Injectable, thermo-reversible and complex coacervated combination gels containing IL-1 receptor antagonis inhibits IL-1 beta-induced MMP-3 expression in human osteoarthritis chondrocytes
- Authors
- Jun, Jae-Bum; Na, Young-In; Choi, Choong Hyeok; Kim, Jang Kyoung; Kim, Yong-Hee
- Issue Date
- Sep-2008
- Publisher
- ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
- Citation
- CYTOKINE, v.43, no.3, pp.258 - 258
- Indexed
- SCIE
SCOPUS
- Journal Title
- CYTOKINE
- Volume
- 43
- Number
- 3
- Start Page
- 258
- End Page
- 258
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/171871
- DOI
- 10.1016/j.cyto.2008.07.137
- ISSN
- 1043-4666
- Abstract
- IL-1 has been implicated in degradation of articular cartilage in various arthritides including osteoarthritis (OA). Therefore, blocking of IL-1 by IL-1 receptor antagonist (IL-1Ra) may be the pathogenesis-based strategy for inhibiting degradation of cartilage matrix. We investigated the role of injectable, thermo-reversible and complex coacervated combination gels containing IL-1Ra for matrix degradation in OA.The combination gels, injectable to the joint, were formed in aqueous solution by preparing complex coacervate with IL-1Ra and cationic macromolecules, and co-formulating with methylcellulose. The gels containing IL-1Ra were positioned in upper insert of transwell system, and human OA chondrocytes were placed in lower compartment and stimulated with IL-1β. Expression of matrix metalloproteinase 3 (MMP-3) was examined by real time PCR and ELISA.Release profile of IL-1Ra from the gels showed a sustained release pattern through 6 days with minimal initial bursts. IL-1Ra-loaded gels after 5 days of formation were used. IL-1b markedly induced the expression of MMP-3 gene and protein. However, loading of combination gels containing IL-1Ra profoundly inhibited IL-1β-induced MMP-3 expression in human OA chondrocytes. We are planning to examine the effectiveness of 30 day-matured gels in degradation of extracellular matrix with articular chondrocytes and cartilage explants.We applied our optimized novel in situ gel depot system containing IL-1Ra to human OA chondrocytes in transwell system. According to our results, intraarticular injection of our gels containing IL-1Ra into OA knee will provide a prolonged therapeutic option based on the pathophysiology in the treatment of knee OA.
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