From death to birth: how osteocyte death promotes osteoclast formation

Bone remodeling is a dynamic and continuous process involving three components: bone formation mediated by osteoblasts, bone resorption mediated by osteoclasts, and bone formation-resorption balancing regulated by osteocytes. Excessive osteocyte death is found in various bone diseases, such as postm...

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Main Authors: Weijie Zhao, Jiale Qian, Ji Li, Tian Su, Xiaozhong Deng, Yonghua Fu, Xuelong Liang, Hongwang Cui
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1551542/full
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author Weijie Zhao
Jiale Qian
Ji Li
Tian Su
Tian Su
Xiaozhong Deng
Yonghua Fu
Xuelong Liang
Hongwang Cui
author_facet Weijie Zhao
Jiale Qian
Ji Li
Tian Su
Tian Su
Xiaozhong Deng
Yonghua Fu
Xuelong Liang
Hongwang Cui
author_sort Weijie Zhao
collection DOAJ
description Bone remodeling is a dynamic and continuous process involving three components: bone formation mediated by osteoblasts, bone resorption mediated by osteoclasts, and bone formation-resorption balancing regulated by osteocytes. Excessive osteocyte death is found in various bone diseases, such as postmenopausal osteoporosis (PMOP), and osteoclasts are found increased and activated at osteocyte death sites. Currently, apart from apoptosis and necrosis as previously established, more forms of cell death are reported, including necroptosis, ferroptosis and pyroptosis. These forms of cell death play important role in the development of inflammatory diseases and bone diseases. Increasing studies have revealed that various forms of osteocyte death promote osteoclast formation via different mechanism, including actively secreting pro-inflammatory and pro-osteoclastogenic cytokines, such as tumor necrosis factor alpha (TNF-α) and receptor activator of nuclear factor-kappa B ligand (RANKL), or passively releasing pro-inflammatory damage associated molecule patterns (DAMPs), such as high mobility group box 1 (HMGB1). This review summarizes the established and potential mechanisms by which various forms of osteocyte death regulate osteoclast formation, aiming to provide better understanding of bone disease development and therapeutic target.
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publishDate 2025-03-01
publisher Frontiers Media S.A.
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series Frontiers in Immunology
spelling doaj-art-a758e87d4ccd43f4b11c0669ce1c00562025-08-20T02:55:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15515421551542From death to birth: how osteocyte death promotes osteoclast formationWeijie Zhao0Jiale Qian1Ji Li2Tian Su3Tian Su4Xiaozhong Deng5Yonghua Fu6Xuelong Liang7Hongwang Cui8Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Emergency Surgery, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital, Hainan Medical University, Haikou, ChinaKey Laboratory of Emergency and Trauma of Ministry of Education, Department of Emergency Surgery, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital, Hainan Medical University, Haikou, ChinaKey Laboratory of Emergency and Trauma of Ministry of Education, Department of Emergency Surgery, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital, Hainan Medical University, Haikou, ChinaKey Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, ChinaEngineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Emergency and Trauma, College of pharmacy, Hainan Medical University, Haikou, ChinaDepartment of Pain Treatment, Nanxi Shan Hospital of Guangxi Zhuang Autonomous Region, Guilin, ChinaDepartment of Hand and Foot Microsurgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaThe First School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaKey Laboratory of Emergency and Trauma of Ministry of Education, Department of Emergency Surgery, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital, Hainan Medical University, Haikou, ChinaBone remodeling is a dynamic and continuous process involving three components: bone formation mediated by osteoblasts, bone resorption mediated by osteoclasts, and bone formation-resorption balancing regulated by osteocytes. Excessive osteocyte death is found in various bone diseases, such as postmenopausal osteoporosis (PMOP), and osteoclasts are found increased and activated at osteocyte death sites. Currently, apart from apoptosis and necrosis as previously established, more forms of cell death are reported, including necroptosis, ferroptosis and pyroptosis. These forms of cell death play important role in the development of inflammatory diseases and bone diseases. Increasing studies have revealed that various forms of osteocyte death promote osteoclast formation via different mechanism, including actively secreting pro-inflammatory and pro-osteoclastogenic cytokines, such as tumor necrosis factor alpha (TNF-α) and receptor activator of nuclear factor-kappa B ligand (RANKL), or passively releasing pro-inflammatory damage associated molecule patterns (DAMPs), such as high mobility group box 1 (HMGB1). This review summarizes the established and potential mechanisms by which various forms of osteocyte death regulate osteoclast formation, aiming to provide better understanding of bone disease development and therapeutic target.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1551542/fullosteocytenecrosisapoptosisnecroptosisferroptosispyroptosis
spellingShingle Weijie Zhao
Jiale Qian
Ji Li
Tian Su
Tian Su
Xiaozhong Deng
Yonghua Fu
Xuelong Liang
Hongwang Cui
From death to birth: how osteocyte death promotes osteoclast formation
Frontiers in Immunology
osteocyte
necrosis
apoptosis
necroptosis
ferroptosis
pyroptosis
title From death to birth: how osteocyte death promotes osteoclast formation
title_full From death to birth: how osteocyte death promotes osteoclast formation
title_fullStr From death to birth: how osteocyte death promotes osteoclast formation
title_full_unstemmed From death to birth: how osteocyte death promotes osteoclast formation
title_short From death to birth: how osteocyte death promotes osteoclast formation
title_sort from death to birth how osteocyte death promotes osteoclast formation
topic osteocyte
necrosis
apoptosis
necroptosis
ferroptosis
pyroptosis
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1551542/full
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