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Degenerate intervertebral disc‐like pH induces a catabolic mechanoresponse in human nucleus pulposus cells
Mechanical stimulation is known to influence intervertebral disc (IVD) cell behavior and function, but the effect on disc cells is routinely considered in isolation from other microenvironmental factors. Acidic pH has been shown to be a prominent and detrimental microenvironmental factor present in...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711490/ https://www.ncbi.nlm.nih.gov/pubmed/31463436 http://dx.doi.org/10.1002/jsp2.1004 |
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author | Hodson, Nathan W. Patel, Sonal Richardson, Stephen M. Hoyland, Judith A. Gilbert, Hamish T. J. |
author_facet | Hodson, Nathan W. Patel, Sonal Richardson, Stephen M. Hoyland, Judith A. Gilbert, Hamish T. J. |
author_sort | Hodson, Nathan W. |
collection | PubMed |
description | Mechanical stimulation is known to influence intervertebral disc (IVD) cell behavior and function, but the effect on disc cells is routinely considered in isolation from other microenvironmental factors. Acidic pH has been shown to be a prominent and detrimental microenvironmental factor present in degenerate IVDs, but its influence on the human disc cell mechanoresponse has never been studied. We investigated the response of agarose‐encapsulated human nucleus pulposus (NP) cells to 0.004 MPa, 1.0 Hz and 1 hour of compression (Flexcell FX4000 Compression System) under pH conditions representative of nondegenerate (pH 7.1) and degenerate (pH 6.5) IVDs. Cell viability, extracellular matrix production, and expression of anabolic/anti‐catabolic and catabolic genes were assessed. We report that preculture of NP cells in agarose gels was required in order for cells to be mechanoresponsive, and this correlated with increased type VI collagen, α5β1 integrin, and fibronectin expression. Furthermore, the matrix homeostatic response observed at pH 7.1 (representative of nondegenerate IVDs; increased aggrecan [AGC], tissue inhibitor of metalloproteinases‐1 [TIMP1], matrix metalloproteinase‐3 [MMP3], a disintegrin and metalloproteinase with thrombospondin motif‐5 [ADAMTS5] gene expression) was RGD‐integrin dependent, whereas only MMP3 remained mechanoresponsive at pH 6.5, and this was independent of RGD‐integrins. Our findings suggest differential mechanotransduction pathways operating for specific genes, with RGD‐integrin dependent AGC expression, but not RGD‐independent MMP3 expression, inhibited at pH representative of degenerate IVDs (pH 6.5), which could contribute to the catabolic phenotype observed during IVD degeneration. CLINICAL SIGNIFICANCE: Characterizing the influence of the mechanical and chemical intervertebral disc microenvironment on disc cells, particularly in disc degeneration, could help develop future therapeutic strategies for the treatment of discogenic back pain. |
format | Online Article Text |
id | pubmed-6711490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67114902019-08-28 Degenerate intervertebral disc‐like pH induces a catabolic mechanoresponse in human nucleus pulposus cells Hodson, Nathan W. Patel, Sonal Richardson, Stephen M. Hoyland, Judith A. Gilbert, Hamish T. J. JOR Spine Research Articles Mechanical stimulation is known to influence intervertebral disc (IVD) cell behavior and function, but the effect on disc cells is routinely considered in isolation from other microenvironmental factors. Acidic pH has been shown to be a prominent and detrimental microenvironmental factor present in degenerate IVDs, but its influence on the human disc cell mechanoresponse has never been studied. We investigated the response of agarose‐encapsulated human nucleus pulposus (NP) cells to 0.004 MPa, 1.0 Hz and 1 hour of compression (Flexcell FX4000 Compression System) under pH conditions representative of nondegenerate (pH 7.1) and degenerate (pH 6.5) IVDs. Cell viability, extracellular matrix production, and expression of anabolic/anti‐catabolic and catabolic genes were assessed. We report that preculture of NP cells in agarose gels was required in order for cells to be mechanoresponsive, and this correlated with increased type VI collagen, α5β1 integrin, and fibronectin expression. Furthermore, the matrix homeostatic response observed at pH 7.1 (representative of nondegenerate IVDs; increased aggrecan [AGC], tissue inhibitor of metalloproteinases‐1 [TIMP1], matrix metalloproteinase‐3 [MMP3], a disintegrin and metalloproteinase with thrombospondin motif‐5 [ADAMTS5] gene expression) was RGD‐integrin dependent, whereas only MMP3 remained mechanoresponsive at pH 6.5, and this was independent of RGD‐integrins. Our findings suggest differential mechanotransduction pathways operating for specific genes, with RGD‐integrin dependent AGC expression, but not RGD‐independent MMP3 expression, inhibited at pH representative of degenerate IVDs (pH 6.5), which could contribute to the catabolic phenotype observed during IVD degeneration. CLINICAL SIGNIFICANCE: Characterizing the influence of the mechanical and chemical intervertebral disc microenvironment on disc cells, particularly in disc degeneration, could help develop future therapeutic strategies for the treatment of discogenic back pain. John Wiley & Sons, Inc. 2018-03-11 /pmc/articles/PMC6711490/ /pubmed/31463436 http://dx.doi.org/10.1002/jsp2.1004 Text en © 2018 The Authors. JOR Spine published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Hodson, Nathan W. Patel, Sonal Richardson, Stephen M. Hoyland, Judith A. Gilbert, Hamish T. J. Degenerate intervertebral disc‐like pH induces a catabolic mechanoresponse in human nucleus pulposus cells |
title | Degenerate intervertebral disc‐like pH induces a catabolic mechanoresponse in human nucleus pulposus cells |
title_full | Degenerate intervertebral disc‐like pH induces a catabolic mechanoresponse in human nucleus pulposus cells |
title_fullStr | Degenerate intervertebral disc‐like pH induces a catabolic mechanoresponse in human nucleus pulposus cells |
title_full_unstemmed | Degenerate intervertebral disc‐like pH induces a catabolic mechanoresponse in human nucleus pulposus cells |
title_short | Degenerate intervertebral disc‐like pH induces a catabolic mechanoresponse in human nucleus pulposus cells |
title_sort | degenerate intervertebral disc‐like ph induces a catabolic mechanoresponse in human nucleus pulposus cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711490/ https://www.ncbi.nlm.nih.gov/pubmed/31463436 http://dx.doi.org/10.1002/jsp2.1004 |
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