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Age-Progressive and Gender-Dependent Bone Phenotype in Mice Lacking Both Ebf1 and Ebf2 in Prrx1-Expressing Mesenchymal Cells

Nieminen-Pihala Vappu; Kiviranta Riku; Wang Fan; Tarkkonen Kati; Ivaska Kaisa K; Rummukainen Petri

dc.contributor.authorNieminen-Pihala Vappu
dc.contributor.authorKiviranta Riku
dc.contributor.authorWang Fan
dc.contributor.authorTarkkonen Kati
dc.contributor.authorIvaska Kaisa K
dc.contributor.authorRummukainen Petri
dc.date.accessioned2022-10-27T11:55:24Z
dc.date.available2022-10-27T11:55:24Z
dc.identifier.urihttps://www.utupub.fi/handle/10024/155932
dc.description.abstractEbfs are a family of transcription factors regulating the differentiation of multiple cell types of mesenchymal origin, including osteoblasts. Global deletion of Ebf1 results in increased bone formation and bone mass, while global loss of Ebf2 leads to enhanced bone resorption and decreased bone mass. Targeted deletion of Ebf1 in early committed osteoblasts leads to increased bone formation, whereas deletion in mature osteoblasts has no effect. To study the effects of Ebf2 specifically on long bone development, we created a limb bud mesenchyme targeted Ebf2 knockout mouse model by using paired related homeobox gene 1 (Prrx1) Cre. To investigate the possible interplay between Ebf1 and Ebf2, we deleted both Ebf1 and Ebf2 in the cells expressing Prrx1. Mice with Prrx1-targeted deletion of Ebf2 had a very mild bone phenotype. However, deletion of both Ebf1 and Ebf2 in mesenchymal lineage cells lead to significant, age progressive increase in bone volume. The phenotype was to some extent gender dependent, leading to an increase in both trabecular and cortical bone in females, while in males a mild cortical bone phenotype and a growth plate defect was observed. The phenotype was observed at both 6 and 12 weeks of age, but it was more pronounced in older female mice. Our data suggest that Ebfs modulate bone homeostasis and they are likely able to compensate for the lack of each other. The roles of Ebfs in bone formation appear to be complex and affected by multiple factors, such as age and gender.
dc.language.isoen
dc.publisherSPRINGER
dc.titleAge-Progressive and Gender-Dependent Bone Phenotype in Mice Lacking Both Ebf1 and Ebf2 in Prrx1-Expressing Mesenchymal Cells
dc.identifier.urnURN:NBN:fi-fe2022081153750
dc.relation.volume110
dc.contributor.organizationfi=tyks, vsshp|en=tyks, vsshp|
dc.contributor.organizationfi=biolääketieteen laitos, yhteiset|en=Institute of Biomedicine|
dc.contributor.organization-code2607100
dc.converis.publication-id174492267
dc.converis.urlhttps://research.utu.fi/converis/portal/Publication/174492267
dc.format.pagerange758
dc.format.pagerange746
dc.identifier.jour-issn0171-967X
dc.okm.affiliatedauthorTarkkonen, Kati
dc.okm.affiliatedauthorDataimport, tyks, vsshp
dc.okm.affiliatedauthorIvaska-Papaioannou, Kaisa
dc.okm.affiliatedauthorWang, Fan
dc.okm.affiliatedauthorRummukainen, Petri
dc.okm.affiliatedauthorKiviranta, Riku
dc.okm.affiliatedauthorNieminen-Pihala, Vappu
dc.okm.discipline3111 Biomedicineen_GB
dc.okm.discipline3111 Biolääketieteetfi_FI
dc.okm.internationalcopublicationnot an international co-publication
dc.okm.internationalityInternational publication
dc.okm.typeJournal article
dc.publisher.countryUnited Statesen_GB
dc.publisher.countryYhdysvallat (USA)fi_FI
dc.publisher.country-codeUS
dc.relation.doi10.1007/s00223-022-00951-7
dc.relation.ispartofjournalCalcified Tissue International
dc.year.issued2022


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