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Abstract

BACKGROUND:

Our previous studies have demonstrated that melatonin inhibits the adipogenic differentiation of bone marrow mesenchymal stem cells. However, the mechanism underlying the effect of melatonin on adipogenesis is still unknown.

OBJECTIVE:

To determine whether melatonin can inhibit the adipogenesis of bone marrow mesenchymal stem cells through retinoid-related orphan receptor α.

METHODS:

Bone marrow mesenchymal stem cells were isolated and purified by density gradient centrifugation combined with cell attachment culture. The phenotype was investigated by flow cytometry. Then, cells were induced for adipogenic differentiation with melatonin, CGP52608 and normal adipose tissue, respectively. The levels of retinoid-related orphan receptor α mRNA and protein were investigated by real-time RT-PCR and western blot assay, respectively. Further, the effect of retinoid-related orphan receptor α on the dipogenic differentiation of bone marrow mesenchymal stem cells was investigated by CGP52608.

RESULTS AND CONCLUSION:

The primary isolated bone marrow mesenchymal stem cells were spindle-shaped fibroblast-like cells. These cells did not express hematopoietic stem cells markers: CD34 and CD45; and highly expressed MSC markers: CD29, CD44, and CD10. The result of RT-PCR demonstrated that melatonin nuclear receptor, retinoid-related orphan receptor α, was highly expressed in bone marrow mesenchymal stem cells and the expression of retinoid-related orphan receptor α was further enhanced by melatonin in a dose-dependent manner, which was confirmed at protein level by western blot assay. During adiogenesis, the expression of retinoid-related orphan receptor α mRNA was up-regulated in the early stage, but maintained at a low level in the mild-later stage. While the retinoid-related orphan receptor α was activated by agonist CGP52608, the adipogenic differentiation of bone marrow mesenchymal stem cells was inhibited, which was similar to the inhibitory effect of melatonin. Therefore, melatonin inhibited the adipogenic differentiation of bone marrow mesenchymal stem cells through retinoid-related orphan receptor α, suggesting that melatonin plays an important role in the differentiation of adipocytes.

Funding:

the National Natural Science Foundation of China, No. 81301524, 81171674; the Natural Science Foundation of Guangdong Province, No. S2013040015484; the Specialized Research Fund for the Doctoral Program of Higher Education, No. 20110171110067

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