ArticleBMC musculoskeletal disorders2022
Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy.
Article in BMC musculoskeletal disorders, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- The diabetic neuropathy and bone mineral density in type 2 diabetes mellitus: a cross-sectional and meta-analytic study.Clinical and experimental medicine · 2025Pooled it
- Clinical characteristics of the reduced bone mineral density subgroup among adults with type 2 diabetes mellitus: a retrospective cross-sectional study.BMC musculoskeletal disorders · 2026Article
- Diabetic Charcot Neuroarthropathy: A Contemporary Review of Molecular and Genetic Markers.Foot & ankle international · 2026Review
- PRKD2 as a novel target for targeting the diabetes-osteoporosis nexus.Scientific reports · 2025Article
- The Role of Wnt3a/β-Catenin/TCF7L2 Pathway in Diabetes and Cardiorenal Complications.Cardiorenal medicine · 2025Review
- PATHOGENESIS OF ACUTE DIABETIC CHARCOT ARTHROPATHY IN THE FOOT AND ANKLE: A COMPREHENSIVE LITERATURE REVIEW.Orthopedic reviews · 2025Article
- The role of wnt signaling in diabetes-induced osteoporosis.Diabetology & metabolic syndrome · 2023Review
- The complex pathophysiology of bone fragility in obesity and type 2 diabetes mellitus: therapeutic targets to promote osteogenesis.Frontiers in endocrinology · 2023Review
- Decoding Chronic Charcot Arthropathy: Molecular Mechanisms, Predictive Biomarkers, and Emerging Therapies.JB & JS open accessReview
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundType 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.
methodsBone 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).
resultsIn 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).
conclusionsFor 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.
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