang SY;Bonassar LJ
长期以来，糖尿病一直被认为是椎间盘（IVD）退变的主要风险因素，干扰分子信号传导和基质生物化学，最终导致疾病进展。葡萄糖含量先前已显示影响体外工程椎间盘的结构和组成变化，阻碍纤维形成和机械稳定性。在本研究中，我们通过评估从3至4个月大db/db小鼠尾椎采集的椎间盘的生化成分、胶原纤维结构和机械行为，研究了糖尿病高血糖对年轻IVD的影响。我们发现，从血糖水平升高的糖尿病小鼠中取出的椎间盘显示总糖胺聚糖和胶原蛋白含量增加，但晚期糖基化终产物（AGE）水平与野生型椎间盘相当。糖尿病椎间盘还包含髓核和纤维环之间的边界不清，后者在同一边界处显示出无序和未对齐的胶原纤维网络。这些组成和结构变化对功能产生了不利影响，因为糖尿病椎间盘的硬度是野生型椎间盘的两倍，并且表现出显著的抗变形性。这些结果表明，糖尿病可能倾向于年轻的椎间盘DDD在以后的生活中，通过改变模式的细胞外基质沉积，纤维形成，运动节段力学独立的AGE积累。在这项研究中，我们通过评估从3至4个月大的db/db小鼠尾椎采集的椎间盘的生化成分、胶原纤维结构和力学行为，研究了糖尿病高血糖对年轻椎间盘的影响。这些动物中的晚期糖基化终产物（AGE）蓄积与野生型相当，但在组成、结构和力学方面存在显著差异。这些结果表明，糖尿病可能倾向于年轻的椎间盘DDD在以后的生活中，通过改变模式的细胞外基质沉积，纤维形成，运动节段力学独立的AGE积累。
Diabetes has long been implicated as a major risk factor for intervertebral disc (IVD) degeneration, interfering with molecular signaling and matrix biochemistry, which ultimately aggravates the progression of the disease. Glucose content has been previously shown to influence structural and compositional changes in engineered discs in vitro, impeding fiber formation and mechanical stability. In this study, we investigated the impact of diabetic hyperglycemia on young IVDs by assessing biochemical composition, collagen fiber architecture, and mechanical behavior of discs harvested from 3‐ to 4‐month‐old db/db mouse caudal spines. We found that discs taken from diabetic mice with elevated blood glucose levels demonstrated an increase in total glycosaminoglycan and collagen content, but comparable advanced glycation end products (AGE) levels to wild‐type discs. Diabetic discs also contained ill‐defined boundaries between the nucleus pulposus and annulus fibrosus, with the latter showing a disorganized and unaligned collagen fiber network at this same boundary. These compositional and structural changes had a detrimental effect on function, as the diabetic discs were twice as stiff as their wild‐type counterparts and demonstrated a significant resistance to deformation. These results indicate that diabetes may predispose the young disc to DDD later in life by altering patterns of extracellular matrix deposition, fiber formation, and motion segment mechanics independently of AGE accumulation. In this study, we investigated the impact of diabetic hyperglycemia on young intervertebral discs by assessing biochemical composition, collagen fiber architecture, and mechanical behavior of discs harvested from 3‐ to 4‐month‐old db/db mouse caudal spines. Advanced glycation end products (AGE) accumulation in these animals was comparable to their wild‐type counterparts, but there were significant differences in composition, structure, and mechanics. These results indicate that diabetes may predispose the young disc to DDD later in life by altering patterns of extracellular matrix deposition, fiber formation, and motion segment mechanics independently of AGE accumulation.
登录
查看更多内容
影响因子：
2.8
作者：
Fields, Aaron J.;Berg-Johansen, Britta;Metz, Lionel N.;Miller, Stephanie;La, Brandan;Liebenberg, Ellen C.;Coughlin, Dezba G.;Graham, James L.;Stanhope, Kimber L.;Havel, Peter J.;Lotz, Jeffrey C.
通讯作者：
Lotz, Jeffrey C.
影响因子：
2.9
作者：
Bowles, Robby D.;Gebhard, Harry H.;Bonassar, Lawrence J.
通讯作者：
Bonassar, Lawrence J.
影响因子：
3
作者：
BUCKWALTER, JA
通讯作者：
BUCKWALTER, JA
影响因子：
4.1
作者：
Bowles, Robby D.;Williams, Rebecca M.;Bonassar, Lawrence J.
通讯作者：
Bonassar, Lawrence J.
DOI：
10.1073/pnas.1107094108
发表时间：
2011-08-09
影响因子：
11.1
作者：
Bowles, Robby D.;Gebhard, Harry H.;Bonassar, Lawrence J.
通讯作者：
Bonassar, Lawrence J.