Repeated (Weekly) Intra-Articular Injections of Sulfated Galactans Attenuate Cartilage Degeneration in a Rat Model of Osteoarthritis

Abstract

Osteoarthritis (OA) is a progressive joint disease characterized primarily by pain, leading to substantial impairment of quality of life. Current treatments primarily alleviate symptoms but have limited efficacy in protecting or repairing articular cartilage. Marine algae have recently gained attention in pharmaceutical research due to their diverse bioactivities. Gracilaria fisheri, a red alga, contains abundant sulfated galactans (SG) that may exert chondroprotective effects. This study investigated the effects of SG on pain-related behaviors and cartilage degeneration in a Wistar rat OA model induced by anterior cruciate ligament transection combined with medial meniscus removal (ACLT + MMx). Pain-related behaviors were monitored weekly using a hind limb weight-bearing distribution test. Four weeks post-surgery, rats received intra-articular injections (50 µL) of normal saline (NSS), hyaluronic acid (HA), or SG (2.5, 50, or 500 µg) once weekly for 4 weeks. SG administration did not significantly ameliorate pain-related behaviors. However, histopathological assessment revealed that the SG (500 µg) significantly attenuated cartilage degeneration compared to OA controls. To further examine direct cellular effects, in vitro experiments using IL-1β–induced human chondrocyte inflammation revealed that SG, in inflamed cells, suppressed matrix-degrading enzymes (MMP-1 and MMP-13) while enhancing cartilage-protective markers (COL2A1 and TIMP-1). Nonetheless, type II collagen expression in vivo remained unchanged. Collectively, these findings indicate that SG from Gracilaria fisheri exerts chondroprotective effects in experimental OA, supporting its potential as a cartilage-preserving candidate for disease-modifying strategies.