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A Novel Human PTH Analog [Cys25]hPTH(1-34) Restores Bone Mass in Ovariectomized Mice
DC Field | Value | Language |
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dc.contributor.author | 강명모 | - |
dc.contributor.author | 신동민 | - |
dc.contributor.author | 임승길 | - |
dc.date.accessioned | 2017-10-26T07:43:25Z | - |
dc.date.available | 2017-10-26T07:43:25Z | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 0021-972X | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/152426 | - |
dc.description.abstract | CONTEXT: Recently, an arginine-to-cysteine homozygous mutation at position 25 in mature PTH was reported in a Korean patient with hypoparathyroidism. OBJECTIVE: To clarify whether the high bone mass phenotype observed in this patient was related to the hypoparathyroidism itself or to chronic elevation of mutant PTH. METHODS: A series of in vitro and in vivo experiments were performed in MC3T3E1, ROS 17/2.8, and SAOS2 cells treated with human (h)PTH(1-34), Cys25hPTH(1-34), Ala1Cys25hPTH(1-34), and Bpa1Cys25hPTH(1-34). The peptides were then sc delivered to ovariectomized mice as daily single injections. RESULTS: Compared with hPTH(1-34) and Ala1Cys25hPTH(1-34), treatment with Cys25hPTH(1-34) or Bpa1Cys25hPTH(1-34) resulted in decreases in the cAMP response and promoter-cAMP-response element luciferase reporter activity. Although the cAMP response was sustained with hPTH(1-34) in MC3T3E1 cells, such response was not observed with the other mutated peptides. Meanwhile, all PTH analogues exhibited ERK phosphorylation and cytoplasmic Ca++ signals comparable with hPTH(1-34). On microcomputed tomography analyses, trabecular and cortical bone parameters improved after 6 weeks of respective treatments as follows: hPTH(1-34) (80 μg/kg) = Ala1Cys25hPTH(1-34) (80 μg/kg) = Cys25hPTH(1-34) (80 μg/kg) > Bpa1Cys25hPTH(1-34) (80 μg/kg) > hPTH(1-34) (40 μg/kg). The increment of RANKL to OPG mRNA ratio in the MC3T3E1 cells after 6 hours of treatment of Cys25hPTH(1-34), AL1Cys25hPTH(1-34), and Bpa1Cys25hPTH(1-34) was less than that was obtained after hPTH(1-34) treatment. On bone histomorphometric analysis, AL1Cys25hPTH(1-34) increased the bone formation rate in both trabecular and periosteal bones compared with the control group. CONCLUSION: The high bone mass phenotype observed in this patient with hypoparathyrodism caused by a Cys mutation at the 25th residue of hPTH(1-84) may have arisen from both direct and indirect effects exerted by the mutant PTH itself on bone. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Endocrine Society | - |
dc.relation.isPartOf | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Bone Density/drug effects* | - |
dc.subject.MESH | Cell Culture Techniques | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | Ovariectomy | - |
dc.subject.MESH | Parathyroid Hormone/analysis | - |
dc.subject.MESH | Parathyroid Hormone/genetics | - |
dc.subject.MESH | Parathyroid Hormone/pharmacology* | - |
dc.subject.MESH | Signal Transduction/drug effects* | - |
dc.title | A Novel Human PTH Analog [Cys25]hPTH(1-34) Restores Bone Mass in Ovariectomized Mice | - |
dc.type | Article | - |
dc.publisher.location | United States | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Life Science | - |
dc.contributor.googleauthor | Chu Hyun Bae | - |
dc.contributor.googleauthor | Myeongmo Kang | - |
dc.contributor.googleauthor | Clara Yongjoo Park | - |
dc.contributor.googleauthor | Bo Mi Park | - |
dc.contributor.googleauthor | Dongdong Zhang | - |
dc.contributor.googleauthor | Hee Jin Nam | - |
dc.contributor.googleauthor | Yu-Mi Yang | - |
dc.contributor.googleauthor | Dong Min Shin | - |
dc.contributor.googleauthor | Je-Yong Choi | - |
dc.contributor.googleauthor | Sung-Kil Lim | - |
dc.identifier.doi | 10.1210/jc.2016-1640 | - |
dc.contributor.localId | A02091 | - |
dc.contributor.localId | A03375 | - |
dc.contributor.localId | A04871 | - |
dc.relation.journalcode | J01318 | - |
dc.identifier.eissn | 1945-7197 | - |
dc.identifier.pmid | 27300576 | - |
dc.identifier.url | https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2016-1640 | - |
dc.contributor.alternativeName | Kang, Myengmo | - |
dc.contributor.alternativeName | Shin, Dong Min | - |
dc.contributor.alternativeName | Lim, Sung Kil | - |
dc.contributor.affiliatedAuthor | Shin, Dong Min | - |
dc.contributor.affiliatedAuthor | Lim, Sung Kil | - |
dc.contributor.affiliatedAuthor | Kang, Myengmo | - |
dc.citation.volume | 101 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 3700 | - |
dc.citation.endPage | 3708 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol.101(10) : 3700-3708, 2016 | - |
dc.date.modified | 2017-10-24 | - |
dc.identifier.rimsid | 48633 | - |
dc.type.rims | ART | - |
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