Attenuation of Differentiation of Mesenchymal Stem Cells Into Adipocytes by Co-administration of Calcium and All-trans Retinoic Acid

Background: Adipogenesis is affected by multiple factors, among which all-trans retinoic acid (ATRA) and Ca۲+are considered important factors. Objectives: This study aimed to evaluate the effect of calcium, ATRA, and their underlying molecular mechanisms, alone and in combination, on adipocyte differentiation. Methods: Human adipose-derived mesenchymal stem cells (hAD-MSCs) were differentiated into adipocytes and simultaneously exposed to ۰.۵ μM ATRA or ۲.۵ mM calcium, or both in combination for ۱۴ days. Results: Higher intracellular Ca۲+was observed in both Ca۲+and Ca۲+plus ATRA groups. Assessment of triglyceride content and glyceraldehyde ۳-phosphate dehydrogenase (GAPDH) activity indicated lower differentiation levels in all treatment groups than in the control group. Furthermore, the results demonstrated a higher expression of retinoic acid receptor alpha (RAR-α) and lower expression of peroxisome proliferator-activated receptor γ۲ (PPARγ۲) and glucose transferase-۴ (GLUT۴) in the treatment groups as compared with the control group. It is noteworthy that Ca۲+plus ATRA treatment caused more significant effects on gene expression levels (P<۰.۰۵). Conclusion: In conclusion, combined treatment with Ca۲+and ATRA has a more pronounced inhibitory effect on adipocyte differentiation, indicating their cumulative effect.