Article Dans Une Revue Tissue Engineering: Parts A, B, and C Année : 2009

ERK1/2 Activation Induced by Inflammatory Cytokines Compromises Effective Host Tissue Integration of Engineered Cartilage

Résumé

Objective: Proinflammatory cytokines are known to provoke degradative signaling cascades that promote extracellular matrix disintegration in articular cartilage. Because integration of the repair tissue into the surrounding native cartilage to produce a mechanically stable interface has a profound impact on the viability and functionality of the restored joint surface, this study examined the effects of proinflammatory cytokines on the properties of tissue-engineered cartilage in the context of integration. Methods: Using an established in vitro cartilage defect model, we examined the integration of chondrocyte-laden agarose constructs into native articular cartilage and the biochemical and biomechanical alterations of these implants upon treatment with interleukin 1-beta (IL1-beta) and tumor necrosis factor-alpha (TNF-alpha). Additionally, we probed extracellular regulated kinase (ERK) signaling involvement in response to proinflammatory cytokines. Results: The time-dependent accumulation of extracellular matrix and concomitant increase in Young's modulus observed in the absence of cytokines was significantly decreased upon IL1-beta and TNF-alpha treatment. Push-out test showed the highest interface strength in hybrid cultures maintained without cytokines, which was significantly lowered with IL1-beta and TNF-alpha treatment. Histological characteristics of the interface region are consistent with the biochemical findings. Treatment with an inhibitor of ERK pathway antagonized the deleterious effects caused by both cytokines. Conclusion: This study is the first to show the functional catastrophic effects of IL1-beta and TNF-alpha on the biochemical, structural, and integrative properties of tissue-engineered cartilage and their significant counteraction by the blockade of ERK signaling pathway. With the discovery of new potential chemical entities, ERK inhibitor may emerge as a new therapeutic approach for functional integration and mechanical integrity of an engineered cartilage to the host tissue and, therefore, enhance long-term viability and functionality of the restored joint surface.

Dates et versions

hal-04986389 , version 1 (11-03-2025)

Identifiants

Citer

Farida Djouad, Lars Rackwitz, Yingjie Song, Sasa Janjanin, Rocky Tuan. ERK1/2 Activation Induced by Inflammatory Cytokines Compromises Effective Host Tissue Integration of Engineered Cartilage. Tissue Engineering: Parts A, B, and C, 2009, 15 (10), pp.2825-2835. ⟨10.1089/ten.TEA.2008.0663⟩. ⟨hal-04986389⟩

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