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Nox4 expression in osteo-progenitors controls bone development in mice during early life

Tightly regulated and cell-specific NADPH-oxidases (Nox) represent one of the major sources of reactive oxygen species (ROS) signaling molecules that are involved in tissue development and stem cell self-renewal. We have characterized the role of Nox4 in osteo-progenitors during postnatal bone devel...

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Autores principales: Chen, Jin-Ran, Lazarenko, Oxana P., Blackburn, Michael L., Chen, Jennifer F., Randolph, Christopher E., Zabaleta, Jovanny, Schroder, Katrin, Pedersen, Kim B., Ronis, Martin J. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198054/
https://www.ncbi.nlm.nih.gov/pubmed/35701603
http://dx.doi.org/10.1038/s42003-022-03544-0
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author Chen, Jin-Ran
Lazarenko, Oxana P.
Blackburn, Michael L.
Chen, Jennifer F.
Randolph, Christopher E.
Zabaleta, Jovanny
Schroder, Katrin
Pedersen, Kim B.
Ronis, Martin J. J.
author_facet Chen, Jin-Ran
Lazarenko, Oxana P.
Blackburn, Michael L.
Chen, Jennifer F.
Randolph, Christopher E.
Zabaleta, Jovanny
Schroder, Katrin
Pedersen, Kim B.
Ronis, Martin J. J.
author_sort Chen, Jin-Ran
collection PubMed
description Tightly regulated and cell-specific NADPH-oxidases (Nox) represent one of the major sources of reactive oxygen species (ROS) signaling molecules that are involved in tissue development and stem cell self-renewal. We have characterized the role of Nox4 in osteo-progenitors during postnatal bone development. Nox4 expression in bone and ROS generation were increased during early osteoblast differentiation and bone development. Stromal osteoblastic cell self-renewal, proliferation and ROS production were significantly lower in samples from whole-body Nox4 knockout mice (Nox4(-/-)) and conditional knockout (CKO) mice with depletion of Nox4 in the limb bud mesenchyme compared with those from control mice (Nox4(fl/fl)), but they were reversed after 9 passages. In both sexes, bone volume, trabecular number and bone mineral density were significantly lower in 3-week old CKO and Nox4(-/-) mice compared with Nox4(fl/fl) controls. This was reflected in serum levels of bone formation markers alkaline phosphatase (ALP) and procollagen 1 intact N-terminal propeptide (P1NP). However, under-developed bone formation in 3-week old CKO and Nox4(-/-) mice quickly caught up to levels of control mice by 6-week of age, remained no different at 13-week of age, and was reversed in 32-week old male mice. Osteoclastogenesis showed no differences among groups, however, CTX1 reflecting osteoclast activity was significantly higher in 3-week old male CKO and Nox4(-/-) mice compared with control mice, and significantly lower in 32-week old Nox4(-/-) mice compared with control mice. These data suggest that Nox4 expression and ROS signaling in bone and osteoblastic cells coordinately play an important role in osteoblast differentiation, proliferation and maturation.
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spelling pubmed-91980542022-06-16 Nox4 expression in osteo-progenitors controls bone development in mice during early life Chen, Jin-Ran Lazarenko, Oxana P. Blackburn, Michael L. Chen, Jennifer F. Randolph, Christopher E. Zabaleta, Jovanny Schroder, Katrin Pedersen, Kim B. Ronis, Martin J. J. Commun Biol Article Tightly regulated and cell-specific NADPH-oxidases (Nox) represent one of the major sources of reactive oxygen species (ROS) signaling molecules that are involved in tissue development and stem cell self-renewal. We have characterized the role of Nox4 in osteo-progenitors during postnatal bone development. Nox4 expression in bone and ROS generation were increased during early osteoblast differentiation and bone development. Stromal osteoblastic cell self-renewal, proliferation and ROS production were significantly lower in samples from whole-body Nox4 knockout mice (Nox4(-/-)) and conditional knockout (CKO) mice with depletion of Nox4 in the limb bud mesenchyme compared with those from control mice (Nox4(fl/fl)), but they were reversed after 9 passages. In both sexes, bone volume, trabecular number and bone mineral density were significantly lower in 3-week old CKO and Nox4(-/-) mice compared with Nox4(fl/fl) controls. This was reflected in serum levels of bone formation markers alkaline phosphatase (ALP) and procollagen 1 intact N-terminal propeptide (P1NP). However, under-developed bone formation in 3-week old CKO and Nox4(-/-) mice quickly caught up to levels of control mice by 6-week of age, remained no different at 13-week of age, and was reversed in 32-week old male mice. Osteoclastogenesis showed no differences among groups, however, CTX1 reflecting osteoclast activity was significantly higher in 3-week old male CKO and Nox4(-/-) mice compared with control mice, and significantly lower in 32-week old Nox4(-/-) mice compared with control mice. These data suggest that Nox4 expression and ROS signaling in bone and osteoblastic cells coordinately play an important role in osteoblast differentiation, proliferation and maturation. Nature Publishing Group UK 2022-06-14 /pmc/articles/PMC9198054/ /pubmed/35701603 http://dx.doi.org/10.1038/s42003-022-03544-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chen, Jin-Ran
Lazarenko, Oxana P.
Blackburn, Michael L.
Chen, Jennifer F.
Randolph, Christopher E.
Zabaleta, Jovanny
Schroder, Katrin
Pedersen, Kim B.
Ronis, Martin J. J.
Nox4 expression in osteo-progenitors controls bone development in mice during early life
title Nox4 expression in osteo-progenitors controls bone development in mice during early life
title_full Nox4 expression in osteo-progenitors controls bone development in mice during early life
title_fullStr Nox4 expression in osteo-progenitors controls bone development in mice during early life
title_full_unstemmed Nox4 expression in osteo-progenitors controls bone development in mice during early life
title_short Nox4 expression in osteo-progenitors controls bone development in mice during early life
title_sort nox4 expression in osteo-progenitors controls bone development in mice during early life
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198054/
https://www.ncbi.nlm.nih.gov/pubmed/35701603
http://dx.doi.org/10.1038/s42003-022-03544-0
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