Cargando…
Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products
Bone loss occurs in astronauts during long-term space flight, but the mechanisms are still unclear. We previously showed that advanced glycation end products (AGEs) were involved in microgravity-induced osteoporosis. Here, we investigated the improvement effects of blocking AGEs formation on microgr...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003672/ https://www.ncbi.nlm.nih.gov/pubmed/36902384 http://dx.doi.org/10.3390/ijms24054953 |
_version_ | 1784904658718818304 |
---|---|
author | Liu, Cong-Jin Yang, Xiao Wang, Shou-Hui Wu, Xin-Tong Mao, Yan Shi, Jing-Wen Fan, Yu-Bo Sun, Lian-Wen |
author_facet | Liu, Cong-Jin Yang, Xiao Wang, Shou-Hui Wu, Xin-Tong Mao, Yan Shi, Jing-Wen Fan, Yu-Bo Sun, Lian-Wen |
author_sort | Liu, Cong-Jin |
collection | PubMed |
description | Bone loss occurs in astronauts during long-term space flight, but the mechanisms are still unclear. We previously showed that advanced glycation end products (AGEs) were involved in microgravity-induced osteoporosis. Here, we investigated the improvement effects of blocking AGEs formation on microgravity-induced bone loss by using the AGEs formation inhibitor, irbesartan. To achieve this objective, we used a tail-suspended (TS) rat model to simulate microgravity and treated the TS rats with 50 mg/kg/day irbesartan, as well as the fluorochrome biomarkers injected into rats to label dynamic bone formation. To assess the accumulation of AGEs, pentosidine (PEN), non-enzymatic cross-links (NE−xLR), and fluorescent AGEs (fAGEs) were identified in the bone; 8-hydroxydeoxyguanosine (8-OHdG) was analyzed for the reactive oxygen species (ROS) level in the bone. Meanwhile, bone mechanical properties, bone microstructure, and dynamic bone histomorphometry were tested for bone quality assessment, and Osterix and TRAP were immunofluorescences stained for the activities of osteoblastic and osteoclastic cells. Results showed AGEs increased significantly and 8-OHdG expression in bone showed an upward trend in TS rat hindlimbs. The bone quality (bone microstructure and mechanical properties) and bone formation process (dynamic bone formation and osteoblastic cells activities) were inhibited after tail-suspension, and showed a correlation with AGEs, suggesting the elevated AGEs contributed to the disused bone loss. After being treated with irbesartan, the increased AGEs and 8-OHdG expression were significantly inhibited, suggesting irbesartan may reduce ROS to inhibit dicarbonyl compounds, thus suppressing AGEs production after tail-suspension. The inhibition of AGEs can partially alter the bone remodeling process and improve bone quality. Both AGEs accumulation and bone alterations almost occurred in trabecular bone but not in cortical bone, suggesting AGEs effects on bone remodeling under microgravity are dependent on the biological milieu. |
format | Online Article Text |
id | pubmed-10003672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100036722023-03-11 Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products Liu, Cong-Jin Yang, Xiao Wang, Shou-Hui Wu, Xin-Tong Mao, Yan Shi, Jing-Wen Fan, Yu-Bo Sun, Lian-Wen Int J Mol Sci Article Bone loss occurs in astronauts during long-term space flight, but the mechanisms are still unclear. We previously showed that advanced glycation end products (AGEs) were involved in microgravity-induced osteoporosis. Here, we investigated the improvement effects of blocking AGEs formation on microgravity-induced bone loss by using the AGEs formation inhibitor, irbesartan. To achieve this objective, we used a tail-suspended (TS) rat model to simulate microgravity and treated the TS rats with 50 mg/kg/day irbesartan, as well as the fluorochrome biomarkers injected into rats to label dynamic bone formation. To assess the accumulation of AGEs, pentosidine (PEN), non-enzymatic cross-links (NE−xLR), and fluorescent AGEs (fAGEs) were identified in the bone; 8-hydroxydeoxyguanosine (8-OHdG) was analyzed for the reactive oxygen species (ROS) level in the bone. Meanwhile, bone mechanical properties, bone microstructure, and dynamic bone histomorphometry were tested for bone quality assessment, and Osterix and TRAP were immunofluorescences stained for the activities of osteoblastic and osteoclastic cells. Results showed AGEs increased significantly and 8-OHdG expression in bone showed an upward trend in TS rat hindlimbs. The bone quality (bone microstructure and mechanical properties) and bone formation process (dynamic bone formation and osteoblastic cells activities) were inhibited after tail-suspension, and showed a correlation with AGEs, suggesting the elevated AGEs contributed to the disused bone loss. After being treated with irbesartan, the increased AGEs and 8-OHdG expression were significantly inhibited, suggesting irbesartan may reduce ROS to inhibit dicarbonyl compounds, thus suppressing AGEs production after tail-suspension. The inhibition of AGEs can partially alter the bone remodeling process and improve bone quality. Both AGEs accumulation and bone alterations almost occurred in trabecular bone but not in cortical bone, suggesting AGEs effects on bone remodeling under microgravity are dependent on the biological milieu. MDPI 2023-03-03 /pmc/articles/PMC10003672/ /pubmed/36902384 http://dx.doi.org/10.3390/ijms24054953 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Cong-Jin Yang, Xiao Wang, Shou-Hui Wu, Xin-Tong Mao, Yan Shi, Jing-Wen Fan, Yu-Bo Sun, Lian-Wen Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products |
title | Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products |
title_full | Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products |
title_fullStr | Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products |
title_full_unstemmed | Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products |
title_short | Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products |
title_sort | preventing disused bone loss through inhibition of advanced glycation end products |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003672/ https://www.ncbi.nlm.nih.gov/pubmed/36902384 http://dx.doi.org/10.3390/ijms24054953 |
work_keys_str_mv | AT liucongjin preventingdisusedbonelossthroughinhibitionofadvancedglycationendproducts AT yangxiao preventingdisusedbonelossthroughinhibitionofadvancedglycationendproducts AT wangshouhui preventingdisusedbonelossthroughinhibitionofadvancedglycationendproducts AT wuxintong preventingdisusedbonelossthroughinhibitionofadvancedglycationendproducts AT maoyan preventingdisusedbonelossthroughinhibitionofadvancedglycationendproducts AT shijingwen preventingdisusedbonelossthroughinhibitionofadvancedglycationendproducts AT fanyubo preventingdisusedbonelossthroughinhibitionofadvancedglycationendproducts AT sunlianwen preventingdisusedbonelossthroughinhibitionofadvancedglycationendproducts |