Cuproptosis and its potential role in musculoskeletal disease
Cuproptosis, a recently identified form of copper-dependent cell death, arises from intracellular copper dyshomeostasis. As an essential trace element, copper plays a critical role in bioenergetic metabolism, redox regulation, and synaptic transmission. However, excessive copper exerts cytotoxic eff...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1570131/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849739269592055808 |
|---|---|
| author | Ziyang Xiang Huiling Mei Honglin Wang Xiaoyue Yao Ji Rao Wentao Zhang Aoshuang Xu Lin Lu |
| author_facet | Ziyang Xiang Huiling Mei Honglin Wang Xiaoyue Yao Ji Rao Wentao Zhang Aoshuang Xu Lin Lu |
| author_sort | Ziyang Xiang |
| collection | DOAJ |
| description | Cuproptosis, a recently identified form of copper-dependent cell death, arises from intracellular copper dyshomeostasis. As an essential trace element, copper plays a critical role in bioenergetic metabolism, redox regulation, and synaptic transmission. However, excessive copper exerts cytotoxic effects through multiple pathways, including increased reactive oxygen species (ROS) production, apoptotic cascade activation, necrotic membrane rupture, inflammatory responses, and mitochondrial dysfunction. Distinct from other cell death mechanisms, cuproptosis is characterized by copper ion binding to acetylated mitochondrial respiratory chain proteins, leading to pathogenic protein aggregation, iron-sulfur cluster depletion, and cellular collapse. Emerging evidence underscores aberrant copper accumulation and resultant proteotoxic stress as pivotal contributors to the pathogenesis of multiple musculoskeletal pathologies, including osteoporosis, osteoarthritis, sarcopenia, osteosarcoma, intervertebral disc degeneration, spinal cord injury, and biofilm-associated orthopedic infections. Understanding the spatiotemporal regulation of cuproptosis may provide novel opportunities for advancing diagnostic and therapeutic approaches in orthopedic medicine. This review synthesizes current insights into the molecular mechanisms of cuproptosis, its pathogenic role in musculoskeletal diseases, and the potential for biomarker-driven therapeutic interventions. |
| format | Article |
| id | doaj-art-8f3cfdba3a6e4ebe973c9af47ee7e91e |
| institution | DOAJ |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-8f3cfdba3a6e4ebe973c9af47ee7e91e2025-08-20T03:06:19ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-04-011310.3389/fcell.2025.15701311570131Cuproptosis and its potential role in musculoskeletal diseaseZiyang Xiang0Huiling Mei1Honglin Wang2Xiaoyue Yao3Ji Rao4Wentao Zhang5Aoshuang Xu6Lin Lu7Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Orthopaedics Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaCuproptosis, a recently identified form of copper-dependent cell death, arises from intracellular copper dyshomeostasis. As an essential trace element, copper plays a critical role in bioenergetic metabolism, redox regulation, and synaptic transmission. However, excessive copper exerts cytotoxic effects through multiple pathways, including increased reactive oxygen species (ROS) production, apoptotic cascade activation, necrotic membrane rupture, inflammatory responses, and mitochondrial dysfunction. Distinct from other cell death mechanisms, cuproptosis is characterized by copper ion binding to acetylated mitochondrial respiratory chain proteins, leading to pathogenic protein aggregation, iron-sulfur cluster depletion, and cellular collapse. Emerging evidence underscores aberrant copper accumulation and resultant proteotoxic stress as pivotal contributors to the pathogenesis of multiple musculoskeletal pathologies, including osteoporosis, osteoarthritis, sarcopenia, osteosarcoma, intervertebral disc degeneration, spinal cord injury, and biofilm-associated orthopedic infections. Understanding the spatiotemporal regulation of cuproptosis may provide novel opportunities for advancing diagnostic and therapeutic approaches in orthopedic medicine. This review synthesizes current insights into the molecular mechanisms of cuproptosis, its pathogenic role in musculoskeletal diseases, and the potential for biomarker-driven therapeutic interventions.https://www.frontiersin.org/articles/10.3389/fcell.2025.1570131/fullcuproptosisosteoporosisosteoarthritisosteosarcomaintervertebral disc degenerationspinal cord injury |
| spellingShingle | Ziyang Xiang Huiling Mei Honglin Wang Xiaoyue Yao Ji Rao Wentao Zhang Aoshuang Xu Lin Lu Cuproptosis and its potential role in musculoskeletal disease Frontiers in Cell and Developmental Biology cuproptosis osteoporosis osteoarthritis osteosarcoma intervertebral disc degeneration spinal cord injury |
| title | Cuproptosis and its potential role in musculoskeletal disease |
| title_full | Cuproptosis and its potential role in musculoskeletal disease |
| title_fullStr | Cuproptosis and its potential role in musculoskeletal disease |
| title_full_unstemmed | Cuproptosis and its potential role in musculoskeletal disease |
| title_short | Cuproptosis and its potential role in musculoskeletal disease |
| title_sort | cuproptosis and its potential role in musculoskeletal disease |
| topic | cuproptosis osteoporosis osteoarthritis osteosarcoma intervertebral disc degeneration spinal cord injury |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1570131/full |
| work_keys_str_mv | AT ziyangxiang cuproptosisanditspotentialroleinmusculoskeletaldisease AT huilingmei cuproptosisanditspotentialroleinmusculoskeletaldisease AT honglinwang cuproptosisanditspotentialroleinmusculoskeletaldisease AT xiaoyueyao cuproptosisanditspotentialroleinmusculoskeletaldisease AT jirao cuproptosisanditspotentialroleinmusculoskeletaldisease AT wentaozhang cuproptosisanditspotentialroleinmusculoskeletaldisease AT aoshuangxu cuproptosisanditspotentialroleinmusculoskeletaldisease AT linlu cuproptosisanditspotentialroleinmusculoskeletaldisease |