Gsalpha mutation and increased production of cAMP and IL-6 in patients with McCune-Albright syndrome.
| Project/Area Number |
08670884
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
SHIMA Masaaki (1997) Osaka University Medical School, Assistant Professor, 医学部, 助手 (10252660)
山本 威久 (1996) 大阪大学, 医学部, 助手 (30231674)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Sayuri Osaka University Medical School, Assistant Professor, 医学部, 助手 (10281122)
OZONO Keiichi Osaka Med.Center for Matern.and Child Health, Director, 環境影響部門, 部長 (20270770)
島 雅昭 大阪大学, 医学部, 助手 (10252660)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | McCune-Albright syndrome / Gsalpha mutation / cyclic AMP / IL-6 / fibrous dysplasia / Gsα protein / osteoclast / Pagets disease |
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| Research Abstract |
McCune-Albright syndrome (MAS) is characterized by cafe-au-lait spot, multiple endocrine hyperfunction and polyostotic fibrous dysplasia. A somatic point mutation of G_Salpha protein was reported to decrease GTPase activity, leading to increase in the G_Salpha-associated hormone actions via cyclic AMP.IL-6 is known to stimulate osteoclast formation, in which promoter a cyclic AMP responsive element has been identified. In this paper, we investigated the role of IL-6 in the bone lesions of MAS,using the isolated fibrous cells from the polyostotic fibrous dysplasia tissues in bones of the two patients with MAS.Bone biopsy specimen revealed the increased osteoclast in number. In both patients, a G_Salpha mutation (Arg^<201>*His) was identified in the cultured fibrous cells. Intracellular cyclic AMP content and IL-6 secretion by the patient cells were increased. Rp-8Br-cAMP significantly inhibited IL-6 production in the patient cells, while it had no effects on normal control. The addition of dibutyryl cyclic AMP significantly increased the synthesis of IL-6 in normal control cells. In contrast, no effect of dibutyryl cyclic AMP on IL-6 synthesis was observed in the cells from one of the MAS patients. These data suggest that IL-6 is, at least, one of the downstream effectors of cyclic AMP and that the increased IL-6 synthesis has a pathogenic role in the bone lesions of MAS patients via increasing the number of osteoclasts. These results may provide new strategy for the therapy of MAS patients.
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Report
(3 results)
Research Products
(6 results)
