Degenerative musculoskeletal diseases are structural and functional failures of the musculoskeletal system,including osteoarthritis,osteoporosis,intervertebral disc degeneration(IVDD),and sarcopenia.As the global popu...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.展开更多
Degenerative disc disease is a multifaceted progressive irreversible condition and an inevitable part of aging,which has been found to be a contributing factor for low back pain and might cause radiculopathy,myelopath...Degenerative disc disease is a multifaceted progressive irreversible condition and an inevitable part of aging,which has been found to be a contributing factor for low back pain and might cause radiculopathy,myelopathy,spinal stenosis,degenerative spondylolisthesis,and herniations.Its etiology is complex and multifactorial.Although genetics influence more dominant,the occupational and mechanical influences still persist as a major risk factor.This review emphasizes up-to-date knowledge regarding etiology of disc degeneration with special consideration on occupational,lifestyle factors,and genetic polymorphisms.展开更多
基金supported by the National Natural Science Foundation of China(92268115,82072506,81874030,82172387,82372371,82371989)the Science and Technology Innovation Program of Hunan Province(2021RC3025)+3 种基金the Natural Science Foundation of Jiangsu Province(BK20230066)the Suzhou Science and Technology Development Plan(SKY2023035,SZM2023008)the Gusu Health Talents Program(GSWS2020023)the Innovation Project for Postgraduate Students of Central South University(1053320221391,1053320231273).
文摘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.
文摘Degenerative disc disease is a multifaceted progressive irreversible condition and an inevitable part of aging,which has been found to be a contributing factor for low back pain and might cause radiculopathy,myelopathy,spinal stenosis,degenerative spondylolisthesis,and herniations.Its etiology is complex and multifactorial.Although genetics influence more dominant,the occupational and mechanical influences still persist as a major risk factor.This review emphasizes up-to-date knowledge regarding etiology of disc degeneration with special consideration on occupational,lifestyle factors,and genetic polymorphisms.
