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The Effect of α MSH Analogues on Rat Bones

 Sung Kil Lim  ;  Song Zhe Li  ;  Yumie Rhee  ;  Sang Su Chung  ;  Yong Jun Jin  ;  Jong In Yook 
 YONSEI MEDICAL JOURNAL, Vol.43(4) : 500-510, 2002 
Journal Title
Issue Date
Animals ; Body Weight/drug effects ; Bone and Bones/drug effects* ; CHO Cells ; Cricetinae ; Cyclic AMP/biosynthesis ; Eating/drug effects ; Male ; Osteoblasts/drug effects ; Osteoblasts/physiology ; Osteoclasts/drug effects ; Osteoclasts/physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Corticotropin/physiology ; Receptors, Melanocortin ; alpha-MSH/analogs & derivatives ; alpha-MSH/pharmacology*
α MSH ; bone mineral density ; osteoclast
Melanocortin is the downstream mediator of leptin signaling and absence of leptin signaling in ob/ob and db/db mice revealed the enhancement of bone formation through the central regulation. While α-melanocyte-stimulating hormone (α MSH) 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, 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 (346.0±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 BMD 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 was found after treatment of the α MSH analogues peripherally.
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2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Rhee, Yumie(이유미) ORCID logo https://orcid.org/0000-0003-4227-5638
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