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The ERK MAPK Pathway Is Essential for Skeletal Development and Homeostasis

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dc.contributor.author박광환-
dc.date.accessioned2020-06-04T08:39:47Z-
dc.date.available2020-06-04T08:39:47Z-
dc.date.issued2019-04-
dc.identifier.issn1661-6596-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/175834-
dc.description.abstractMitogen-activated protein kinases (MAPKs) are a family of protein kinases that function as key signal transducers of a wide spectrum of extracellular stimuli, including growth factors and pro-inflammatory cytokines. Dysregulation of the extracellular signal-regulated kinase (ERK) MAPK pathway is associated with human skeletal abnormalities including Noonan syndrome, neurofibromatosis type 1, and cardiofaciocutaneous syndrome. Here, we demonstrate that ERK activation in osteoprogenitors is required for bone formation during skeletal development and homeostasis. Deletion of Mek1 and Mek2, kinases upstream of ERK MAPK, in osteoprogenitors (Mek1OsxMek2-/-), resulted in severe osteopenia and cleidocranial dysplasia (CCD), similar to that seen in humans and mice with impaired RUNX2 function. Additionally, tamoxifen-induced deletion of Mek1 and Mek2 in osteoprogenitors in adult mice (Mek1Osx-ERTMek2-/-) significantly reduced bone mass. Mechanistically, this corresponded to decreased activation of osteoblast master regulators, including RUNX2, ATF4, and β-catenin. Finally, we identified potential regulators of osteoblast differentiation in the ERK MAPK pathway using unbiased phospho-mass spectrometry. These observations demonstrate essential roles of ERK activation in osteogenesis and bone formation.-
dc.description.statementOfResponsibilityopen-
dc.languageINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.publisherINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.relation.isPartOfINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHBiomarkers-
dc.subject.MESHBone Development* / genetics-
dc.subject.MESHBone and Bones / metabolism-
dc.subject.MESHBone and Bones / pathology-
dc.subject.MESHCell Differentiation-
dc.subject.MESHCleidocranial Dysplasia / genetics-
dc.subject.MESHCleidocranial Dysplasia / metabolism-
dc.subject.MESHCleidocranial Dysplasia / pathology-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHDisease Susceptibility-
dc.subject.MESHExtracellular Signal-Regulated MAP Kinases / metabolism*-
dc.subject.MESHHomeostasis*-
dc.subject.MESHImmunohistochemistry-
dc.subject.MESHMAP Kinase Signaling System*-
dc.subject.MESHMice-
dc.subject.MESHMice, Knockout-
dc.subject.MESHOsteoblasts / cytology-
dc.subject.MESHOsteoblasts / metabolism-
dc.subject.MESHOsteogenesis / genetics-
dc.titleThe ERK MAPK Pathway Is Essential for Skeletal Development and Homeostasis-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Orthopedic Surgery (정형외과학교실)-
dc.contributor.googleauthorJung-Min Kim-
dc.contributor.googleauthorYeon-Suk Yang-
dc.contributor.googleauthorKwang Hwan Park-
dc.contributor.googleauthorHwanhee Oh-
dc.contributor.googleauthorMatthew B Greenblatt-
dc.contributor.googleauthorJae-Hyuck Shim-
dc.identifier.doi10.3390/ijms20081803-
dc.contributor.localIdA01437-
dc.relation.journalcodeJ01133-
dc.identifier.eissn1422-0067-
dc.identifier.pmid31013682-
dc.subject.keywordERK-
dc.subject.keywordMAPK-
dc.subject.keywordMEK1-
dc.subject.keywordMEK2-
dc.subject.keywordcleidocranial dysplasia-
dc.subject.keywordosteoblast-
dc.subject.keywordosteopenia-
dc.contributor.alternativeNamePark, Kwang Hwan-
dc.contributor.affiliatedAuthor박광환-
dc.citation.volume20-
dc.citation.number8-
dc.citation.startPagee1803-
dc.identifier.bibliographicCitationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.20(8) : e1803, 2019-04-
dc.identifier.rimsid64415-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers

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