Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: BMC Musculoskeletal Disorders, Vol 23, Iss 1, Pp 1-10 (2022)
Druh dokumentu: article
ISSN: 1471-2474
DOI: 10.1186/s12891-022-05314-9
Popis: 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
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