Genetic analysis of osteoblast activity identifies Zbtb40 as a regulator of osteoblast activity and bone mass.

Osteoporosis is a genetic disease characterized by progressive reductions in bone mineral density (BMD) leading to an increased risk of fracture. Over the last decade, genome-wide association studies (GWASs) have identified over 1000 associations for BMD. However, as a phenotype BMD is challenging a...

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Autores principales:	Madison L Doolittle, Gina M Calabrese, Larry D Mesner, Dana A Godfrey, Robert D Maynard, Cheryl L Ackert-Bicknell, Charles R Farber
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/ba9084e0cc5e4ca1b66b6852a2ebf052
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spelling	oai:doaj.org-article:ba9084e0cc5e4ca1b66b6852a2ebf0522021-12-02T20:02:47ZGenetic analysis of osteoblast activity identifies Zbtb40 as a regulator of osteoblast activity and bone mass.1553-73901553-740410.1371/journal.pgen.1008805https://doaj.org/article/ba9084e0cc5e4ca1b66b6852a2ebf0522020-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1008805https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Osteoporosis is a genetic disease characterized by progressive reductions in bone mineral density (BMD) leading to an increased risk of fracture. Over the last decade, genome-wide association studies (GWASs) have identified over 1000 associations for BMD. However, as a phenotype BMD is challenging as bone is a multicellular tissue affected by both local and systemic physiology. Here, we focused on a single component of BMD, osteoblast-mediated bone formation in mice, and identified associations influencing osteoblast activity on mouse Chromosomes (Chrs) 1, 4, and 17. The locus on Chr. 4 was in an intergenic region between Wnt4 and Zbtb40, homologous to a locus for BMD in humans. We tested both Wnt4 and Zbtb40 for a role in osteoblast activity and BMD. Knockdown of Zbtb40, but not Wnt4, in osteoblasts drastically reduced mineralization. Additionally, loss-of-function mouse models for both genes exhibited reduced BMD. Our results highlight that investigating the genetic basis of in vitro osteoblast mineralization can be used to identify genes impacting bone formation and BMD.Madison L DoolittleGina M CalabreseLarry D MesnerDana A GodfreyRobert D MaynardCheryl L Ackert-BicknellCharles R FarberPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 16, Iss 6, p e1008805 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Madison L Doolittle Gina M Calabrese Larry D Mesner Dana A Godfrey Robert D Maynard Cheryl L Ackert-Bicknell Charles R Farber Genetic analysis of osteoblast activity identifies Zbtb40 as a regulator of osteoblast activity and bone mass.
description	Osteoporosis is a genetic disease characterized by progressive reductions in bone mineral density (BMD) leading to an increased risk of fracture. Over the last decade, genome-wide association studies (GWASs) have identified over 1000 associations for BMD. However, as a phenotype BMD is challenging as bone is a multicellular tissue affected by both local and systemic physiology. Here, we focused on a single component of BMD, osteoblast-mediated bone formation in mice, and identified associations influencing osteoblast activity on mouse Chromosomes (Chrs) 1, 4, and 17. The locus on Chr. 4 was in an intergenic region between Wnt4 and Zbtb40, homologous to a locus for BMD in humans. We tested both Wnt4 and Zbtb40 for a role in osteoblast activity and BMD. Knockdown of Zbtb40, but not Wnt4, in osteoblasts drastically reduced mineralization. Additionally, loss-of-function mouse models for both genes exhibited reduced BMD. Our results highlight that investigating the genetic basis of in vitro osteoblast mineralization can be used to identify genes impacting bone formation and BMD.
format	article
author	Madison L Doolittle Gina M Calabrese Larry D Mesner Dana A Godfrey Robert D Maynard Cheryl L Ackert-Bicknell Charles R Farber
author_facet	Madison L Doolittle Gina M Calabrese Larry D Mesner Dana A Godfrey Robert D Maynard Cheryl L Ackert-Bicknell Charles R Farber
author_sort	Madison L Doolittle
title	Genetic analysis of osteoblast activity identifies Zbtb40 as a regulator of osteoblast activity and bone mass.
title_short	Genetic analysis of osteoblast activity identifies Zbtb40 as a regulator of osteoblast activity and bone mass.
title_full	Genetic analysis of osteoblast activity identifies Zbtb40 as a regulator of osteoblast activity and bone mass.
title_fullStr	Genetic analysis of osteoblast activity identifies Zbtb40 as a regulator of osteoblast activity and bone mass.
title_full_unstemmed	Genetic analysis of osteoblast activity identifies Zbtb40 as a regulator of osteoblast activity and bone mass.
title_sort	genetic analysis of osteoblast activity identifies zbtb40 as a regulator of osteoblast activity and bone mass.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/ba9084e0cc5e4ca1b66b6852a2ebf052
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Genetic analysis of osteoblast activity identifies Zbtb40 as a regulator of osteoblast activity and bone mass.

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