非酶促糖化可减少人体软骨终板中的葡萄糖运输,与基质孔隙率或蛋白多糖含量无关

IF 3.4 3区 医学 Q1 ORTHOPEDICS JOR Spine Pub Date : 2023-10-24 DOI:10.1002/jsp2.1297
Jae-Young Jung, Mohamed Habib, Luke J. Morrissette, Shannon C. Timmons, Tristan Maerz, Aaron J. Fields
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引用次数: 0

摘要

背景椎间盘退化与腰背痛有关,而腰背痛是导致残疾的主要原因。虽然椎间盘退化的确切原因尚不清楚,但通过软骨终板(CEP)的营养和代谢物运输不足可能是一个重要因素。之前的研究表明,CEP的运输特性取决于CEP基质的孔隙率,但对于CEP特性的作用却知之甚少,而这些特性可能会独立于孔隙率影响运输特性。在这里,我们发现 CEP 的运输特性取决于 CEP 基质的非酶糖化程度。 方法和结果 通过体外核糖基化诱导非酶糖化并促进高级糖化终产物的形成,我们发现与未发生核糖基化的供体和部位匹配的 CEP 组织相比,核糖基化使人体尸体腰部 CEP 组织的葡萄糖分配系数平均降低了 10.7%(p = 0.04)。在 CEP 孔隙度(p = 0.89)或硫酸化糖胺聚糖(sGAGs,p = 0.47)或胶原蛋白(p = 0.61)含量没有差异的情况下,也能观察到葡萄糖摄取量的减少。为了研究核糖基化是否会改变 sGAG 分子上的固定电荷与移动游离离子之间的静电相互作用,我们利用微计算机断层扫描技术,通过阳离子造影剂的平衡分配来测量 CEP 基质中的电荷密度。对比增强后,经过核糖基化的 CEP 组织的平均 X 射线衰减降低了 11.9%(p = 0.02),这意味着 CEP 基质的负电荷较少。 结论 综上所述,这些研究结果表明,非酶糖化会对 CEP 中的葡萄糖转运产生负面影响,与基质孔隙率或 sGAG 含量无关,而且这种影响可能是由基质电荷密度的改变介导的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Non-enzymatic glycation reduces glucose transport in the human cartilage endplate independently of matrix porosity or proteoglycan content

Background

Intervertebral disc degeneration is associated with low back pain, which is a leading cause of disability. While the precise causes of disc degeneration are unknown, inadequate nutrient and metabolite transport through the cartilage endplate (CEP) may be one important factor. Prior work shows that CEP transport properties depend on the porosity of the CEP matrix, but little is known about the role of CEP characteristics that could influence transport properties independently from porosity. Here, we show that CEP transport properties depend on the extent of non-enzymatic glycation of the CEP matrix.

Methods and Results

Using in vitro ribosylation to induce non-enzymatic glycation and promote the formation of advanced glycation end products, we found that ribosylation reduced glucose partition coefficients in human cadaveric lumbar CEP tissues by 10.7%, on average, compared with donor- and site-matched CEP tissues that did not undergo ribosylation (p = 0.04). These reductions in glucose uptake were observed in the absence of differences in CEP porosity (p = 0.89) or in the amounts of sulfated glycosaminoglycans (sGAGs, p = 0.47) or collagen (p = 0.61). To investigate whether ribosylation altered electrostatic interactions between fixed charges on the sGAG molecules and the mobile free ions, we measured the charge density in the CEP matrix using equilibrium partitioning of a cationic contrast agent using micro-computed tomography. After contrast enhancement, mean X-ray attenuation was 11.9% lower in the CEP tissues that had undergone ribosylation (p = 0.02), implying the CEP matrix was less negatively charged.

Conclusions

Taken together, these findings indicate that non-enzymatic glycation negatively impacts glucose transport in the CEP independent of matrix porosity or sGAG content and that the effects may be mediated by alterations to matrix charge density.

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来源期刊
JOR Spine
JOR Spine ORTHOPEDICS-
CiteScore
6.40
自引率
18.90%
发文量
42
审稿时长
10 weeks
期刊最新文献
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