TITLE:
Roles of Galactose and Its Glycosylation Modifications in Inflammatory Arthritis
AUTHORS:
Jinyou Nie, Zeyu Hou, Fei Dou, Rongxin Meng, Taoxian Wang, Dinggui Lu
KEYWORDS:
Galactose Metabolism, Glycosylation Modification, Rheumatoid Arthritis, Osteoarthritis, Keratan Sulfate, Leloir Pathway
JOURNAL NAME:
Open Journal of Orthopedics,
Vol.15 No.9,
September
18,
2025
ABSTRACT: Disorders of galactose metabolism and the aberrant glycosylation it mediates play a central role in the pathological mechanisms of rheumatoid arthritis (RA) and osteoarthritis (OA). In RA, hypo-galactosylation (G0 glycoform) of the IgG Fc region drives synovial inflammation and bone destruction by enhancing FcγRΙ binding, hyperactivating the complement system, and promoting immune complex deposition. In OA, galactose-dependent glycosylation modifications (e.g., terminal modifications of aggrecan) maintain cartilage extracellular matrix (ECM) homeostasis. Abnormal galactose metabolism (dysfunction of the Leloir pathway, activation of the galactitol pathway) exacerbates inflammation and cellular senescence by regulating the PI3K/Akt/NF-κB signaling axis. Herein, we aim to review roles of galactose and its glycosylation modifications in inflammatory arthritis, including RA and OA, thereby providing strategies and basis for the diagnosis and treatment for inflammatory arthritis by targeting galactose-metabolizing enzymes such as B4GALT1/ GALK1 or glycosylation nodes such as Galectin-4.