Nanoscale changes in collagen are reflected in physical and mechanical properties of bone at the microscale in diabetic rats.

Nanoscale changes in collagen are reflected in physical and mechanical properties of bone at the microscale in diabetic rats.
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DOI:
10.1016/j.bone.2013.11.015
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发表时间:
2014-03
期刊:
影响因子:
4.1
通讯作者:
Wallace, Joseph M.
Wallace, Joseph M.
中科院分区:
医学2区
文献类型:
--
作者:
Hammond, Max A.;Gallant, Maxime A.;Burr, David B.;Wallace, Joseph M.

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糖尿病会因晚期糖基化终末产物 (AGE) 增加而使胶原蛋白基质变硬,从而对肌肉骨骼系统产生不利影响。在这项研究中,使用原子力显微镜将 Zucker 糖尿病 Sprague-Dawley (ZDSD) 大鼠的胫骨和肌腱与 Sprague-Dawley 衍生对照 (CD) 大鼠进行比较。使用拉曼光谱和参考点压痕 (RPI) 比较 ZDSD 和 CD 胫骨。 ZDSD 骨的胶原蛋白 D 间距分布与 CD 显着不同(p = 0.015;ZDSD n = 294 根原纤维;CD n = 274 根原纤维),其变化更大并转向更高的值。 ZDSD 和 CD D 间距分布之间的这种转变在肌腱中更为明显(p < 0.001;ZDSD n = 350;CD n = 371)。拉曼显示,尽管骨矿物质密度 (aBMD) 和灰分分数较低,表明糖尿病可能会优先降低胶原蛋白的拉曼特征,但 ZDSD 中骨基质矿化测量值显着增加(PO43− ν1/Amide I p = 0.008;PO43− ν1/CH2 wag p = 0.047;每组 n = 5)。在 ZDSD 大鼠中通过 RPI(每组 n = 9 只)测量的压痕距离增加(p = 0.010)和蠕变压痕距离(p = 0.040)减少,表明在与 RPI 相关的高应力下,基质在该长度范围内更能抵抗压痕。 ZDSD 群体(n = 18 个位置)的拉曼和 RPI 测量值之间存在显着相关性,但 CD 群体(n = 16 个位置)则不然,这表明虽然 RPI 相对不受生物噪声的影响,但它对疾病引起的成分变化很敏感。总之,ZDSD 大鼠的糖尿病会导致胶原蛋白纳米级形态的变化,从而导致骨骼在微观尺度上产生成分和机械效应。
Diabetes detrimentally affects the musculoskeletal system by stiffening the collagen matrix due to increased advanced glycation end products (AGEs). In this study, tibiae and tendon from Zucker diabetic Sprague-Dawley (ZDSD) rats were compared to Sprague-Dawley derived controls (CD) using Atomic Force Microscopy. ZDSD and CD tibiae were compared using Raman Spectroscopy and Reference Point Indentation (RPI). ZDSD bone had a significantly different distribution of collagen D-spacing than CD (p = 0.015; ZDSD n = 294 fibrils; CD n = 274 fibrils) which was more variable and shifted to higher values. This shift between ZDSD and CD D-spacing distribution was more pronounced in tendon (p < 0.001; ZDSD n = 350; CD n = 371). Raman revealed significant increases in measures of bone matrix mineralization in ZDSD (PO43− ν1/Amide I p = 0.008; PO43− ν1/CH2 wag p = 0.047; n = 5 per group) despite lower bone mineral density (aBMD) and ash fraction indicating diabetes may preferentially reduce the Raman signature of collagen. Decreased indentation distance increase (p = 0.010) and creep indentation distance (p = 0.040) measured by RPI (n = 9 per group) in ZDSD rats suggest a matrix more resistant to indentation under the high stresses associated with RPI at this length scale. There were significant correlations between Raman and RPI measurements in the ZDSD population (n = 18 locations) but not the CD population (n = 16 locations) indicating that while RPI is relatively unaffected by biological noise, it is sensitive to disease-induced compositional changes. In conclusion, diabetes in the ZDSD rat causes changes to the nanoscale morphology of collagen that result in compositional and mechanical effects in bone at the microscale.
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