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Application of Cartilage Extracellular Matrix to Enhance Therapeutic Efficacy of Methotrexate

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Tissue Engineering and Regenerative Medicine Aims and scope

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 collagen-induced 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 collagen-induced 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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Data availability

The data presented in this study are available on request from all the authors.

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Acknowledgement

This research was supported by the Pukyong National University Research Fund in 2021.

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Authors and Affiliations

  1. Department of Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan, Republic of Korea

    Jeong-Woo Seo, Sung-Han Jo, Seon-Hwa Kim, Byeong-Hoon Choi & Sang-Hyug Park

  2. Major 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

    Sang-Hyug Park

  3. Department of Orthopedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center-Campbell Clinic, Memphis, TN, USA

    Hongsik Cho

  4. Research 151, Veterans Affairs Medical Center, Memphis, TN, USA

    Hongsik Cho

  5. Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    James J. Yoo

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The animal studies were approved by the Institutional Review Board of Pukyong National University (PKNUIACUC-2022–06).

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Seo, JW., Jo, SH., Kim, SH. et al. Application of Cartilage Extracellular Matrix to Enhance Therapeutic Efficacy of Methotrexate. Tissue Eng Regen Med 21, 209–221 (2024). https://doi.org/10.1007/s13770-023-00587-0

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