Critical signaling pathways in osteoclast differentiation and bone resorption: mechanisms and therapeutic implications for periprosthetic osteolysis
Bone homeostasis is dynamically regulated by the balance between osteoclast-mediated bone resorption and osteoblast-driven bone formation. Periprosthetic osteolysis (PPO), a major complication following joint arthroplasty, occurs when excessive bone resorption surpasses formation, leading to implant...
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| Format: | Article |
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1639430/full |
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| author | Liangzi Yin Liangzi Yin Chenglin Sun Junjie Zhang Yan Li Yansheng Wang Yansheng Wang Lunhao Bai Zeming Lei Zeming Lei |
| author_facet | Liangzi Yin Liangzi Yin Chenglin Sun Junjie Zhang Yan Li Yansheng Wang Yansheng Wang Lunhao Bai Zeming Lei Zeming Lei |
| author_sort | Liangzi Yin |
| collection | DOAJ |
| description | Bone homeostasis is dynamically regulated by the balance between osteoclast-mediated bone resorption and osteoblast-driven bone formation. Periprosthetic osteolysis (PPO), a major complication following joint arthroplasty, occurs when excessive bone resorption surpasses formation, leading to implant loosening and failure. Emerging evidence highlights the pivotal roles of the RANKL/RANK/OPG axis, nuclear factor-κB (NF-κB) signaling, and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) cascades in osteoclast differentiation and pathological bone resorption. This review systematically explores the molecular mechanisms by which these pathways regulate osteoclastogenesis and their pathological contributions to PPO. Specifically, we analyze how wear particle-induced inflammation reprograms these signaling networks to exacerbate osteolytic activity. Furthermore, we discuss potential therapeutic strategies targeting these pathways, including pharmacological inhibitors, gene therapy, and dual-target interventions, to restore bone homeostasis. By integrating recent advances in osteoimmunology and translational research, this work provides a comprehensive framework for understanding PPO pathogenesis and developing precision therapies. |
| format | Article |
| id | doaj-art-8504a8237acf4e0faece2aa0075cd022 |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-8504a8237acf4e0faece2aa0075cd0222025-08-26T05:28:14ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-08-011310.3389/fcell.2025.16394301639430Critical signaling pathways in osteoclast differentiation and bone resorption: mechanisms and therapeutic implications for periprosthetic osteolysisLiangzi Yin0Liangzi Yin1Chenglin Sun2Junjie Zhang3Yan Li4Yansheng Wang5Yansheng Wang6Lunhao Bai7Zeming Lei8Zeming Lei9Central Laboratory, Central Hospital Affiliated to Shenyang Medical College, Shenyang, ChinaLaboratory for Hand Bone and Joint Disease, Shenyang Institute of Hand Surgery, Shenyang, ChinaCentral Laboratory, Central Hospital Affiliated to Shenyang Medical College, Shenyang, ChinaDepartment of Pathology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, ChinaCentral Laboratory, Central Hospital Affiliated to Shenyang Medical College, Shenyang, ChinaLaboratory for Hand Bone and Joint Disease, Shenyang Institute of Hand Surgery, Shenyang, ChinaDepartment of Hand Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, ChinaDepartment of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Hand Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, ChinaDepartment of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, ChinaBone homeostasis is dynamically regulated by the balance between osteoclast-mediated bone resorption and osteoblast-driven bone formation. Periprosthetic osteolysis (PPO), a major complication following joint arthroplasty, occurs when excessive bone resorption surpasses formation, leading to implant loosening and failure. Emerging evidence highlights the pivotal roles of the RANKL/RANK/OPG axis, nuclear factor-κB (NF-κB) signaling, and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) cascades in osteoclast differentiation and pathological bone resorption. This review systematically explores the molecular mechanisms by which these pathways regulate osteoclastogenesis and their pathological contributions to PPO. Specifically, we analyze how wear particle-induced inflammation reprograms these signaling networks to exacerbate osteolytic activity. Furthermore, we discuss potential therapeutic strategies targeting these pathways, including pharmacological inhibitors, gene therapy, and dual-target interventions, to restore bone homeostasis. By integrating recent advances in osteoimmunology and translational research, this work provides a comprehensive framework for understanding PPO pathogenesis and developing precision therapies.https://www.frontiersin.org/articles/10.3389/fcell.2025.1639430/fullperiprosthetic osteolysisbone resorptionsignaling pathwaysosteoclastsRANKL/RANK/OPGNF-κB |
| spellingShingle | Liangzi Yin Liangzi Yin Chenglin Sun Junjie Zhang Yan Li Yansheng Wang Yansheng Wang Lunhao Bai Zeming Lei Zeming Lei Critical signaling pathways in osteoclast differentiation and bone resorption: mechanisms and therapeutic implications for periprosthetic osteolysis Frontiers in Cell and Developmental Biology periprosthetic osteolysis bone resorption signaling pathways osteoclasts RANKL/RANK/OPG NF-κB |
| title | Critical signaling pathways in osteoclast differentiation and bone resorption: mechanisms and therapeutic implications for periprosthetic osteolysis |
| title_full | Critical signaling pathways in osteoclast differentiation and bone resorption: mechanisms and therapeutic implications for periprosthetic osteolysis |
| title_fullStr | Critical signaling pathways in osteoclast differentiation and bone resorption: mechanisms and therapeutic implications for periprosthetic osteolysis |
| title_full_unstemmed | Critical signaling pathways in osteoclast differentiation and bone resorption: mechanisms and therapeutic implications for periprosthetic osteolysis |
| title_short | Critical signaling pathways in osteoclast differentiation and bone resorption: mechanisms and therapeutic implications for periprosthetic osteolysis |
| title_sort | critical signaling pathways in osteoclast differentiation and bone resorption mechanisms and therapeutic implications for periprosthetic osteolysis |
| topic | periprosthetic osteolysis bone resorption signaling pathways osteoclasts RANKL/RANK/OPG NF-κB |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1639430/full |
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