Application of Cartilage Extracellular Matrix to Enhance Therapeutic Efficacy of Methotrexate
10.1007/s13770-023-00587-0
- Author:
Jeong-Woo SEO
1
;
Sung-Han JO
;
Seon-Hwa KIM
;
Byeong-Hoon CHOI
;
Hongsik CHO
;
James J. YOO
;
Sang-Hyug PARK
Author Information
1. Department of Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan, Republic of Korea
- Publication Type:ORIGINAL ARTICLE
- From:
Tissue Engineering and Regenerative Medicine
2024;21(2):209-221
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND:Rheumatoid arthritis (RA) is characterized by chronic inflammation and joint damage. Methotrexate (MTX), a commonly used disease-modifying anti-rheumatic drug (DMARD) used in RA treatment. However, the continued use of DMARDs can cause adverse effects and result in limited therapeutic efficacy. Cartilage extracellular matrix (CECM) has anti-inflammatory and anti-vascular effects and promotes stem cell migration, adhesion, and differentiation into cartilage cells.
METHODS:CECM was assessed the dsDNA, glycosaminoglycan, collagen contents and FT-IR spectrum of CECM.Furthermore, we determined the effects of CECM and MTX on cytocompatibility in the SW 982 cells and RAW 264.7 cells. The anti-inflammatory effects of CECM and MTX were assessed using macrophage cells. Finally, we examined the in vivo effects of CECM in combination with MTX on anti-inflammation control and cartilage degradation in collageninduced arthritis model. Anti-inflammation control and cartilage degradation were assessed by measuring the serum levels of RA-related cytokines and histology.
RESULTS:CECM in combination with MTX had no effect on SW 982, effectively suppressing only RAW 264.7 activity.Moreover, anti-inflammatory effects were enhanced when low-dose MTX was combined with CECM. In a collageninduced arthritis model, low-dose MTX combined with CECM remarkably reduced RA-related and pro-inflammatory cytokine levels in the blood. Additionally, low-dose MTX combined with CECM exerted the best cartilage-preservation effects compared to those observed in the other therapy groups.
CONCLUSION:Using CECM as an adjuvant in RA treatment can augment the therapeutic effects of MTX, reduce existing drug adverse effects, and promote joint tissue regeneration.
