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 Ca2+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 0.5 μM ATRA or 2.5 mM calcium, or both in combination for 14 days. Results: Higher intracellular Ca2+was observed in both Ca2+and Ca2+plus ATRA groups. Assessment of triglyceride content and glyceraldehyde 3-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 γ2 (PPARγ2) and glucose transferase-4 (GLUT4) in the treatment groups as compared with the control group. It is noteworthy that Ca2+plus ATRA treatment caused more significant effects on gene expression levels (P<0.05). Conclusion: In conclusion, combined treatment with Ca2+and ATRA has a more pronounced inhibitory effect on adipocyte differentiation, indicating their cumulative effect.