Effect of NF-кB Dependent Proinflammation on Osteogenic Differentiation of the Mesenchymal Stem Cells in Type 2 Diabetes

Study Overview
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Brief Summary
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This study determines whether NF-кB dependent proinflammatory state found in type 2 diabetes yield to a higher RAGE activation in the mesenchymal stem cell, as well as the effects of the proinflammation on osteoblast differentiation impairment and cellular apoptosis in type 2 diabetic patients. This study will compare non-diabetic control subjects and type 2 diabetic patients with metformin monotherapy failure in the aspect of 1) serum markers for NF-кB dependent proinflammatory state and its intracellular signals, 2) osteogenic differentiation and apoptosis of the mesenchymal stem cells, and 3) serum AGE, RAGE and cellular RAGE activation.

Detailed Description
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This study aims to explore whether proinflammation in type 2 diabetes is an mechanism underlined higher RAGE activation and osteoblast differentiation defect demonstrated in the MSC of type 2 diabetes, as well as the effects of the proinflammation on cellular differentiation and apoptosis of the MSC. Type 2 diabetes was known to be in proinflammatory state due to NF-кB-dependent cytokine secretion (for example, TNF-α, IL1 and IL6), which in turn contribute to NF-кB upregulation. Because RAGE expression is partly regulated by NF-кB signal, the NF-кB upregulation in proinflammatory state observed in type 2 diabetes may entail RAGE overactivation in this population. Therefore, the proinflammatory state and its correlation to cellular NF-кB-dependent RAGE activation is noteworthy to be determined in the MSC of type 2 diabetes. Furthermore, the effect of proinflammation on differentiation potential and apoptosis of the MSC in type 2 diabetes remains to be elucidated.

Official Title
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The Effect of NF-кB Dependent Proinflammation on the Overexpression of Receptor of Advanced Glycation End Products (RAGE) and the Osteogenic Differentiation Defect in the Mesenchymal Stem Cell-isolated From Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 2 diabetes who has HbA1c higher than 6.5% with metformin monotherapy and age-matched non-diabetes control subjects who signed consent form to be in the study. Exclusion Criteria: Patients who use thiazolidinedione, steroid, immunosuppressive medications, antiresorptive agents or anabolic therapy for osteoporosis. Patients with elevated serum creatinine higher than 1.4 in female and 1.5 in male. Patients with metastases cancer or hematologic malignancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non-diabetic controls<br>Age-matched non-diabetic subjects | |
| Type 2 diabetes<br>Type 2 diabetes with metformin monotherapy failure | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between NF-кB dependent-proinflammation markers and osteoblast-specific gene expression in the MSC to measure the effects of NF-кB dependent-proinflammation on differentiation potential toward osteoblast in type 2 diabetes. |  | 2-4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between NF-кB dependent-proinflammation markers and apoptotic marker expression in the MSC to measure effects of NF-кB dependent-proinflammation on cellular apoptosis in type 2 diabetes. |  | 2-4 weeks | 
| Correlation between NF-кB dependent-proinflammation markers and the expression of RAGE and its downstream signals in the MSC to measure effects of NF-кB dependent-proinflammation on cellular RAGE activation in type 2 diabetes. |  | 2-4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RAGE, Type 2 diabetes, osteoblast