Wnt Signaling Regulation in Bone of Postmenopausal Women With Type 2 Diabetes

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. Thus, we investigated Wnt signaling regulation and its association with AGEs accumulation in T2D. We obtained bone tissue from 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D. We showed that gene expression of Wnt agonists LEF-1 and WNT10B were lower in T2D. Accordingly, WNT5A and SOST gene expression were higher, while collagen (COL1A1) was lower in T2D. Importantly, AGEs content was associated with SOST and WNT5A, but inversely correlated with LEF-1 and COL1A1. Finally, SOST was also associated with glycemic control and disease duration. These findings suggest that Wnt signaling and AGEs could be the main determinants of bone fragility in T2D. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by an internal grant of Campus Bio-Medico University of Rome ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Campus Bio-Medico University of Rome (Protocol name: "Evaluation of bone strength and Wnt pathway in obese patients", approved on 26/10/2015). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data are available upon request to the corresponding authors