Bone canonical Wnt signaling is downregulated in type 2 diabetes and associates with higher advanced glycation end-products (AGEs) content and reduced bone strength

Autor: Giulia Leanza, Francesca Cannata, Malak Faraj, Claudio Pedone, Viola Viola, Flavia Tramontana, Niccolò Pellegrini, Gianluca Vadalà, Alessandra Piccoli, Rocky Strollo, Francesca Zalfa, Alec T Beeve, Erica L Scheller, Simon Y Tang, Roberto Civitelli, Mauro Maccarrone, Rocco Papalia, Nicola Napoli
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: eLife, Vol 12 (2024)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.90437
Popis: Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOST and RUNX2) and advanced glycation end-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D (T2D 0.249% [0.156–0.366]) vs non-diabetic subjects 0.352% [0.269–0.454]; p=0.053, as well as reduced bone strength (T2D 21.60 MPa [13.46–30.10] vs non-diabetic subjects 76.24 MPa [26.81–132.9]; p=0.002). We also showed that gene expression of Wnt agonists LEF-1 (p=0.0136) and WNT10B (p=0.0302) were lower in T2D. Conversely, gene expression of WNT5A (p=0.0232), SOST (p
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