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Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis

Exercise results in mechanical loading of the bone and stimulates energy expenditure in the adipose tissue. It is therefore likely that the bone secretes factors to communicate with adipose tissue in response to mechanical loading. Interleukin (IL)−11 is known to be expressed in the bone, it is upre...

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Autores principales: Dong, Bingzi, Hiasa, Masahiro, Higa, Yoshiki, Ohnishi, Yukiyo, Endo, Itsuro, Kondo, Takeshi, Takashi, Yuichi, Tsoumpra, Maria, Kainuma, Risa, Sawatsubashi, Shun, Kiyonari, Hiroshi, Shioi, Go, Sakaue, Hiroshi, Nakashima, Tomoki, Kato, Shigeaki, Abe, Masahiro, Fukumoto, Seiji, Matsumoto, Toshio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691688/
https://www.ncbi.nlm.nih.gov/pubmed/36424386
http://dx.doi.org/10.1038/s41467-022-34869-3
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author Dong, Bingzi
Hiasa, Masahiro
Higa, Yoshiki
Ohnishi, Yukiyo
Endo, Itsuro
Kondo, Takeshi
Takashi, Yuichi
Tsoumpra, Maria
Kainuma, Risa
Sawatsubashi, Shun
Kiyonari, Hiroshi
Shioi, Go
Sakaue, Hiroshi
Nakashima, Tomoki
Kato, Shigeaki
Abe, Masahiro
Fukumoto, Seiji
Matsumoto, Toshio
author_facet Dong, Bingzi
Hiasa, Masahiro
Higa, Yoshiki
Ohnishi, Yukiyo
Endo, Itsuro
Kondo, Takeshi
Takashi, Yuichi
Tsoumpra, Maria
Kainuma, Risa
Sawatsubashi, Shun
Kiyonari, Hiroshi
Shioi, Go
Sakaue, Hiroshi
Nakashima, Tomoki
Kato, Shigeaki
Abe, Masahiro
Fukumoto, Seiji
Matsumoto, Toshio
author_sort Dong, Bingzi
collection PubMed
description Exercise results in mechanical loading of the bone and stimulates energy expenditure in the adipose tissue. It is therefore likely that the bone secretes factors to communicate with adipose tissue in response to mechanical loading. Interleukin (IL)−11 is known to be expressed in the bone, it is upregulated by mechanical loading, enhances osteogenesis and suppresses adipogenesis. Here, we show that systemic IL-11 deletion (IL-11(−/−)) results in reduced bone mass, suppressed bone formation response to mechanical loading, enhanced expression of Wnt inhibitors, and suppressed Wnt signaling. At the same time, the enhancement of bone resorption by mechanical unloading was unaffected. Unexpectedly, IL-11(−/−) mice have increased systemic adiposity and glucose intolerance. Osteoblast/osteocyte-specific IL-11 deletion in osteocalcin-Cre;IL-11(fl/fl) mice have reduced serum IL-11 levels, blunted bone formation under mechanical loading, and increased systemic adiposity similar to IL-11(−/−) mice. Adipocyte-specific IL-11 deletion in adiponectin-Cre;IL-11(fl/fl) did not exhibit any abnormalities. We demonstrate that osteoblast/osteocyte-derived IL-11 controls both osteogenesis and systemic adiposity in response to mechanical loading, an important insight for our understanding of osteoporosis and metabolic syndromes.
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spelling pubmed-96916882022-11-26 Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis Dong, Bingzi Hiasa, Masahiro Higa, Yoshiki Ohnishi, Yukiyo Endo, Itsuro Kondo, Takeshi Takashi, Yuichi Tsoumpra, Maria Kainuma, Risa Sawatsubashi, Shun Kiyonari, Hiroshi Shioi, Go Sakaue, Hiroshi Nakashima, Tomoki Kato, Shigeaki Abe, Masahiro Fukumoto, Seiji Matsumoto, Toshio Nat Commun Article Exercise results in mechanical loading of the bone and stimulates energy expenditure in the adipose tissue. It is therefore likely that the bone secretes factors to communicate with adipose tissue in response to mechanical loading. Interleukin (IL)−11 is known to be expressed in the bone, it is upregulated by mechanical loading, enhances osteogenesis and suppresses adipogenesis. Here, we show that systemic IL-11 deletion (IL-11(−/−)) results in reduced bone mass, suppressed bone formation response to mechanical loading, enhanced expression of Wnt inhibitors, and suppressed Wnt signaling. At the same time, the enhancement of bone resorption by mechanical unloading was unaffected. Unexpectedly, IL-11(−/−) mice have increased systemic adiposity and glucose intolerance. Osteoblast/osteocyte-specific IL-11 deletion in osteocalcin-Cre;IL-11(fl/fl) mice have reduced serum IL-11 levels, blunted bone formation under mechanical loading, and increased systemic adiposity similar to IL-11(−/−) mice. Adipocyte-specific IL-11 deletion in adiponectin-Cre;IL-11(fl/fl) did not exhibit any abnormalities. We demonstrate that osteoblast/osteocyte-derived IL-11 controls both osteogenesis and systemic adiposity in response to mechanical loading, an important insight for our understanding of osteoporosis and metabolic syndromes. Nature Publishing Group UK 2022-11-23 /pmc/articles/PMC9691688/ /pubmed/36424386 http://dx.doi.org/10.1038/s41467-022-34869-3 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
Dong, Bingzi
Hiasa, Masahiro
Higa, Yoshiki
Ohnishi, Yukiyo
Endo, Itsuro
Kondo, Takeshi
Takashi, Yuichi
Tsoumpra, Maria
Kainuma, Risa
Sawatsubashi, Shun
Kiyonari, Hiroshi
Shioi, Go
Sakaue, Hiroshi
Nakashima, Tomoki
Kato, Shigeaki
Abe, Masahiro
Fukumoto, Seiji
Matsumoto, Toshio
Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis
title Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis
title_full Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis
title_fullStr Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis
title_full_unstemmed Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis
title_short Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis
title_sort osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691688/
https://www.ncbi.nlm.nih.gov/pubmed/36424386
http://dx.doi.org/10.1038/s41467-022-34869-3
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