Low bone turnover is associated with advanced glycation end-products, oxidative stress, and inflammation induced by
Peipei Shi1, He Gong1, Linwei Lyu2
1Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
Abstract:
Type 2 diabetes mellitus (T2DM) can lead to multiple complications. T2DM-related bone damage has been linked to abnormal bone turnover, but it cannot fully explain the mechanisms of T2DM bone disease. This study attempts to elucidate the underlying mechanisms of poor bone quality in T2DM. Hence, T2DM model was induced by a high-fat diet combined with a single streptozotocin injection in 7-week-old male SD rats. Osteoblasts derived from SD rats were cultured in high glucose to mimic hyperglycemia. Low bone turnover was observed in T2DM bone with elevated levels of advanced glycation end-products (AGEs) and receptor for AGEs (RAGE). Additionally, higher levels of oxidative stress and inflammatory factors were found in T2DM bone. AGEs content in bone was pairwise correlated with RAGE, hydrogen peroxide, and inflammatory factors. Serum levels of RAGE, oxidative stress, and inflammatory factors were higher in T2DM, while AGEs content tended to be lower. Besides, 35 differentially expressed metabolites were screened in T2DM serum. Osteoblasts exposed to high glucose displayed analogous abnormal changes in these biomarkers. Thus, low bone turnover in T2DM might be partially due to excess oxidative stress and inflammation induced by AGE-RAGE signaling. Furthermore, these biomarker levels in serum were mostly consistent with bone, demonstrating their possibility for predicting bone quality in T2DM.
Insights
Type 2 diabetes causes poor bone quality through advanced glycation end-products (AGEs) and receptor for AGEs (RAGE) signaling, increasing oxidative stress and inflammation. Serum biomarkers may predict bone health in diabetic patients.
Area of Science:
- Endocrinology
- Bone Biology
- Metabolic Diseases
Background:
- Type 2 diabetes mellitus (T2DM) is associated with bone complications.
- Existing explanations for T2DM bone disease, like abnormal bone turnover, are insufficient.
- The precise mechanisms underlying poor bone quality in T2DM require further elucidation.
Purpose of the Study:
- To investigate the mechanisms contributing to poor bone quality in T2DM.
- To explore the role of advanced glycation end-products (AGEs) and their receptor (RAGE) signaling in T2DM bone disease.
- To identify potential serum biomarkers for predicting bone quality in T2DM.
Main Methods:
- A T2DM rat model was established using a high-fat diet and streptozotocin injection.
- Primary osteoblasts were cultured under high glucose conditions to simulate hyperglycemia.
- Levels of AGEs, RAGE, oxidative stress markers (hydrogen peroxide), inflammatory factors, and metabolites were measured in bone and serum.
- Correlations between biomarkers and differentially expressed metabolites were analyzed.
Main Results:
- T2DM bone exhibited low turnover with elevated AGEs and RAGE.
- Increased oxidative stress and inflammatory factors were detected in T2DM bone.
- AGEs content in bone correlated positively with RAGE, hydrogen peroxide, and inflammatory factors.
- Serum RAGE, oxidative stress, and inflammatory markers were elevated in T2DM, while serum AGEs were lower.
- Osteoblasts cultured in high glucose showed similar biomarker abnormalities.
- 35 differentially expressed serum metabolites were identified in T2DM rats.
Conclusions:
- AGE-RAGE signaling contributes to low bone turnover in T2DM via oxidative stress and inflammation.
- Serum levels of RAGE, oxidative stress, and inflammatory factors may serve as predictive biomarkers for bone quality in T2DM.
- Metabolomic analysis revealed distinct profiles in T2DM serum, potentially linked to bone health.
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