Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy
Abstract 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, als...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | BMC Musculoskeletal Disorders |
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| Online Access: | https://doi.org/10.1186/s12891-022-05314-9 |
| _version_ | 1818278987921620992 |
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| author | Laurens Christian Gassel Sandra Schneider Ingo Jörg Banke Karl Friedrich Braun Christoph Volkering Leonie Zeeb Rainer Hans Hermann Burgkart Rüdiger von Eisenhart-Rothe Peter Biberthaler Martijn van Griensven Alexander Tobias Haug |
| author_facet | Laurens Christian Gassel Sandra Schneider Ingo Jörg Banke Karl Friedrich Braun Christoph Volkering Leonie Zeeb Rainer Hans Hermann Burgkart Rüdiger von Eisenhart-Rothe Peter Biberthaler Martijn van Griensven Alexander Tobias Haug |
| author_sort | Laurens Christian Gassel |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T23:26:10Z |
| format | Article |
| id | doaj.art-d9104605fe9d402b96d1eaf9c343b629 |
| institution | Directory Open Access Journal |
| issn | 1471-2474 |
| language | English |
| last_indexed | 2024-12-12T23:26:10Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Musculoskeletal Disorders |
| spelling | doaj.art-d9104605fe9d402b96d1eaf9c343b6292022-12-22T00:08:05ZengBMCBMC Musculoskeletal Disorders1471-24742022-04-0123111010.1186/s12891-022-05314-9Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathyLaurens Christian Gassel0Sandra Schneider1Ingo Jörg Banke2Karl Friedrich Braun3Christoph Volkering4Leonie Zeeb5Rainer Hans Hermann Burgkart6Rüdiger von Eisenhart-Rothe7Peter Biberthaler8Martijn van Griensven9Alexander Tobias Haug10Department of Experimental Trauma Surgery, and Department of Surgery, Klinikum rechts der Isar, Technical University of MunichDepartment of Experimental Trauma Surgery, and Department of Surgery, Klinikum rechts der Isar, Technical University of MunichDepartment of Orthopedics and Sports Orthopedics, Klinikum rechts der Isar, Technical University of MunichCharité – Berlin University of Medicine, Center for Musculoskeletal Surgery, Campus Virchow-Klinikum (CVK)OrthoevoDepartment of Experimental Trauma Surgery, and Department of Surgery, Klinikum rechts der Isar, Technical University of MunichDepartment of Orthopedics and Sports Orthopedics, Klinikum rechts der Isar, Technical University of MunichDepartment of Orthopedics and Sports Orthopedics, Klinikum rechts der Isar, Technical University of MunichDepartment of Trauma Surgery, Klinikum rechts der Isar, Technical University of MunichDepartment of Experimental Trauma Surgery, and Department of Surgery, Klinikum rechts der Isar, Technical University of MunichDepartment of Experimental Trauma Surgery and, Department of Orthopedics and Sports Orthopedics, Klinikum rechts der Isar, Technical University of MunichAbstract 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.https://doi.org/10.1186/s12891-022-05314-9Diabetic bone diseaseType 2 diabetes mellitusWnt signalingTCF7L2Osteocalcin |
| spellingShingle | Laurens Christian Gassel Sandra Schneider Ingo Jörg Banke Karl Friedrich Braun Christoph Volkering Leonie Zeeb Rainer Hans Hermann Burgkart Rüdiger von Eisenhart-Rothe Peter Biberthaler Martijn van Griensven Alexander Tobias Haug Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy BMC Musculoskeletal Disorders Diabetic bone disease Type 2 diabetes mellitus Wnt signaling TCF7L2 Osteocalcin |
| 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 | Diabetic bone disease Type 2 diabetes mellitus Wnt signaling TCF7L2 Osteocalcin |
| url | https://doi.org/10.1186/s12891-022-05314-9 |
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