Osteoblast-derived NOTUM reduces cortical bone mass in mice and the NOTUM locus is associated with bone mineral density in humans

Registro completo de metadados
Autor(es): dc.contributorUniversity of Gothenburg-
Autor(es): dc.contributorErasmus University Rotterdam-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniversity of Oulu-
Autor(es): dc.contributorUniversity of Ulm-
Autor(es): dc.contributorSorbonne Paris Cité-
Autor(es): dc.contributorEquipe Labellisée Ligue Nationale contre le Cancer-
Autor(es): dc.contributorUniversidade Federal de Goiás (UFG)-
Autor(es): dc.creatorMovérare-Skrtic, Sofia-
Autor(es): dc.creatorNilsson, Karin H.-
Autor(es): dc.creatorHenning, Petra-
Autor(es): dc.creatorFunck-Brentano, Thomas-
Autor(es): dc.creatorNethander, Maria-
Autor(es): dc.creatorRivadeneira, Fernando-
Autor(es): dc.creatorNunes, Glaucia Coletto [UNESP]-
Autor(es): dc.creatorKoskela, Antti-
Autor(es): dc.creatorTuukkanen, Juha-
Autor(es): dc.creatorTuckermann, Jan-
Autor(es): dc.creatorPerret, Christine-
Autor(es): dc.creatorSouza, Pedro Paulo Chaves [UNESP]-
Autor(es): dc.creatorLerner, Ulf H.-
Autor(es): dc.creatorOhlsson, Claes-
Data de aceite: dc.date.accessioned2022-02-22T00:23:10Z-
Data de disponibilização: dc.date.available2022-02-22T00:23:10Z-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2019-10-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1096/fj.201900707R-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/197966-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/197966-
Descrição: dc.descriptionOsteoporosis is a common skeletal disease, affecting millions of individuals worldwide. Currently used osteoporosis treatments substantially reduce vertebral fracture risk, whereas nonvertebral fracture risk, mainly caused by reduced cortical bone mass, has only moderately been improved by the osteoporosis drugs used, defining an unmet medical need. Because several wingless-type MMTV integration site family members (WNTs) and modulators of WNT activity are major regulators of bone mass, we hypothesized that NOTUM, a secreted WNT lipase, might modulate bone mass via an inhibition of WNT activity. To characterize the possible role of endogenous NOTUM as a physiologic modulator of bone mass, we developed global, cell-specific, and inducible Notum-inactivated mouse models. Notum expression was high in the cortical bone in mice, and conditional Notum inactivation revealed that osteoblast lineage cells are the principal source of NOTUM in the cortical bone. Osteoblast lineage–specific Notum inactivation increased cortical bone thickness via an increased periosteal circumference. Inducible Notum inactivation in adult mice increased cortical bone thickness as a result of increased periosteal bone formation, and silencing of Notum expression in cultured osteoblasts enhanced osteoblast differentiation. Large-scale human genetic analyses identified genetic variants mapping to the NOTUM locus that are strongly associated with bone mineral density (BMD) as estimated with quantitative ultrasound in the heel. Thus, osteoblast-derived NOTUM is an essential local physiologic regulator of cortical bone mass via effects on periosteal bone formation in adult mice, and genetic variants in the NOTUM locus are associated with BMD variation in adult humans. Therapies targeting osteoblast-derived NOTUM may prevent nonvertebral fractures.—Movérare-Skrtic, S., Nilsson, K. H., Henning, P., Funck-Brentano, T., Nethander, M., Rivadeneira, F., Coletto Nunes, G., Koskela, A., Tuukkanen, J., Tuckermann, J., Perret, C., Souza, P. P. C., Lerner, U. H., Ohlsson, C. Osteoblast-derived NOTUM reduces cortical bone mass in mice and the NOTUM locus is associated with bone mineral density in humans. FASEB J. 33, 11163–11179 (2019). www.fasebj.org.-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionDementia Collaborative Research Centres, Australia-
Descrição: dc.descriptionDeutsche Forschungsgemeinschaft-
Descrição: dc.descriptionNovo Nordisk Fonden-
Descrição: dc.descriptionStiftelsen för Strategisk Forskning-
Descrição: dc.descriptionVetenskapsrådet-
Descrição: dc.descriptionIngaBritt och Arne Lundbergs Forskningsstiftelse-
Descrição: dc.descriptionDepartment of Internal Medicine and Clinical Nutrition Institute of Medicine Centre for Bone and Arthritis Research at the Sahlgrenska Academy University of Gothenburg-
Descrição: dc.descriptionDepartment of Internal Medicine Erasmus University Rotterdam-
Descrição: dc.descriptionBone Biology Research Group School of Dentistry São Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Anatomy and Cell Biology Faculty of Medicine Institute of Cancer Research and Translational Medicine University of Oulu-
Descrição: dc.descriptionInstitute of General Zoology and Endocrinology University of Ulm-
Descrição: dc.descriptionINSERM Unité 1016 Institut Cochin Université Paris Descartes Sorbonne Paris Cité-
Descrição: dc.descriptionEquipe Labellisée Ligue Nationale contre le Cancer-
Descrição: dc.descriptionSchool of Dentistry Federal University of Goiás-
Descrição: dc.descriptionBone Biology Research Group School of Dentistry São Paulo State University (UNESP)-
Formato: dc.format11163-11179-
Idioma: dc.languageen-
Relação: dc.relationFASEB Journal-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectosteoporosis-
Palavras-chave: dc.subjecttransgenic-
Palavras-chave: dc.subjectWNT16-
Título: dc.titleOsteoblast-derived NOTUM reduces cortical bone mass in mice and the NOTUM locus is associated with bone mineral density in humans-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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