Molecular signatures of bone remodeling imbalance in type 2 diabetes and osteoporosis comorbidity: a multi-omics study with in vivo support
Abstract
Type 2 diabetes (T2D) and osteoporosis (OP) frequently coexist, but the molecular features linking metabolic dysfunction to impaired bone remodeling remain incompletely defined. Here, we integrated public bulk transcriptomic datasets, a clinical serum proteomics cohort, and descriptive single-cell resources to prioritize candidates for investigation in a T2D-OP mouse model. The existing differential-expression screens, weighted gene co-expression network analysis (WGCNA) and set intersections nominated TTC1. A documented TTC1 expression-stratified GSEA in the low-versus-high BMD dataset was used for exploratory pathway context; it was not a disease-case-control enrichment analysis and did not apply a p-value adjustment method. These analyses are hypothesis-generating: TTC1 met the nominal screening criteria but did not meet BH-FDR < 0.05 in the low-versus-high BMD transcriptomic or serum proteomic results, and the T2D bulk analysis did not account for longitudinal sampling. Pre-imputation serum TTC1 measurements were available in only 1/14 controls and 6/14 patients, and TTC1 was excluded by detection-coverage filters. Single-cell analyses provided cellular context without cross-study disease-effect inference. In the T2D-OP mouse model, bone microstructural deterioration and histopathological damage were accompanied by increased TTC1, TNF-α, iNOS, NFATc1 and TRAP expression and reduced RUNX2 and OCN expression in bone tissue. The combined observations motivate further study of TTC1 in abnormal bone remodeling; independent clinical validation and functional perturbation are needed to establish its biological role.
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BibTeX
@article{zhao2026molecular,
title = {{Molecular signatures of bone remodeling imbalance in type 2 diabetes and osteoporosis comorbidity: a multi-omics study with in vivo support}},
author = {Yu Zhao and Tra My Nguyen and Fan Wang and Yijin Li and Zhicong Xia and Yueping Cai and Lihua Chen and Xiaosheng Lin},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-77685-1},
url = {https://www.nature.com/articles/s41598-026-77685-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular signatures of bone remodeling imbalance in type 2 diabetes and osteoporosis comorbidity: a multi-omics study with in vivo support
AU - Yu Zhao
AU - Tra My Nguyen
AU - Fan Wang
AU - Yijin Li
AU - Zhicong Xia
AU - Yueping Cai
AU - Lihua Chen
AU - Xiaosheng Lin
PY - 2026
DA - 2026/10/27
JO - Scientific Reports
DO - 10.1038/s41598-026-77685-1
UR - https://www.nature.com/articles/s41598-026-77685-1
AB - Type 2 diabetes (T2D) and osteoporosis (OP) frequently coexist, but the molecular features linking metabolic dysfunction to impaired bone remodeling remain incompletely defined. Here, we integrated public bulk transcriptomic datasets, a clinical serum proteomics cohort, and descriptive single-cell resources to prioritize candidates for investigation in a T2D-OP mouse model. The existing differential-expression screens, weighted gene co-expression network analysis (WGCNA) and set intersections nominated TTC1. A documented TTC1 expression-stratified GSEA in the low-versus-high BMD dataset was used for exploratory pathway context; it was not a disease-case-control enrichment analysis and did not apply a p-value adjustment method. These analyses are hypothesis-generating: TTC1 met the nominal screening criteria but did not meet BH-FDR < 0.05 in the low-versus-high BMD transcriptomic or serum proteomic results, and the T2D bulk analysis did not account for longitudinal sampling. Pre-imputation serum TTC1 measurements were available in only 1/14 controls and 6/14 patients, and TTC1 was excluded by detection-coverage filters. Single-cell analyses provided cellular context without cross-study disease-effect inference. In the T2D-OP mouse model, bone microstructural deterioration and histopathological damage were accompanied by increased TTC1, TNF-α, iNOS, NFATc1 and TRAP expression and reduced RUNX2 and OCN expression in bone tissue. The combined observations motivate further study of TTC1 in abnormal bone remodeling; independent clinical validation and functional perturbation are needed to establish its biological role.
SN - 2045-2322
ER -