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

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02286128

Enrollment

Registered

2014-11-07

Start date

2014-11-30

Completion date

2018-05-03

Last updated

2018-07-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes

Keywords

Type 2 diabetes, RAGE, osteoblast

Brief summary

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

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.

Interventions

None listed

Study design

Observational model

CASE_CONTROL

Time perspective

CROSS_SECTIONAL

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	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

Measure	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

Countries

Thailand

Outcome results