Jae-Young Jung, Mohamed Habib, Luke J. Morrissette, Shannon C. Timmons, Tristan Maerz, Aaron J. Fields
{"title":"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","authors":"Jae-Young Jung, Mohamed Habib, Luke J. Morrissette, Shannon C. Timmons, Tristan Maerz, Aaron J. Fields","doi":"10.1002/jsp2.1297","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods and Results</h3>\n \n <p>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 (<i>p</i> = 0.04). These reductions in glucose uptake were observed in the absence of differences in CEP porosity (<i>p</i> = 0.89) or in the amounts of sulfated glycosaminoglycans (sGAGs, <i>p</i> = 0.47) or collagen (<i>p</i> = 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 (<i>p</i> = 0.02), implying the CEP matrix was less negatively charged.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1297","citationCount":"0","resultStr":"{\"title\":\"Non-enzymatic glycation reduces glucose transport in the human cartilage endplate independently of matrix porosity or proteoglycan content\",\"authors\":\"Jae-Young Jung, Mohamed Habib, Luke J. Morrissette, Shannon C. Timmons, Tristan Maerz, Aaron J. Fields\",\"doi\":\"10.1002/jsp2.1297\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods and Results</h3>\\n \\n <p>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 (<i>p</i> = 0.04). These reductions in glucose uptake were observed in the absence of differences in CEP porosity (<i>p</i> = 0.89) or in the amounts of sulfated glycosaminoglycans (sGAGs, <i>p</i> = 0.47) or collagen (<i>p</i> = 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 (<i>p</i> = 0.02), implying the CEP matrix was less negatively charged.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>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.</p>\\n </section>\\n </div>\",\"PeriodicalId\":14876,\"journal\":{\"name\":\"JOR Spine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2023-10-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1297\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JOR Spine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jsp2.1297\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ORTHOPEDICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JOR Spine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jsp2.1297","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}
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.