Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases

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外文摘要：Degenerative musculoskeletal diseases are structural and functional failures of the musculoskeletal system,including osteoarthritis,osteoporosis,intervertebral disc degeneration(IVDD),and sarcopenia.As the global population ages,degenerative musculoskeletal diseases are becoming more prevalent.However,the pathogenesis of degenerative musculoskeletal diseases is not fully understood.Previous studies have revealed that endoplasmic reticulum(ER)stress is a stress response that occurs when impairment of the protein folding capacity of the ER leads to the accumulation of misfolded or unfolded proteins in the ER,contributing to degenerative musculoskeletal diseases.By affecting cartilage degeneration,synovitis,meniscal lesion,subchondral bone remodeling of osteoarthritis,bone remodeling and angiogenesis of osteoporosis,nucleus pulposus degeneration,annulus fibrosus rupture,cartilaginous endplate degeneration of IVDD,and sarcopenia,ER stress is involved in the pathogenesis of degenerative musculoskeletal diseases.Preclinical studies have found that regulation of ER stress can delay the progression of multiple degenerative musculoskeletal diseases.These pilot studies provide foundations for further evaluation of the feasibility,efficacy,and safety of ER stress modulators in the treatment of musculoskeletal degenerative diseases in clinical trials.In this review,we have integrated up-to-date research findings of ER stress into the pathogenesis of degenerative musculoskeletal diseases.In a future perspective,we have also discussed possible directions of ER stress in the investigation of degenerative musculoskeletal disease,potential therapeutic strategies for degenerative musculoskeletal diseases using ER stress modulators,as well as underlying challenges and obstacles in bench-to-beside research.

外文关键词：

Endoplasmic reticulum stressDegenerative musculoskeletal diseasesPathogenesisTreatment

作者：

Ze-Qin Wen、Jun Lin、Wen-Qing Xie、Yun-Han Shan、Ge-Hua Zhen、Yu-Sheng Li

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作者单位：

Department of Orthopaedics,Xiangya Hospital,Central South University,Changsha 410008,China

Xiangya School of Medicine,Central South University,Changsha 410013,China

Department of Orthopaedics,Suzhou Dushu Lake Hospital,Dushu Lake Hospital Affiliated to Soochow University,Medical Center of Soochow University,Suzhou 215001,China

National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha 410008,China

Department of General Surgery,Xiangya Hospital,Central South University,Changsha 410008,China

Department of Orthopaedic Surgery,School of Medicine,Johns Hopkins University,Baltimore,MD 21205,USA

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出版年：

2024

DOI：

10.1186/s40779-023-00485-5

军事医学研究(英文)

CSTPCD

ISSN：2095-7467

年,卷(期)：2024.11(6)