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Article: The forkhead transcription factor Foxc2 promotes osteoblastogenesis via up-regulation of integrin β1 expression

TitleThe forkhead transcription factor Foxc2 promotes osteoblastogenesis via up-regulation of integrin β1 expression
Authors
KeywordsBone anabolic agent
Forkhead-binding element
Foxc2
Integrin β1
Issue Date2011
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/bone
Citation
Bone, 2011, v. 49 n. 3, p. 428-438 How to Cite?
AbstractThe forkhead box C2 (Foxc2) protein, a member of the forkhead/winged helix transcription factor family, plays an important role in regulation of metabolism, arterial specification, and vascular sprouting. Foxc2-null mutants die prenatally or perinatally, and they exhibit hypoplasia of the vertebrae and insufficient chondrification or ossification of medial structures. However, the role of Foxc2 in osteoblastogenesis is not yet fully understood. According to the degree of differentiation of osteoblasts, we found that Foxc2 expression was gradually increased and dose-dependently up-regulated by well-known bone anabolic agents, such as hPTH(1-34) and BMP2. In ex vivo mouse calvarial organ culture, a significant reduction of the basal expression of Foxc2 induced by siFoxc2 remarkably suppressed cell proliferation and differentiation and induced cell death. Knockdown of Foxc2 expression using siFoxc2 in both MC3T3-E1 and primary mouse calvarial cells also resulted in a significant suppression of proliferation and differentiation, and induced cell death, supporting the ex vivo observations. In addition, the resistance to apoptosis induced by serum deprivation and phosphorylation of both Akt and ERK was significantly reduced after siFoxc2 treatment. Conversely, overexpression of Foxc2 increased the proliferation of MC3T3-E1 and primary mouse calvarial cells. Furthermore, we found that Foxc2 enhanced the expression of integrin β1, an important modulator of osteoblastogenesis, by direct binding to a Forkhead-binding element in its promoter. Taken together, these results indicate that Foxc2 plays an important role in osteoblastogenesis by promoting osteoblast proliferation, survival and differentiation through up-regulation of integrin β1 in response to stimuli which induce bone formation. © 2011 Elsevier Inc.
Persistent Identifierhttp://hdl.handle.net/10722/169582
ISSN
2023 Impact Factor: 3.5
2023 SCImago Journal Rankings: 1.179
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPark, SJen_US
dc.contributor.authorGadi, Jen_US
dc.contributor.authorCho, KWen_US
dc.contributor.authorKim, KJen_US
dc.contributor.authorKim, SHen_US
dc.contributor.authorJung, HSen_US
dc.contributor.authorLim, SKen_US
dc.date.accessioned2012-10-25T04:53:08Z-
dc.date.available2012-10-25T04:53:08Z-
dc.date.issued2011en_US
dc.identifier.citationBone, 2011, v. 49 n. 3, p. 428-438en_US
dc.identifier.issn8756-3282en_US
dc.identifier.urihttp://hdl.handle.net/10722/169582-
dc.description.abstractThe forkhead box C2 (Foxc2) protein, a member of the forkhead/winged helix transcription factor family, plays an important role in regulation of metabolism, arterial specification, and vascular sprouting. Foxc2-null mutants die prenatally or perinatally, and they exhibit hypoplasia of the vertebrae and insufficient chondrification or ossification of medial structures. However, the role of Foxc2 in osteoblastogenesis is not yet fully understood. According to the degree of differentiation of osteoblasts, we found that Foxc2 expression was gradually increased and dose-dependently up-regulated by well-known bone anabolic agents, such as hPTH(1-34) and BMP2. In ex vivo mouse calvarial organ culture, a significant reduction of the basal expression of Foxc2 induced by siFoxc2 remarkably suppressed cell proliferation and differentiation and induced cell death. Knockdown of Foxc2 expression using siFoxc2 in both MC3T3-E1 and primary mouse calvarial cells also resulted in a significant suppression of proliferation and differentiation, and induced cell death, supporting the ex vivo observations. In addition, the resistance to apoptosis induced by serum deprivation and phosphorylation of both Akt and ERK was significantly reduced after siFoxc2 treatment. Conversely, overexpression of Foxc2 increased the proliferation of MC3T3-E1 and primary mouse calvarial cells. Furthermore, we found that Foxc2 enhanced the expression of integrin β1, an important modulator of osteoblastogenesis, by direct binding to a Forkhead-binding element in its promoter. Taken together, these results indicate that Foxc2 plays an important role in osteoblastogenesis by promoting osteoblast proliferation, survival and differentiation through up-regulation of integrin β1 in response to stimuli which induce bone formation. © 2011 Elsevier Inc.en_US
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/boneen_US
dc.relation.ispartofBoneen_US
dc.subjectBone anabolic agent-
dc.subjectForkhead-binding element-
dc.subjectFoxc2-
dc.subjectIntegrin β1-
dc.subject.mesh3T3 Cellsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntigens, Cd29 - Genetics - Metabolismen_US
dc.subject.meshBone Morphogenetic Protein 2 - Pharmacologyen_US
dc.subject.meshCell Cycle - Physiologyen_US
dc.subject.meshCell Differentiation - Drug Effects - Physiologyen_US
dc.subject.meshCell Proliferationen_US
dc.subject.meshCell Survivalen_US
dc.subject.meshForkhead Transcription Factors - Genetics - Metabolismen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshHumansen_US
dc.subject.meshIntegrin Alpha5 - Genetics - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshOsteoblasts - Cytology - Drug Effects - Physiologyen_US
dc.subject.meshParathyroid Hormone - Pharmacologyen_US
dc.subject.meshPeptide Fragments - Pharmacologyen_US
dc.subject.meshRna, Small Interfering - Genetics - Metabolismen_US
dc.subject.meshSkull - Cytology - Drug Effects - Physiologyen_US
dc.subject.meshTissue Culture Techniquesen_US
dc.subject.meshUp-Regulationen_US
dc.titleThe forkhead transcription factor Foxc2 promotes osteoblastogenesis via up-regulation of integrin β1 expressionen_US
dc.typeArticleen_US
dc.identifier.emailJung, HS: hsjung@yuhs.acen_US
dc.identifier.authorityJung, HS=rp01683en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.bone.2011.05.012en_US
dc.identifier.pmid21640215-
dc.identifier.scopuseid_2-s2.0-79960575675en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79960575675&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume49en_US
dc.identifier.issue3en_US
dc.identifier.spage428en_US
dc.identifier.epage438en_US
dc.identifier.isiWOS:000293805100014-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridPark, SJ=35285960200en_US
dc.identifier.scopusauthoridGadi, J=25222682000en_US
dc.identifier.scopusauthoridCho, KW=7403956665en_US
dc.identifier.scopusauthoridKim, KJ=36494695700en_US
dc.identifier.scopusauthoridKim, SH=34769729600en_US
dc.identifier.scopusauthoridJung, HS=7403030195en_US
dc.identifier.scopusauthoridLim, SK=7404080753en_US
dc.identifier.citeulike9377083-
dc.identifier.issnl1873-2763-

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