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Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption

Vav1 is a Rho/Rac guanine nucleotide exchange factor primarily expressed in hematopoietic cells. In this study, we investigated the potential role of Vav1 in osteoclast (OC) differentiation by comparing the ability of bone marrow mononuclear cells (BMMCs) obtained from Vav1-deficient (Vav1(−/−)) and...

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Autores principales: Jang, Jin Sun, Kang, In Soon, Cha, Young-Nam, Lee, Zang Hee, Dinauer, Mary C, Kim, Young-June, Kim, Chaekyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889896/
https://www.ncbi.nlm.nih.gov/pubmed/31072447
http://dx.doi.org/10.5483/BMBRep.2019.52.11.013
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author Jang, Jin Sun
Kang, In Soon
Cha, Young-Nam
Lee, Zang Hee
Dinauer, Mary C
Kim, Young-June
Kim, Chaekyun
author_facet Jang, Jin Sun
Kang, In Soon
Cha, Young-Nam
Lee, Zang Hee
Dinauer, Mary C
Kim, Young-June
Kim, Chaekyun
author_sort Jang, Jin Sun
collection PubMed
description Vav1 is a Rho/Rac guanine nucleotide exchange factor primarily expressed in hematopoietic cells. In this study, we investigated the potential role of Vav1 in osteoclast (OC) differentiation by comparing the ability of bone marrow mononuclear cells (BMMCs) obtained from Vav1-deficient (Vav1(−/−)) and wild-type (WT) mice to differentiate into mature OCs upon stimulation with macrophage colony stimulating factor and receptor activator of nuclear kappa B ligand in vitro. Our results suggested that Vav1 deficiency promoted the differentiation of BMMCs into OCs, as indicated by the increased expression of tartrate-resistant acid phosphatase, cathepsin K, and calcitonin receptor. Therefore, Vav1 may play a negative role in OC differentiation. This hypothesis was supported by the observation of more OCs in the femurs of Vav1(−/−) mice than in WT mice. Furthermore, the bone status of Vav1(−/−) mice was analyzed in situ and the femurs of Vav1(−/−) mice appeared abnormal, with poor bone density and fewer number of trabeculae. In addition, Vav1-deficient OCs showed stronger adhesion to vitronectin, an α(v)β(3) integrin ligand important in bone resorption. Thus, Vav1 may inhibit OC differentiation and protect against bone resorption.
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spelling pubmed-68898962019-12-10 Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption Jang, Jin Sun Kang, In Soon Cha, Young-Nam Lee, Zang Hee Dinauer, Mary C Kim, Young-June Kim, Chaekyun BMB Rep Articles Vav1 is a Rho/Rac guanine nucleotide exchange factor primarily expressed in hematopoietic cells. In this study, we investigated the potential role of Vav1 in osteoclast (OC) differentiation by comparing the ability of bone marrow mononuclear cells (BMMCs) obtained from Vav1-deficient (Vav1(−/−)) and wild-type (WT) mice to differentiate into mature OCs upon stimulation with macrophage colony stimulating factor and receptor activator of nuclear kappa B ligand in vitro. Our results suggested that Vav1 deficiency promoted the differentiation of BMMCs into OCs, as indicated by the increased expression of tartrate-resistant acid phosphatase, cathepsin K, and calcitonin receptor. Therefore, Vav1 may play a negative role in OC differentiation. This hypothesis was supported by the observation of more OCs in the femurs of Vav1(−/−) mice than in WT mice. Furthermore, the bone status of Vav1(−/−) mice was analyzed in situ and the femurs of Vav1(−/−) mice appeared abnormal, with poor bone density and fewer number of trabeculae. In addition, Vav1-deficient OCs showed stronger adhesion to vitronectin, an α(v)β(3) integrin ligand important in bone resorption. Thus, Vav1 may inhibit OC differentiation and protect against bone resorption. Korean Society for Biochemistry and Molecular Biology 2019-11 2019-11-30 /pmc/articles/PMC6889896/ /pubmed/31072447 http://dx.doi.org/10.5483/BMBRep.2019.52.11.013 Text en Copyright © 2019 by the The Korean Society for Biochemistry and Molecular Biology This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Jang, Jin Sun
Kang, In Soon
Cha, Young-Nam
Lee, Zang Hee
Dinauer, Mary C
Kim, Young-June
Kim, Chaekyun
Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption
title Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption
title_full Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption
title_fullStr Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption
title_full_unstemmed Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption
title_short Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption
title_sort vav1 inhibits rankl-induced osteoclast differentiation and bone resorption
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889896/
https://www.ncbi.nlm.nih.gov/pubmed/31072447
http://dx.doi.org/10.5483/BMBRep.2019.52.11.013
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