Increased bone inflammation in type 2 diabetes and obesity correlates with Wnt signaling downregulation and reduced bone strength

• DOI: 10.7554/elife.102146.1
• Publication Date: 2024-11-21T15:25:19Z
• Authors: Giulia Leanza; Malak Faraj; Francesca Cannata; Viola Viola; Niccolò Pellegrini; Flavia Tramontana; Claudio Pedone; Gianluca Vadalà; Alessandra Piccoli; Rocky Strollo; Francesca Zalfa; Roberto Civitelli; Mauro Maccarrone; Rocco Papalia; Nicola Napoli
• Keywords: Sclerostin

Type 2 diabetes (T2D) and obesity (OB) are associated with chronic low-grade inflammation increased fracture risk. In vitro studies showed that induces bone erosion inhibits formation by increasing Wnt canonical pathway inhibitors. However, the impact of on regulation quality in T2D OB remains unclear. To this end, we studied 63 postmenopausal women (age >65 years) undergoing hip replacement for osteoarthritis. Among these women, 19 had (HbA1c 6.8±0.79%; BMI 29.9±5.2 kg/m2), 17 but they were normoglycemic (BMI 32.5±5.4 27 served as controls 23.1±5.5 kg/m2). Serum inflammatory cytokines automated immunoassay (ELLA), revealed higher TNF-α (p=0.0084) lower adiponectin (p=0.0402) T2D, IL-6 (p=0.0003) levels vs controls. Gene expression analysis trabecular (p=0.0019) SFRP5 IL-10 was both (p=0.0285), (p=0.0324), while (ADIPOQ) only (p=0.0041) Interestingly, inhibitor SOST (p<0.0001) Conversely, WNT10B mRNA (p=0.0071) (p=0.0196) controls, LEF-1 (p=0.0009). WNT5A (p=0.0025) GSK3β Importantly, positively correlated (r=0.5121, p=0.0002), (r=0.3227, p=0.0396) (r=0.3789, p=0.0146) levels, negatively (r=0.3844, p=0.0188) LEF-1(r=-0.3310, p=0.0322) levels. (r=0.3100, p=0.0457). ADIPOQ (r=-0.3864, p=0.0105) (r=-0.3025, p=0.0515) Moreover, (r=0.3991, p=0.0131). Finally, serum (r=-0.3473, p=0.0352) (r=-0.3777, p=0.0302) Young’s Modulus, an index strength. These findings suggest subjects is strength, shedding light pathophysiology impairment obesity.