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Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss

Osteoclastogenesis is an essential process during bone metabolism which can also be promoted by inflammatory signals. Thrombomodulin (TM), a transmembrane glycoprotein, exerts anti-inflammatory activities such as neutralization of proinflammatory high-mobility group box 1 (HMGB1) through TM lectin-l...

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Autores principales: Cheng, Tsung-Lin, Lai, Chao-Han, Shieh, Shyh-Jou, Jou, Yin-Bo, Yeh, Jwu-Lai, Yang, Ai-Lun, Wang, Yan-Hsiung, Wang, Chau-Zen, Chen, Chung-Hwan, Shi, Guey-Yueh, Ho, Mei-Ling, Wu, Hua-Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911607/
https://www.ncbi.nlm.nih.gov/pubmed/27311356
http://dx.doi.org/10.1038/srep28340
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author Cheng, Tsung-Lin
Lai, Chao-Han
Shieh, Shyh-Jou
Jou, Yin-Bo
Yeh, Jwu-Lai
Yang, Ai-Lun
Wang, Yan-Hsiung
Wang, Chau-Zen
Chen, Chung-Hwan
Shi, Guey-Yueh
Ho, Mei-Ling
Wu, Hua-Lin
author_facet Cheng, Tsung-Lin
Lai, Chao-Han
Shieh, Shyh-Jou
Jou, Yin-Bo
Yeh, Jwu-Lai
Yang, Ai-Lun
Wang, Yan-Hsiung
Wang, Chau-Zen
Chen, Chung-Hwan
Shi, Guey-Yueh
Ho, Mei-Ling
Wu, Hua-Lin
author_sort Cheng, Tsung-Lin
collection PubMed
description Osteoclastogenesis is an essential process during bone metabolism which can also be promoted by inflammatory signals. Thrombomodulin (TM), a transmembrane glycoprotein, exerts anti-inflammatory activities such as neutralization of proinflammatory high-mobility group box 1 (HMGB1) through TM lectin-like domain. This study aimed to identify the role of myeloid TM (i.e., endogenous TM expression on the myeloid lineage) in osteoclastogenesis and inflammatory bone loss. Using human peripheral blood mononuclear cells and mouse bone marrow-derived macrophages, we observed that the protein levels of TM were dramatically reduced as these cells differentiated into osteoclasts. In addition, osteoclastogenesis and extracellular HMGB1 accumulation were enhanced in primary cultured monocytes from myeloid-specific TM-deficient mice (LysMcre/TM(flox/flox)) and from TM lectin-like domain deleted mice (TM(LeD/LeD)) compared with their respective controls. Micro-computerized tomography scans showed that ovariectomy-induced bone loss was more pronounced in TM(LeD/LeD) mice compared with controls. Finally, the inhibiting effects of recombinant TM lectin-like domain (rTMD1) on bone resorption in vitro, and bone loss in both the ovariectomized model and collagen antibody-induced arthritis model has been detected. These findings suggested that the myeloid TM lectin-like domain may inhibit osteoclastogenesis by reducing HMGB1 signaling, and rTMD1 may hold therapeutic potential for inflammatory bone loss.
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spelling pubmed-49116072016-06-17 Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss Cheng, Tsung-Lin Lai, Chao-Han Shieh, Shyh-Jou Jou, Yin-Bo Yeh, Jwu-Lai Yang, Ai-Lun Wang, Yan-Hsiung Wang, Chau-Zen Chen, Chung-Hwan Shi, Guey-Yueh Ho, Mei-Ling Wu, Hua-Lin Sci Rep Article Osteoclastogenesis is an essential process during bone metabolism which can also be promoted by inflammatory signals. Thrombomodulin (TM), a transmembrane glycoprotein, exerts anti-inflammatory activities such as neutralization of proinflammatory high-mobility group box 1 (HMGB1) through TM lectin-like domain. This study aimed to identify the role of myeloid TM (i.e., endogenous TM expression on the myeloid lineage) in osteoclastogenesis and inflammatory bone loss. Using human peripheral blood mononuclear cells and mouse bone marrow-derived macrophages, we observed that the protein levels of TM were dramatically reduced as these cells differentiated into osteoclasts. In addition, osteoclastogenesis and extracellular HMGB1 accumulation were enhanced in primary cultured monocytes from myeloid-specific TM-deficient mice (LysMcre/TM(flox/flox)) and from TM lectin-like domain deleted mice (TM(LeD/LeD)) compared with their respective controls. Micro-computerized tomography scans showed that ovariectomy-induced bone loss was more pronounced in TM(LeD/LeD) mice compared with controls. Finally, the inhibiting effects of recombinant TM lectin-like domain (rTMD1) on bone resorption in vitro, and bone loss in both the ovariectomized model and collagen antibody-induced arthritis model has been detected. These findings suggested that the myeloid TM lectin-like domain may inhibit osteoclastogenesis by reducing HMGB1 signaling, and rTMD1 may hold therapeutic potential for inflammatory bone loss. Nature Publishing Group 2016-06-17 /pmc/articles/PMC4911607/ /pubmed/27311356 http://dx.doi.org/10.1038/srep28340 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Cheng, Tsung-Lin
Lai, Chao-Han
Shieh, Shyh-Jou
Jou, Yin-Bo
Yeh, Jwu-Lai
Yang, Ai-Lun
Wang, Yan-Hsiung
Wang, Chau-Zen
Chen, Chung-Hwan
Shi, Guey-Yueh
Ho, Mei-Ling
Wu, Hua-Lin
Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss
title Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss
title_full Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss
title_fullStr Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss
title_full_unstemmed Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss
title_short Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss
title_sort myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911607/
https://www.ncbi.nlm.nih.gov/pubmed/27311356
http://dx.doi.org/10.1038/srep28340
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