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The in vitro and in vivo effects of [Cys25]hPTH(1-34) analogues
DC Field | Value | Language |
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dc.contributor.author | 배주현 | - |
dc.date.accessioned | 2017-07-11T16:10:21Z | - |
dc.date.available | 2017-07-11T16:10:21Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/149133 | - |
dc.description | Dept. of Medical Science/석사 | - |
dc.description.abstract | Recently, an arginine (Arg)-to-cysteine (Cys) homozygous mutation at position 25 (R25C) in mature parathyroid hormone (PTH; 1-84) was reported in a Korean patient with hypoparathyroidism. To clarify whether the high bone mass phenotype observed in this patient is related to the hypoparathyroidism itself or a chronic elevation of mutant PTH, a series of in vitro and in vivo experiments were performed in MC3T3E1, ROS 17/2.8 and SAOS2 cells treated with hPTH(1-34), Cys25hPTH(1-34), Ala1Cys25hPTH(1-34) and Bpa1Cys25hPTH(1-34). The synthesized peptides were then subcutaneously delivered to OVX mice as a daily single-dose regimen. Compared to hPTH(1-34) and Ala1Cys25hPTH(1-34), treatment with Cys25hPTH(1-34) or Bpa1Cys25hPTH(1-34) revealed a decreased cAMP response and pCRE luciferase reporter activity. Although cAMP response was sustained with hPTH(1-34) in MC3T3E1 cells, such response was not observed when cells were treated with the three mutated peptides. Meanwhile, all PTH analogues exhibited ERK phosphorylation and cytoplasmic Ca++ signals comparable to hPTH(1-34). Compared to the control OVX mice, trabecular and cortical bone 2 parameters improved after 6 weeks of respective treatments as follows: hPTH(1-34)(80μg/kg) = Ala1Cys25hPTH(1-34)(80μg/kg) = Cys25hPTH(1-34)(80μg/kg) > Bpa1Cys25hPTH(1-34)(80μg/kg) > hPTH(1-34)(40μg/kg). The increment in RANKL/OPG mRNA ratio after 6 hr treatment of Cys25hPTH(1-34), Ala1Cys25hPTH(1-34) and Bpa1Cys25hPTH(1-34) was less than that was obtained after hPTH(1-34) treatment. In conclusion, the high bone mass phenotype observed in a Korean patient with hypoparathyrodism caused by an Arg to Cys mutation at the 25th residue of mature PTH(1-84), may arise from direct and indirect effects exerted by the mutant PTH itself on bone. Cys25PTH(1-34) could be a potential candidate as a second generation PTH | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.publisher | Graduate School, Yonsei University | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | The in vitro and in vivo effects of [Cys25]hPTH(1-34) analogues | - |
dc.title.alternative | [Cys25]hPTH(1-34) 유도체의 생체 내 및 생체 외 효과 | - |
dc.type | Thesis | - |
dc.contributor.alternativeName | Bae, Chu Hyun | - |
dc.type.local | Thesis | - |
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