Dietary advanced glycation end-product consumption leads to mechanical stiffening of murine intervertebral discs
Back pain is a leading cause of disability and is strongly associated with intervertebral disc (IVD) degeneration. Reducing structural disruption and catabolism in IVD degeneration remains an important clinical challenge. Pro-oxidant and structure-modifying advanced glycation end-products (AGEs) con...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2018-12-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/11/12/dmm036012 |
| _version_ | 1811279067499986944 |
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| author | Divya Krishnamoorthy Robert C. Hoy Devorah M. Natelson Olivia M. Torre Damien M. Laudier James C. Iatridis Svenja Illien-Jünger |
| author_facet | Divya Krishnamoorthy Robert C. Hoy Devorah M. Natelson Olivia M. Torre Damien M. Laudier James C. Iatridis Svenja Illien-Jünger |
| author_sort | Divya Krishnamoorthy |
| collection | DOAJ |
| description | Back pain is a leading cause of disability and is strongly associated with intervertebral disc (IVD) degeneration. Reducing structural disruption and catabolism in IVD degeneration remains an important clinical challenge. Pro-oxidant and structure-modifying advanced glycation end-products (AGEs) contribute to obesity and diabetes, which are associated with increased back pain, and accumulate in tissues due to hyperglycemia or ingestion of foods processed at high heat. Collagen-rich IVDs are particularly susceptible to AGE accumulation due to their slow metabolic rates, yet it is unclear whether dietary AGEs can cross the endplates to accumulate in IVDs. A dietary mouse model was used to test the hypothesis that chronic consumption of high AGE diets results in sex-specific IVD structural disruption and functional changes. High AGE diet resulted in AGE accumulation in IVDs and increased IVD compressive stiffness, torque range and failure torque, particularly for females. These biomechanical changes were likely caused by significantly increased AGE crosslinking in the annulus fibrosus, measured by multiphoton imaging. Increased collagen damage measured with collagen hybridizing peptide did not appear to influence biomechanical properties and may be a risk factor as these animals age. The greater influence of high AGE diet on females is an important area of future investigation that may involve AGE receptors known to interact with estrogen. We conclude that high AGE diets can be a source for IVD crosslinking and collagen damage known to be important in IVD degeneration. Dietary modifications and interventions that reduce AGEs warrant further investigation and may be particularly important for diabetics, in whom AGEs accumulate more rapidly. |
| first_indexed | 2024-04-13T00:48:07Z |
| format | Article |
| id | doaj.art-c0b99b40da8241b3acb5ad2e352222ae |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-04-13T00:48:07Z |
| publishDate | 2018-12-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-c0b99b40da8241b3acb5ad2e352222ae2022-12-22T03:09:57ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112018-12-01111210.1242/dmm.036012036012Dietary advanced glycation end-product consumption leads to mechanical stiffening of murine intervertebral discsDivya Krishnamoorthy0Robert C. Hoy1Devorah M. Natelson2Olivia M. Torre3Damien M. Laudier4James C. Iatridis5Svenja Illien-Jünger6 Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Back pain is a leading cause of disability and is strongly associated with intervertebral disc (IVD) degeneration. Reducing structural disruption and catabolism in IVD degeneration remains an important clinical challenge. Pro-oxidant and structure-modifying advanced glycation end-products (AGEs) contribute to obesity and diabetes, which are associated with increased back pain, and accumulate in tissues due to hyperglycemia or ingestion of foods processed at high heat. Collagen-rich IVDs are particularly susceptible to AGE accumulation due to their slow metabolic rates, yet it is unclear whether dietary AGEs can cross the endplates to accumulate in IVDs. A dietary mouse model was used to test the hypothesis that chronic consumption of high AGE diets results in sex-specific IVD structural disruption and functional changes. High AGE diet resulted in AGE accumulation in IVDs and increased IVD compressive stiffness, torque range and failure torque, particularly for females. These biomechanical changes were likely caused by significantly increased AGE crosslinking in the annulus fibrosus, measured by multiphoton imaging. Increased collagen damage measured with collagen hybridizing peptide did not appear to influence biomechanical properties and may be a risk factor as these animals age. The greater influence of high AGE diet on females is an important area of future investigation that may involve AGE receptors known to interact with estrogen. We conclude that high AGE diets can be a source for IVD crosslinking and collagen damage known to be important in IVD degeneration. Dietary modifications and interventions that reduce AGEs warrant further investigation and may be particularly important for diabetics, in whom AGEs accumulate more rapidly.http://dmm.biologists.org/content/11/12/dmm036012SpineIntervertebral disc degenerationDiabetesAdvanced glycation end-productsDiet |
| spellingShingle | Divya Krishnamoorthy Robert C. Hoy Devorah M. Natelson Olivia M. Torre Damien M. Laudier James C. Iatridis Svenja Illien-Jünger Dietary advanced glycation end-product consumption leads to mechanical stiffening of murine intervertebral discs Disease Models & Mechanisms Spine Intervertebral disc degeneration Diabetes Advanced glycation end-products Diet |
| title | Dietary advanced glycation end-product consumption leads to mechanical stiffening of murine intervertebral discs |
| title_full | Dietary advanced glycation end-product consumption leads to mechanical stiffening of murine intervertebral discs |
| title_fullStr | Dietary advanced glycation end-product consumption leads to mechanical stiffening of murine intervertebral discs |
| title_full_unstemmed | Dietary advanced glycation end-product consumption leads to mechanical stiffening of murine intervertebral discs |
| title_short | Dietary advanced glycation end-product consumption leads to mechanical stiffening of murine intervertebral discs |
| title_sort | dietary advanced glycation end product consumption leads to mechanical stiffening of murine intervertebral discs |
| topic | Spine Intervertebral disc degeneration Diabetes Advanced glycation end-products Diet |
| url | http://dmm.biologists.org/content/11/12/dmm036012 |
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