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Hedgehog proteins and parathyroid hormone‐related protein are involved in intervertebral disc maturation, degeneration, and calcification
Parathyroid hormone‐related protein (PTHrP) and hedgehog signaling play an important role in chondrocyte development, (hypertrophic) differentiation, and/or calcification, but their role in intervertebral disc (IVD) degeneration is unknown. Better understanding their involvement may provide therapeu...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920702/ https://www.ncbi.nlm.nih.gov/pubmed/31891120 http://dx.doi.org/10.1002/jsp2.1071 |
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author | Bach, Frances C. de Rooij, Kim M. Riemers, Frank M. Snuggs, Joseph W. de Jong, Willem A. M. Zhang, Ying Creemers, Laura B. Chan, Danny Le Maitre, Christine Tryfonidou, Marianna A. |
author_facet | Bach, Frances C. de Rooij, Kim M. Riemers, Frank M. Snuggs, Joseph W. de Jong, Willem A. M. Zhang, Ying Creemers, Laura B. Chan, Danny Le Maitre, Christine Tryfonidou, Marianna A. |
author_sort | Bach, Frances C. |
collection | PubMed |
description | Parathyroid hormone‐related protein (PTHrP) and hedgehog signaling play an important role in chondrocyte development, (hypertrophic) differentiation, and/or calcification, but their role in intervertebral disc (IVD) degeneration is unknown. Better understanding their involvement may provide therapeutic clues for low back pain due to IVD degeneration. Therefore, this study aimed to explore the role of PTHrP and hedgehog proteins in postnatal canine and human IVDs during the aging/degenerative process. The expression of PTHrP, hedgehog proteins and related receptors was studied during the natural loss of the notochordal cell (NC) phenotype during IVD maturation using tissue samples and de‐differentiation in vitro and degeneration by real‐time quantitative polymerase chain reaction (RT‐qPCR) and immunohistochemistry. Correlations between their expression and calcification levels (Alizarin Red S staining) were determined. In addition, the effect of PTHrP and hedgehog proteins on canine and human chondrocyte‐like cells (CLCs) was determined in vitro focusing on the propensity to induce calcification. The expression of PTHrP, its receptor (PTHR1) and hedgehog receptors decreased during loss of the NC phenotype. N‐terminal (active) hedgehog (Indian hedgehog/Sonic hedgehog) protein expression did not change during maturation or degeneration, whereas expression of PTHrP, PTHR1 and hedgehog receptors increased during IVD degeneration. Hedgehog and PTHR1 immunopositivity were increased in nucleus pulposus tissue with abundant vs no/low calcification. In vitro, hedgehog proteins facilitated calcification in CLCs, whereas PTHrP did not affect calcification levels. In conclusion, hedgehog and PTHrP expression is present in healthy and degenerated IVDs. Hedgehog proteins had the propensity to induce calcification in CLCs from degenerated IVDs, indicating that in the future, inhibiting hedgehog signaling could be an approach to inhibit calcification during IVD degeneration. |
format | Online Article Text |
id | pubmed-6920702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69207022019-12-30 Hedgehog proteins and parathyroid hormone‐related protein are involved in intervertebral disc maturation, degeneration, and calcification Bach, Frances C. de Rooij, Kim M. Riemers, Frank M. Snuggs, Joseph W. de Jong, Willem A. M. Zhang, Ying Creemers, Laura B. Chan, Danny Le Maitre, Christine Tryfonidou, Marianna A. JOR Spine Research Articles Parathyroid hormone‐related protein (PTHrP) and hedgehog signaling play an important role in chondrocyte development, (hypertrophic) differentiation, and/or calcification, but their role in intervertebral disc (IVD) degeneration is unknown. Better understanding their involvement may provide therapeutic clues for low back pain due to IVD degeneration. Therefore, this study aimed to explore the role of PTHrP and hedgehog proteins in postnatal canine and human IVDs during the aging/degenerative process. The expression of PTHrP, hedgehog proteins and related receptors was studied during the natural loss of the notochordal cell (NC) phenotype during IVD maturation using tissue samples and de‐differentiation in vitro and degeneration by real‐time quantitative polymerase chain reaction (RT‐qPCR) and immunohistochemistry. Correlations between their expression and calcification levels (Alizarin Red S staining) were determined. In addition, the effect of PTHrP and hedgehog proteins on canine and human chondrocyte‐like cells (CLCs) was determined in vitro focusing on the propensity to induce calcification. The expression of PTHrP, its receptor (PTHR1) and hedgehog receptors decreased during loss of the NC phenotype. N‐terminal (active) hedgehog (Indian hedgehog/Sonic hedgehog) protein expression did not change during maturation or degeneration, whereas expression of PTHrP, PTHR1 and hedgehog receptors increased during IVD degeneration. Hedgehog and PTHR1 immunopositivity were increased in nucleus pulposus tissue with abundant vs no/low calcification. In vitro, hedgehog proteins facilitated calcification in CLCs, whereas PTHrP did not affect calcification levels. In conclusion, hedgehog and PTHrP expression is present in healthy and degenerated IVDs. Hedgehog proteins had the propensity to induce calcification in CLCs from degenerated IVDs, indicating that in the future, inhibiting hedgehog signaling could be an approach to inhibit calcification during IVD degeneration. John Wiley & Sons, Inc. 2019-11-19 /pmc/articles/PMC6920702/ /pubmed/31891120 http://dx.doi.org/10.1002/jsp2.1071 Text en © 2019 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 Bach, Frances C. de Rooij, Kim M. Riemers, Frank M. Snuggs, Joseph W. de Jong, Willem A. M. Zhang, Ying Creemers, Laura B. Chan, Danny Le Maitre, Christine Tryfonidou, Marianna A. Hedgehog proteins and parathyroid hormone‐related protein are involved in intervertebral disc maturation, degeneration, and calcification |
title | Hedgehog proteins and parathyroid hormone‐related protein are involved in intervertebral disc maturation, degeneration, and calcification |
title_full | Hedgehog proteins and parathyroid hormone‐related protein are involved in intervertebral disc maturation, degeneration, and calcification |
title_fullStr | Hedgehog proteins and parathyroid hormone‐related protein are involved in intervertebral disc maturation, degeneration, and calcification |
title_full_unstemmed | Hedgehog proteins and parathyroid hormone‐related protein are involved in intervertebral disc maturation, degeneration, and calcification |
title_short | Hedgehog proteins and parathyroid hormone‐related protein are involved in intervertebral disc maturation, degeneration, and calcification |
title_sort | hedgehog proteins and parathyroid hormone‐related protein are involved in intervertebral disc maturation, degeneration, and calcification |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920702/ https://www.ncbi.nlm.nih.gov/pubmed/31891120 http://dx.doi.org/10.1002/jsp2.1071 |
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