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

**Authors:** Nirada Srianake, Amarin Thongsuk, Scarlett Desclaux, Thitiya Phuagpan, Jiraporn Sriwong, Alita Kongchanagul, Wanwisa Himakhun, Ruedee Hemstapat, Kanokpan Wongprasert

PMC · DOI: 10.1002/jor.70175 · Journal of Orthopaedic Research · 2026-03-09

## TL;DR

Sulfated galactans from a red alga reduced cartilage degeneration in a rat model of osteoarthritis, suggesting potential for joint protection.

## Contribution

Demonstrates sulfated galactans from Gracilaria fisheri can preserve cartilage in osteoarthritis models.

## Key findings

- SG at 500 µg significantly attenuated cartilage degeneration in OA rats.
- SG suppressed matrix-degrading enzymes and enhanced cartilage-protective markers in human chondrocytes.
- SG treatment improved cartilage structure preservation in histological assessments.

## 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.

Knee osteoarthritis (OA) is characterized by progressive cartilage degeneration and remains a major cause of joint dysfunction with limited disease‐modifying therapies. This study evaluated the therapeutic potential of sulfated galactans (SG) extracted from Gracilaria fisheri in a rat OA model induced by anterior cruciate ligament transection and medial meniscectomy (ACLT+MMx). Following periodic intra‐articular SG administration, cartilage degeneration was assessed using histological staining (H&E, Safranin‐O/Fast Green) and collagen type II immunohistochemistry. SG treatment was associated with delayed cartilage degeneration and improved preservation of cartilage structure.

## Linked entities

- **Genes:** MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312], MMP13 (matrix metallopeptidase 13) [NCBI Gene 4322], COL2A1 (collagen type II alpha 1 chain) [NCBI Gene 1280], TIMP1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 7076]
- **Diseases:** osteoarthritis (MONDO:0005178)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Col2a1 (collagen type II alpha 1 chain) [NCBI Gene 25412] {aka CG2A1A, COLLII}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, TIMP1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 7076] {aka CLGI, EPA, EPO, HCI, TIMP, TIMP-1}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, MMP13 (matrix metallopeptidase 13) [NCBI Gene 4322] {aka CLG3, MANDP1, MDST, MMP-13}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277] {aka CAFYD, EDSARTH1, EDSC, OI1, OI2, OI3}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}, Timp1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 116510] {aka TIMP-1, Timp}, COL2A1 (collagen type II alpha 1 chain) [NCBI Gene 1280] {aka ACG2, ANFH, ANFH1, AOM, COL11A3, EDMMD}, Mmp13 (matrix metallopeptidase 13) [NCBI Gene 171052], Mmp1 (matrix metallopeptidase 1) [NCBI Gene 300339] {aka Clgn, MMP-1, Mmp1a}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}, Acan (aggrecan) [NCBI Gene 58968] {aka Agc, Agc1}
- **Diseases:** stiffness (MESH:C566112), OA pain (MESH:D010146), inflammation (MESH:D007249), trauma (MESH:D014947), degenerative joint disease (MESH:D019636), cytotoxic (MESH:D064420), joint disease (MESH:D007592), bone damage (MESH:D001847), Knee OA (MESH:D020370), erosions (MESH:D014077), Knee joint pain (MESH:D018771), anterior cruciate ligament (MESH:D000070598), nociceptive (MESH:D059226), infection (MESH:D007239), postoperative pain (MESH:D010149), sclerosis (MESH:D012598), gain (MESH:D015430), OARSI (MESH:C000719191), structural degeneration (MESH:D020914), overdose (MESH:D062787), Cartilage (MESH:D002357), MCL (MESH:D020423), OA (MESH:D010003), NSS (MESH:C537354)
- **Chemicals:** sodium citrate (MESH:D000077559), thiopental (MESH:D013874), glycosaminoglycans (MESH:D006025), Hematoxylin (MESH:D006416), sulfate (MESH:D013431), oxygen (MESH:D010100), paraffin (MESH:D010232), hydrogen peroxide (MESH:D006861), SG (-), H&amp;E (MESH:D006371), methanol (MESH:D000432), Safranin O (MESH:C009195), Fast Green (MESH:C035906), carbohydrate (MESH:D002241), acetone (MESH:D000096), polymers (MESH:D011108), G4S (MESH:D004003), fucoidan (MESH:C007789), polysaccharides (MESH:D011134), xylazine (MESH:D014991), EDTA (MESH:D004492), isoflurane (MESH:D007530), cefazolin (MESH:D002437), benzene (MESH:D001554), water (MESH:D014867), DEAE (MESH:C007369), CO2 (MESH:D002245), formalin (MESH:D005557), ethanol (MESH:D000431), povidone-iodine (MESH:D011206), HA (MESH:D006820), d-galactopyranose (MESH:D005690), Tween 20 (MESH:D011136), eosin (MESH:D004801), biotin (MESH:D001710), 3, 3'-diaminobenzidine (MESH:D015100), DAB (MESH:C000469)
- **Species:** Sargassum (genus) [taxon 3015], Gracilaria caudata (species) [taxon 2572395], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Phaeophyceae (brown algae, class) [taxon 2870], Rhodophyta (red algae, phylum) [taxon 2763], Gracilaria fisheri (species) [taxon 1232878], Gelidium crinale (species) [taxon 143013]
- **Mutations:** C-6 of G
- **Cell lines:** MUSC66-061-691 — Mus musculus (Mouse), Hybridoma (CVCL_B6QD), C28/I2 — Homo sapiens (Human), Transformed cell line (CVCL_0187)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12972601/full.md

## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12972601/full.md

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Source: https://tomesphere.com/paper/PMC12972601