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

• DOI: 10.7554/elife.90437.3
• Publication Date: 2024-04-10T15:00:53Z
• Authors: 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
• Keywords: Sclerostin; Bone remodeling; Advanced glycation end-product; LRP5; RUNX2

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that formation genes ( SOST and RUNX2 ) advanced glycation end-products (AGEs) were impaired in T2D. investigated Wnt signaling regulation its association AGEs accumulation strength T2D from tissue of 15 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend low mineralized volume (T2D 0.249% [0.156–0.366]) vs subjects 0.352% [0.269–0.454]; p=0.053, as well reduced 21.60 MPa [13.46–30.10] 76.24 [26.81–132.9]; p=0.002). also showed gene expression agonists LEF-1 (p=0.0136) WNT10B (p=0.0302) lower Conversely, WNT5A (p=0.0232), (p<0.0001), GSK3B (p=0.0456) higher, while collagen COL1A1 was (p=0.0482). content (r=0.9231, p<0.0001; r=0.6751, p=0.0322), but inversely correlated (r=–0.7500, p=0.0255; r=–0.9762, p=0.0004). glycemic control disease duration (r=0.4846, p=0.0043; r=0.7107, p=0.00174), whereas only (r=0.5589, p=0.0037; r=0.4901, p=0.0051). Finally, Young’s modulus negatively (r=−0.5675, p=0.0011), AXIN2 (r=−0.5523, p=0.0042), SFRP5 (r=−0.4442, p=0.0437), positively (r=0.4116, p=0.0295) (r=0.6697, p=0.0001). These findings suggest could be the main determinants fragility