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- Title
Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases.
- Authors
Wen, Ze-Qin; Lin, Jun; Xie, Wen-Qing; Shan, Yun-Han; Zhen, Ge-Hua; Li, Yu-Sheng
- Abstract
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.
- Subjects
MUSCULOSKELETAL system diseases; DEGENERATION (Pathology); ENDOPLASMIC reticulum; NUCLEUS pulposus; INTERVERTEBRAL disk; MENISCUS injuries
- Publication
Military Medical Research, 2023, Vol 10, Issue 1, p1
- ISSN
2095-7467
- Publication type
Article
- DOI
10.1186/s40779-023-00485-5