Non-enzymatic glycation reduces glucose transport in the human cartilage endplate independently of matrix porosity or proteoglycan content.
Non-enzymatic glycation reduces glucose transport in the human cartilage endplate independently of matrix porosity or proteoglycan content.
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DOI：
10.1002/jsp2.1297
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发表时间：
2024-03
期刊：
影响因子：
3.7
通讯作者：
Fields, Aaron J.
中科院分区：
文献类型：
--
作者：
Jung, Jae-Young;Habib, Mohamed;Morrissette, Luke J.;Timmons, Shannon C.;Maerz, Tristan;Fields, Aaron J.
关键词：
腰椎间盘退变与腰痛有关，这是导致残疾的主要原因。虽然椎间盘退变的确切原因尚不清楚，但营养物质和代谢产物通过软骨终板(CEP)的运输不足可能是一个重要因素。以前的工作表明，CEP的传输特性取决于CEP基质的孔隙率，但对于CEP特性可能独立于孔隙率影响传输特性的作用知之甚少。在这里，我们表明CEP的运输性质依赖于CEP基质的非酶糖基化程度。使用体外核糖化来诱导非酶糖化并促进晚期糖基化终末产物的形成，我们发现核糖化使人身体腰椎癌组织中的葡萄糖分配系数平均降低了10.7%，与未进行核糖化的供体和位点匹配的癌组织相比(p = 0.04)。这些葡萄糖摄取的减少是在没有CEP孔隙率(p = 0.89)或硫酸糖胺多聚糖(sGAGs，p = 0.47)或胶原(p = 0.61)的情况下观察到的。为了研究核糖化是否改变了SGAG分子上固定电荷和可移动自由离子之间的静电相互作用，我们利用微型计算机断层扫描技术，利用阳离子造影剂的平衡分配测量了CEP基质中的电荷密度。对比剂增强后，接受核糖化处理的癌旁组织的平均X射线衰减降低了11.9%(p = 0.02)，这意味着癌旁组织基质的负电荷较少。综上所述，这些发现表明，非酶糖基化对CEP中葡萄糖的运输产生了负面影响，而不受基质孔隙率或SGAG含量的影响，这种影响可能是通过改变基质电荷密度来实现的。营养物质和代谢产物通过软骨终板(CEP)的运输不足可能是导致椎间盘退变的一个重要因素。以前的工作表明，CEP的传输特性取决于CEP基质的孔隙率，但对于CEP特性可能独立于孔隙率影响传输特性的作用知之甚少。本研究表明，非酶糖基化对CEP中葡萄糖的转运产生负面影响，而不受基质孔隙率或SGAG含量的影响，并且这种影响可能是通过改变基质电荷密度来实现的。
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. 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. 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. Inadequate nutrient and metabolite transport through the cartilage endplate (CEP) may be one important factor in the etiology of disc degeneration. 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. This study demonstrates 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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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：
3.7
作者：
Illien-Jünger S;Lu Y;Qureshi SA;Hecht AC;Cai W;Vlassara H;Striker GE;Iatridis JC
通讯作者：
Iatridis JC
饮食中晚期糖基化终产物的消耗导致小鼠椎间盘机械硬化。
影响因子：
4.3
作者：
Krishnamoorthy D;Hoy RC;Natelson DM;Torre OM;Laudier DM;Iatridis JC;Illien-Jünger S
通讯作者：
Illien-Jünger S
影响因子：
3.7
作者：
Dolor, Aaron;Sampson, Sara L.;Fields, Aaron J.
通讯作者：
Fields, Aaron J.
影响因子：
2.8
作者：
Bonnheim, Noah B.;Wang, Linshanshan;Lazar, Ann A.;Zhou, Jiamin;Chachad, Ravi;Sollmann, Nico;Guo, Xiaojie;Iriondo, Claudia;O'Neill, Conor;Lotz, Jeffrey C.;Link, Thomas M.;Krug, Roland;Fields, Aaron J.
通讯作者：
Fields, Aaron J.