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Stat3 in osteocytes mediates osteogenic response to loading
Signal transducer and activator of transcription 3 (Stat3) is a member of the Stat family of proteins involved in signaling in many different cell types, including osteocytes. Osteocytes are considered major mechanosensing cells in bone due to their intricate dendritic networks able to sense changes...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700265/ https://www.ncbi.nlm.nih.gov/pubmed/31440530 http://dx.doi.org/10.1016/j.bonr.2019.100218 |
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author | Corry, Kylie A. Zhou, Hongkang Brustovetsky, Tatiana Himes, Evan R. Bivi, Nicoletta Horn, M. Ryne Kitase, Yukiko Wallace, Joseph M. Bellido, Teresita Brustovetsky, Nickolay Li, Jiliang |
author_facet | Corry, Kylie A. Zhou, Hongkang Brustovetsky, Tatiana Himes, Evan R. Bivi, Nicoletta Horn, M. Ryne Kitase, Yukiko Wallace, Joseph M. Bellido, Teresita Brustovetsky, Nickolay Li, Jiliang |
author_sort | Corry, Kylie A. |
collection | PubMed |
description | Signal transducer and activator of transcription 3 (Stat3) is a member of the Stat family of proteins involved in signaling in many different cell types, including osteocytes. Osteocytes are considered major mechanosensing cells in bone due to their intricate dendritic networks able to sense changes in physical force and to orchestrate the response of osteoclasts and osteoblasts. We examined the role of Stat3 in osteocytes by generating mice lacking Stat3 in these cells using the Dmp-1(8kb)-Cre promoter (Stat3cKO mice). Compared to age-matched littermate controls, Stat3cKO mice of either sex (18 weeks old) exhibit reduced bone formation indices, decreased osteoblasts and increased osteoclasts, and altered material properties, without detectable changes in bone mineral density (BMD) or content of either trabecular or cortical bone. In addition, Stat3cKO mice of either sex show significantly decreased load-induced bone formation. Furthermore, pharmacologic inhibition of Stat3 in osteocytes in vitro with WP1066 blocked the increase in cytosolic calcium induced by ATP, a mediator of the cellular responses to sheer stress. WP1066 also increased reactive oxygen species (ROS) production in cultured MLO-Y4 osteocytes. These data demonstrate that Stat3 is a critical mediator of mechanical signals received by osteocytes and suggest that osteocytic Stat3 is a potential therapeutic target to stimulate bone anabolism. |
format | Online Article Text |
id | pubmed-6700265 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-67002652019-08-22 Stat3 in osteocytes mediates osteogenic response to loading Corry, Kylie A. Zhou, Hongkang Brustovetsky, Tatiana Himes, Evan R. Bivi, Nicoletta Horn, M. Ryne Kitase, Yukiko Wallace, Joseph M. Bellido, Teresita Brustovetsky, Nickolay Li, Jiliang Bone Rep Article Signal transducer and activator of transcription 3 (Stat3) is a member of the Stat family of proteins involved in signaling in many different cell types, including osteocytes. Osteocytes are considered major mechanosensing cells in bone due to their intricate dendritic networks able to sense changes in physical force and to orchestrate the response of osteoclasts and osteoblasts. We examined the role of Stat3 in osteocytes by generating mice lacking Stat3 in these cells using the Dmp-1(8kb)-Cre promoter (Stat3cKO mice). Compared to age-matched littermate controls, Stat3cKO mice of either sex (18 weeks old) exhibit reduced bone formation indices, decreased osteoblasts and increased osteoclasts, and altered material properties, without detectable changes in bone mineral density (BMD) or content of either trabecular or cortical bone. In addition, Stat3cKO mice of either sex show significantly decreased load-induced bone formation. Furthermore, pharmacologic inhibition of Stat3 in osteocytes in vitro with WP1066 blocked the increase in cytosolic calcium induced by ATP, a mediator of the cellular responses to sheer stress. WP1066 also increased reactive oxygen species (ROS) production in cultured MLO-Y4 osteocytes. These data demonstrate that Stat3 is a critical mediator of mechanical signals received by osteocytes and suggest that osteocytic Stat3 is a potential therapeutic target to stimulate bone anabolism. Elsevier 2019-07-29 /pmc/articles/PMC6700265/ /pubmed/31440530 http://dx.doi.org/10.1016/j.bonr.2019.100218 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Corry, Kylie A. Zhou, Hongkang Brustovetsky, Tatiana Himes, Evan R. Bivi, Nicoletta Horn, M. Ryne Kitase, Yukiko Wallace, Joseph M. Bellido, Teresita Brustovetsky, Nickolay Li, Jiliang Stat3 in osteocytes mediates osteogenic response to loading |
title | Stat3 in osteocytes mediates osteogenic response to loading |
title_full | Stat3 in osteocytes mediates osteogenic response to loading |
title_fullStr | Stat3 in osteocytes mediates osteogenic response to loading |
title_full_unstemmed | Stat3 in osteocytes mediates osteogenic response to loading |
title_short | Stat3 in osteocytes mediates osteogenic response to loading |
title_sort | stat3 in osteocytes mediates osteogenic response to loading |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700265/ https://www.ncbi.nlm.nih.gov/pubmed/31440530 http://dx.doi.org/10.1016/j.bonr.2019.100218 |
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