Beyond wear and tear at the joint

• Published in: Science (American Association for the Advancement of Science) Vol. 388; no. 6742; pp. 30 - 31
• Main Author: Liu, Chuan-ju
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 04.04.2025
• Subjects: Aging (Individuals); Animals; Bile Acids and Salts - metabolism; Cartilage diseases; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Chronic pain; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - metabolism; Humans; Joint diseases; Lipid metabolism; Lipids; Metabolic pathways; Obesity; Older people; Osteoarthritis; Osteoarthritis - metabolism; Pathogenesis; Signal Transduction
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.adw4656

Bile acid metabolism meets glucagon-like peptide 1 signaling in osteoarthritis Osteoarthritis is the most prevalent joint disorder worldwide and a leading cause of chronic pain and disability in older adults. Traditionally, it has been regarded as a degenerative disease driven by mechanical wear and tear ( 1 , 2 ). However, emerging evidence highlights the role of metabolic pathways in the pathogenesis of osteoarthritis ( 3 , 4 ). For instance, obesity predisposes individuals to osteoarthritis even in non–weight-bearing joints, indicating that chronic metabolic inflammation and altered lipid metabolism—rather than mechanical overload alone—can drive cartilage breakdown. However, mechanisms underlying the links between metabolism and disease progression remain poorly understood, limiting the ability to develop new therapeutic approaches. On page 48 of this issue, Yang et al . ( 5 ) report compelling evidence for a gut-joint axis involving bile acid metabolism and glucagon-like peptide 1 (GLP-1) signaling in osteoarthritis development, advancing the understanding of osteoarthritis pathogenesis and opening new avenues for therapy.