Reduced osteoclast-derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosis
Abstract Osteoporosis is associated with excessive activity of osteoclasts. In bone turn over, most osteoclasts undergo apoptosis after bone resorption and produce a large number of apoptotic bodies (ABs). However, the biological function of osteoclast-derived apoptotic bodies (OC-ABs) in the progre...
Main Authors: | , , , , , , , |
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Nature Publishing Group
2023-04-01
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Series: | Cell Death Discovery |
Online Access: | https://doi.org/10.1038/s41420-023-01434-w |
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author | Yutong Wu Hongbo Ai Yuhang Xi Pengbin Yin Ying Qu Jianzhong Xu Ce Dou Fei Luo |
author_facet | Yutong Wu Hongbo Ai Yuhang Xi Pengbin Yin Ying Qu Jianzhong Xu Ce Dou Fei Luo |
author_sort | Yutong Wu |
collection | DOAJ |
description | Abstract Osteoporosis is associated with excessive activity of osteoclasts. In bone turn over, most osteoclasts undergo apoptosis after bone resorption and produce a large number of apoptotic bodies (ABs). However, the biological function of osteoclast-derived apoptotic bodies (OC-ABs) in the progression of osteoporosis is still unknow. In our study, we identified a reduction of OC-AB quantity in the bone marrow cavity during the progression of osteoporosis, an apoptotic body-deficient MRL/lpr mice were used to study the pro-osteogenic ability of OC-ABs. Mechanistically, OC-ABs promote osteogenesis of bone mesenchymal stem cells (BMSCs) by activating the downstream mTOR pathway via RANKL-mediated reverse signaling. Moreover, systemic infusion of exogenous OC-ABs effectively delayed the bone loss in ovariectomized (OVX) mice, validated the role of OC-ABs as bone protective factor in the pathogenesis of osteoporosis. Taken together, our study elucidates the biological function of OC-ABs in the pathological progression of osteoporotic bone loss and suggests a potential therapeutic strategy to delay bone loss. |
first_indexed | 2024-04-09T15:12:51Z |
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institution | Directory Open Access Journal |
issn | 2058-7716 |
language | English |
last_indexed | 2024-04-09T15:12:51Z |
publishDate | 2023-04-01 |
publisher | Nature Publishing Group |
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series | Cell Death Discovery |
spelling | doaj.art-66ae6d6db1364e87bbc6329e8be3077f2023-04-30T11:07:28ZengNature Publishing GroupCell Death Discovery2058-77162023-04-01911910.1038/s41420-023-01434-wReduced osteoclast-derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosisYutong Wu0Hongbo Ai1Yuhang Xi2Pengbin Yin3Ying Qu4Jianzhong Xu5Ce Dou6Fei Luo7Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Orthopedics, Chinese PLA General HospitalDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University)Abstract Osteoporosis is associated with excessive activity of osteoclasts. In bone turn over, most osteoclasts undergo apoptosis after bone resorption and produce a large number of apoptotic bodies (ABs). However, the biological function of osteoclast-derived apoptotic bodies (OC-ABs) in the progression of osteoporosis is still unknow. In our study, we identified a reduction of OC-AB quantity in the bone marrow cavity during the progression of osteoporosis, an apoptotic body-deficient MRL/lpr mice were used to study the pro-osteogenic ability of OC-ABs. Mechanistically, OC-ABs promote osteogenesis of bone mesenchymal stem cells (BMSCs) by activating the downstream mTOR pathway via RANKL-mediated reverse signaling. Moreover, systemic infusion of exogenous OC-ABs effectively delayed the bone loss in ovariectomized (OVX) mice, validated the role of OC-ABs as bone protective factor in the pathogenesis of osteoporosis. Taken together, our study elucidates the biological function of OC-ABs in the pathological progression of osteoporotic bone loss and suggests a potential therapeutic strategy to delay bone loss.https://doi.org/10.1038/s41420-023-01434-w |
spellingShingle | Yutong Wu Hongbo Ai Yuhang Xi Pengbin Yin Ying Qu Jianzhong Xu Ce Dou Fei Luo Reduced osteoclast-derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosis Cell Death Discovery |
title | Reduced osteoclast-derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosis |
title_full | Reduced osteoclast-derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosis |
title_fullStr | Reduced osteoclast-derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosis |
title_full_unstemmed | Reduced osteoclast-derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosis |
title_short | Reduced osteoclast-derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosis |
title_sort | reduced osteoclast derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosis |
url | https://doi.org/10.1038/s41420-023-01434-w |
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