High Glucose Level Impairs Human Mature Bone Marrow Adipocyte Function Through Increased ROS Production.

Area of Science:

• Cell Biology
• Metabolic Diseases
• Bone Biology

Background:

• Bone marrow adipocytes (BMAds) increase in aging, menopause, and metabolic diseases like Type 2 diabetes.
• Osteoporotic conditions are linked to oxidative stress and hyperglycemia, contributing to bone fragility.
• Excess glucose and reactive oxygen species (ROS) promote adipogenesis over osteoblastogenesis.

Purpose of the Study:

• To investigate if high glucose exposure induces dysfunction in mature BMAds via ROS production.
• To examine the effects of high glucose on human bone mesenchymal stromal cells (hBMSCs) during differentiation and in mature adipocytes.

Main Methods:

• hBMSCs were cultured under low (LG, 5 mM) and high glucose (HG, 25 mM) conditions during differentiation and for 21 days post-differentiation.
• mRNA expression of adipogenic and ROS metabolism genes (PPARG, CEBPA, adiponectin, leptin, NOX4) was analyzed.
• Intracellular and extracellular ROS levels were measured using Amplex Red assay.

Main Results:

• HG did not affect initial adipocyte differentiation but decreased PPARG, CEBPA, and adiponectin mRNA after 21 days.
• Mature BMAds under HG showed a 50% increase in ROS production, linked to upregulated NOX4 mRNA.
• Pro-oxidant treatment under LG mimicked HG's effect on gene expression, and amplified HG's impact.

Conclusions:

• High glucose concentrations induce dysfunction in mature BMAds, characterized by altered adipokine/transcription factor expression and increased ROS.
• Enhanced NOX4 expression likely mediates the ROS increase under high glucose conditions.
• Mature BMAds are sensitive to glucose and ROS levels, impacting their function in osteoporosis associated with aging and metabolic diseases.