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Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy
BACKGROUND: Type 2 diabetes mellitus (T2DM) patients show a markedly higher fracture risk and impaired fracture healing when compared to non-diabetic patients. However in contrast to type 1 diabetes mellitus, bone mineral density in T2DM is known to be normal or even regionally elevated, also known...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017014/ https://www.ncbi.nlm.nih.gov/pubmed/35436882 http://dx.doi.org/10.1186/s12891-022-05314-9 |
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author | Gassel, Laurens Christian Schneider, Sandra Banke, Ingo Jörg Braun, Karl Friedrich Volkering, Christoph Zeeb, Leonie Burgkart, Rainer Hans Hermann von Eisenhart-Rothe, Rüdiger Biberthaler, Peter van Griensven, Martijn Haug, Alexander Tobias |
author_facet | Gassel, Laurens Christian Schneider, Sandra Banke, Ingo Jörg Braun, Karl Friedrich Volkering, Christoph Zeeb, Leonie Burgkart, Rainer Hans Hermann von Eisenhart-Rothe, Rüdiger Biberthaler, Peter van Griensven, Martijn Haug, Alexander Tobias |
author_sort | Gassel, Laurens Christian |
collection | PubMed |
description | BACKGROUND: Type 2 diabetes mellitus (T2DM) patients show a markedly higher fracture risk and impaired fracture healing when compared to non-diabetic patients. However in contrast to type 1 diabetes mellitus, bone mineral density in T2DM is known to be normal or even regionally elevated, also known as diabetic bone disease. Charcot arthropathy is a severe and challenging complication leading to bone destruction and mutilating bone deformities. Wnt signaling is involved in increasing bone mineral density, bone homeostasis and apoptotic processes. It has been shown that type 2 diabetes mellitus is strongly associated with gene variants of the Wnt signaling pathway, specifically polymorphisms of TCF7L2 (transcription factor 7 like 2), which is an effector transcription factor of this pathway. METHODS: Bone samples of 19 T2DM patients and 7 T2DM patients with additional Charcot arthropathy were compared to 19 non-diabetic controls. qPCR analysis for selected members of the Wnt-signaling pathway (WNT3A, WNT5A, catenin beta, TCF7L2) and bone gamma-carboxyglutamate (BGLAP, Osteocalcin) was performed and analyzed using the 2-ΔΔCt- Method. Statistical analysis comprised one-way analysis of variance (ANOVA). RESULTS: In T2DM patients who had developed Charcot arthropathy WNT3A and WNT5A gene expression was down-regulated by 89 and 58% compared to healthy controls (p < 0.0001). TCF7L2 gene expression showed a significant reduction by 63% (p < 0.0001) and 18% (p = 0.0136) in diabetic Charcot arthropathy. In all diabetic patients BGLAP (Osteocalcin) was significantly decreased by at least 59% (p = 0.0019). CONCLUSIONS: For the first time with this study downregulation of members of the Wnt-signaling pathway has been shown in the bone of diabetic patients with and without Charcot arthropathy. This may serve as future therapeutic target for this severe disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-022-05314-9. |
format | Online Article Text |
id | pubmed-9017014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-90170142022-04-20 Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy Gassel, Laurens Christian Schneider, Sandra Banke, Ingo Jörg Braun, Karl Friedrich Volkering, Christoph Zeeb, Leonie Burgkart, Rainer Hans Hermann von Eisenhart-Rothe, Rüdiger Biberthaler, Peter van Griensven, Martijn Haug, Alexander Tobias BMC Musculoskelet Disord Research BACKGROUND: Type 2 diabetes mellitus (T2DM) patients show a markedly higher fracture risk and impaired fracture healing when compared to non-diabetic patients. However in contrast to type 1 diabetes mellitus, bone mineral density in T2DM is known to be normal or even regionally elevated, also known as diabetic bone disease. Charcot arthropathy is a severe and challenging complication leading to bone destruction and mutilating bone deformities. Wnt signaling is involved in increasing bone mineral density, bone homeostasis and apoptotic processes. It has been shown that type 2 diabetes mellitus is strongly associated with gene variants of the Wnt signaling pathway, specifically polymorphisms of TCF7L2 (transcription factor 7 like 2), which is an effector transcription factor of this pathway. METHODS: Bone samples of 19 T2DM patients and 7 T2DM patients with additional Charcot arthropathy were compared to 19 non-diabetic controls. qPCR analysis for selected members of the Wnt-signaling pathway (WNT3A, WNT5A, catenin beta, TCF7L2) and bone gamma-carboxyglutamate (BGLAP, Osteocalcin) was performed and analyzed using the 2-ΔΔCt- Method. Statistical analysis comprised one-way analysis of variance (ANOVA). RESULTS: In T2DM patients who had developed Charcot arthropathy WNT3A and WNT5A gene expression was down-regulated by 89 and 58% compared to healthy controls (p < 0.0001). TCF7L2 gene expression showed a significant reduction by 63% (p < 0.0001) and 18% (p = 0.0136) in diabetic Charcot arthropathy. In all diabetic patients BGLAP (Osteocalcin) was significantly decreased by at least 59% (p = 0.0019). CONCLUSIONS: For the first time with this study downregulation of members of the Wnt-signaling pathway has been shown in the bone of diabetic patients with and without Charcot arthropathy. This may serve as future therapeutic target for this severe disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-022-05314-9. BioMed Central 2022-04-18 /pmc/articles/PMC9017014/ /pubmed/35436882 http://dx.doi.org/10.1186/s12891-022-05314-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Gassel, Laurens Christian Schneider, Sandra Banke, Ingo Jörg Braun, Karl Friedrich Volkering, Christoph Zeeb, Leonie Burgkart, Rainer Hans Hermann von Eisenhart-Rothe, Rüdiger Biberthaler, Peter van Griensven, Martijn Haug, Alexander Tobias Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy |
title | Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy |
title_full | Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy |
title_fullStr | Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy |
title_full_unstemmed | Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy |
title_short | Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy |
title_sort | dysregulation of wnt signaling in bone of type 2 diabetes mellitus and diabetic charcot arthropathy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017014/ https://www.ncbi.nlm.nih.gov/pubmed/35436882 http://dx.doi.org/10.1186/s12891-022-05314-9 |
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