Melanocortin is the downstream mediator of leptin signaling absence of leptin signaling in ob/ob and db/db mice revealed the enhancement of bone formation through the central regulation. While alpha-melanocyte-stimulating hormone (α NISH) inhibits the secretion of interleukin-1 α and tumor necrosis factor- α from the inflammatory cells, α MSH can also enhance clonal expansion of pro B cells linked to stimulation of osteoclastogenesis. Therefore, we tested the effect of melanocortin on bones. α MSH analogues [6His] α MSH-ND and [6Asn] α MSH-ND were synthesized and the radio-ligand receptor binding- and cyclic AMP generating activity were analyzed in China Hamster Ovary cell line over- expressing melanocortin receptors. The EC50 of [6His] α MSH-ND measured from melanocortin-1, 3, 4 and 5 receptors were 0.008 ± 0.0045, 1.523 ± 0.707, 0.780 ± 0.405, 6 and 250.320 ± 42.234 nM, respectively, and the EC50 of [6Asn] α MSH-ND were 16.8 ± 6.94, 271.8 ± 21.95, 8.0 ± 1.21, and 1132.5 ± 635.46 nM, respectively. Four weeks after the subcutaneous injection of the analogues, the body weights in the [6His] α MSH-ND and the [6Asn] α MSH-ND treated groups (346.6 ± 20.63 g vs. 350.0 ± 13.57 g) were lower than that of the vehicle treated group (375.8 ± 17.31 g, p < 0.05). There was no difference in the total femoral BNM measured by dual x-ray absorptiometry among the three groups. Among the three groups, there were no differences in the total numbers of crystal violet positive- or alkaline phosphatase positive colonies, in the expression of Receptor Activator of Nuclear Factor Kappa-B ligand on the tibia and the total number of multinucleated osteoclast-like cells differentiated from primary cultured bone marrow cells. From the above results, no evidence of bone gain or loss found after treatment of the α MSH analogues peripherally.
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