Tissue Eng Regen Med.
2024 Feb;21(2):209-221. 10.1007/s13770-023-00587-0.
Application of Cartilage Extracellular Matrix to Enhance Therapeutic Efficacy of Methotrexate
- Affiliations
-
- 1Department of Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan, Republic of Korea
- 2Major of Biomedical Engineering, Division of Smart Healthcare, College of Information Technology and Convergence, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan 48513, Republic of Korea
- 3Department of Orthopedic Surgery and Biomedical Engineering, University of Tennessee Health Science CenterCampbell Clinic, Memphis, TN, USA
- 4Research 151, Veterans Affairs Medical Center, Memphis, TN, USA
- 5Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
- KMID: 2553243
- DOI: http://doi.org/10.1007/s13770-023-00587-0
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.
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