Abstract
O-linked beta-N-acetylglucosamine glycosylation (O-GlcNAcylation), a post-translational modification of proteins, occurs in multiple physiological and pathological processes. Despite comprehensive study of protein modifications, such as phosphorylation, acetylation, and ubiquitination in musculoskeletal diseases, the role of O-GlcNAcylation in this field has been largely overlooked. However, in recent years, several studies have initially elucidated the biological mechanisms through which O-GlcNAcylation regulates the development and progress of musculoskeletal diseases, including osteoarthritis, osteoporosis, osteosarcoma, and intervertebral disc degeneration. This review aims to systematically and comprehensively summarize the existing evidence, sketching the contours of the underlying mechanisms and related signaling pathways, discussing the limitations and controversies, and providing guidance for future studies on the role of O-GlcNAcylation modifications in musculoskeletal diseases.