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. 1992 Aug;90(2):488–496. doi: 10.1172/JCI115885

Monocyte chemoattractant protein-1 (MCP-1) expression in human articular cartilage. Induction by peptide regulatory factors and differential effects of dexamethasone and retinoic acid.

P M Villiger 1, R Terkeltaub 1, M Lotz 1
PMCID: PMC443125  PMID: 1365641

Abstract

Monocyte influx and activation in synovial joints are important in the pathogenesis of both degenerative and inflammatory arthropathies. In this study, we demonstrate the potential of articular cartilage to directly modulate these events. IL-1-stimulated human articular chondrocytes transcribed 0.7-kb monocyte chemoattractant protein-1 (MCP-1) mRNA. In situ hybridization of cartilage organ cultures revealed MCP-1 transcripts in chondrocytes in the superficial tangential zone within 2 h of stimulation with IL-1. Chondrocytes in deeper layers responded by 4 h and reached maximum MCP-1 mRNA levels by 8-12 h. IL-1-stimulated cartilage organ and chondrocyte monolayer cultures released functional monocyte chemotactic activity. This was neutralized by a monoclonal antibody specific for MCP-1, and was associated with the synthesis and secretion of immunoreactive 13-kD and 15-kD isoforms of MCP-1. Regulators and signal transduction pathways involved with the expression of the MCP-1 gene in chondrocytes were analyzed. Steady-state mRNA levels were increased by the known chondrocyte activators IL-1, tumor necrosis factor alpha, LPS, platelet-derived growth factor, and transforming growth factor beta. In addition, leukemia inhibitory factor induced MCP-1 gene expression and protein synthesis, identifying this cytokine as a new regulator of chondrocyte function. Dexamethasone blunted the induction of MCP-1 gene expression by IL-1 and by activators of protein kinase A as well as protein kinase C signal transduction pathways. In contrast, retinoic acid strongly increased phorbol myristate acetate-induced MCP-1 expression and potentiated the effects of IL-1 and LPS. In conclusion, chondrocytes express MCP-1 in response to factors that are present in cartilage or synovium. This provides a mechanism by which cartilage can play an active role in the initiation and progression of arthritis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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