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Enhanced intra-articular therapy for rheumatoid arthritis using click-crosslinked hyaluronic acid hydrogels loaded with toll-like receptor antagonizing peptides
- Title
- Enhanced intra-articular therapy for rheumatoid arthritis using click-crosslinked hyaluronic acid hydrogels loaded with toll-like receptor antagonizing peptides
- Authors
- Lee, Soyeon; Seo, Jiyoung; Kim, Young Hun; Ju, Hyeon Jin; Kim, Shina; Ji, Yun Bae; Lee, Hai Bang; Kim, Han Su; Choi, Sangdun; Kim, Moon Suk
- Ewha Authors
- 김한수
- SCOPUS Author ID
- 김한수
- Issue Date
- 2023
- Journal Title
- ACTA BIOMATERIALIA
- ISSN
- 1742-7061
1878-7568
- Citation
- ACTA BIOMATERIALIA vol. 172, pp. 188 - 205
- Keywords
- Rheumatoid arthritis; Toll -like receptors -antagonizing peptide; Click-crosslinking hyaluronic acid depot; Intra-articular injection; Prolonged release
- Publisher
- ELSEVIER SCI LTD
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Rheumatoid arthritis (RA) is a chronic inflammatory disorder that results in the deterioration of joint cartilage and bone. Toll-like receptor 4 (TLR4) has been pinpointed as a key factor in RA-related inflammation. While Toll-like receptor antagonizing peptide 2 (TAP2) holds potential as an anti-inflammatory agent, its in vivo degradation rate hinders its efficacy. We engineered depots of TAP2 encapsulated in click-crosslinked hyaluronic acid (TAP2+Cx-HA) for intra-articular administration, aiming to enhance the effectiveness of TAP2 as an anti-inflammatory agent within the joint cavity. Our data demonstrated that FI-TAP2+Cx-HA achieves a longer retention time in the joint cavity compared to FI-TAP2 alone. Mechanistically, we found that TAP2 interacts with TLR4 on the cell membranes of inflammatory cells, thereby inhibiting the nuclear translocation of NF-kappa B and maintaining it in an inactive cytoplasmic state. In a rat model of RA, the TAP2+Cx-HA formulation effectively downregulated the inflammatory cytokines TNF-alpha and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3 zeta. This led to a more rapid restoration of cartilage thickness, increased deposition of glycosaminoglycans, and new bone tissue formation in the regenerated cartilage, in comparison to a single TAP2 treatment after a six-week period. Our results suggest that TAP2+Cx-HA could serve as a potent intra-articular treatment for RA, offering both symptomatic relief and promoting cartilage regeneration. This innovative delivery system holds significant promise for improving the management of RA and other inflammatory joint conditions.
- DOI
- 10.1016/j.actbio.2023.10.023|http://dx.doi.org/10.1016/j.actbio.2023.10.023
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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