Cited 106 times in
The ERK MAPK Pathway Is Essential for Skeletal Development and Homeostasis
DC Field | Value | Language |
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dc.contributor.author | 박광환 | - |
dc.date.accessioned | 2020-06-04T08:39:47Z | - |
dc.date.available | 2020-06-04T08:39:47Z | - |
dc.date.issued | 2019-04 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/175834 | - |
dc.description.abstract | Mitogen-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.statementOfResponsibility | open | - |
dc.language | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.publisher | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.relation.isPartOf | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Biomarkers | - |
dc.subject.MESH | Bone Development* / genetics | - |
dc.subject.MESH | Bone and Bones / metabolism | - |
dc.subject.MESH | Bone and Bones / pathology | - |
dc.subject.MESH | Cell Differentiation | - |
dc.subject.MESH | Cleidocranial Dysplasia / genetics | - |
dc.subject.MESH | Cleidocranial Dysplasia / metabolism | - |
dc.subject.MESH | Cleidocranial Dysplasia / pathology | - |
dc.subject.MESH | Disease Models, Animal | - |
dc.subject.MESH | Disease Susceptibility | - |
dc.subject.MESH | Extracellular Signal-Regulated MAP Kinases / metabolism* | - |
dc.subject.MESH | Homeostasis* | - |
dc.subject.MESH | Immunohistochemistry | - |
dc.subject.MESH | MAP Kinase Signaling System* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Knockout | - |
dc.subject.MESH | Osteoblasts / cytology | - |
dc.subject.MESH | Osteoblasts / metabolism | - |
dc.subject.MESH | Osteogenesis / genetics | - |
dc.title | The ERK MAPK Pathway Is Essential for Skeletal Development and Homeostasis | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Orthopedic Surgery (정형외과학교실) | - |
dc.contributor.googleauthor | Jung-Min Kim | - |
dc.contributor.googleauthor | Yeon-Suk Yang | - |
dc.contributor.googleauthor | Kwang Hwan Park | - |
dc.contributor.googleauthor | Hwanhee Oh | - |
dc.contributor.googleauthor | Matthew B Greenblatt | - |
dc.contributor.googleauthor | Jae-Hyuck Shim | - |
dc.identifier.doi | 10.3390/ijms20081803 | - |
dc.contributor.localId | A01437 | - |
dc.relation.journalcode | J01133 | - |
dc.identifier.eissn | 1422-0067 | - |
dc.identifier.pmid | 31013682 | - |
dc.subject.keyword | ERK | - |
dc.subject.keyword | MAPK | - |
dc.subject.keyword | MEK1 | - |
dc.subject.keyword | MEK2 | - |
dc.subject.keyword | cleidocranial dysplasia | - |
dc.subject.keyword | osteoblast | - |
dc.subject.keyword | osteopenia | - |
dc.contributor.alternativeName | Park, Kwang Hwan | - |
dc.contributor.affiliatedAuthor | 박광환 | - |
dc.citation.volume | 20 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | e1803 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.20(8) : e1803, 2019-04 | - |
dc.identifier.rimsid | 64415 | - |
dc.type.rims | ART | - |
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