α-melanocyte stimulating hormone (α-MSH) promotes osteoblast differentiation of MC3T3-E1 cells

alpha-melanocyte stimulating hormone (alpha-MSH) is a member of the melanocortin family, that has displayed important biological functions in diverse cells and tissues. The purpose of this study is to test the effect of alpha-MSH on the differentiation and mineralization of osteoblast cells. The expression of the alpha-MSH membrane receptor MC1R but not MC2R, MC3R, or MC4R increased distinctively during the osteogenic differentiation from 3, 7 to 14 d. Treatment with alpha-MSH promoted the differentiation and mineralization of MC3T3-E1 cells by increasing the activity of ALP, enhancing Alizarin Red S staining, and stimulating the expression of osteogenic genes, including ALP1, osteocalcin (Bglap2), and osterix (Sp7). Importantly, we found that alpha-MSH increased the expression of Runx-2, a master transcriptional factor of osteogenic differentiation. Mechanically, we found that the activation of ERK1/2 was involved in this process. Using the small interfering (si) RNA knockdown experiment, we proved that the effects of alpha-MSH on differentiation and mineralization of osteoblast cells are mediated by MC1R. The present study proposes alpha-MSH as a potential therapeutic agent to stimulate bone formation for osteoporosis and bone defect. Meanwhile, MC1R could also be a target candidate for the treatment of bone metabolism diseases.