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Chemokines differentially induce matrix metalloproteinase-3 and prostaglandin E₂ in human articular chondrocytes

K. Masuko-Hongo, T. Sato, K. Nishioka

Department of Bioregulation, Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan.\

ABSTRACT
Objective
To explore prostaglandin (PG) E₂ production by human articular chondrocytes induced by different chemokines.

Methods
Human chondrocytes were enzymatically isolated from the articular cartilage of patients with rheumatoid arthritis (RA), osteoarthritis (OA) or traumatic fracture (N) who underwent total joint replacement. They were cultured in vitro as monolayers and then exposed to MCP-1, RANTES or SDF-1 for 24 h. Levels of PGE₂ and MMP-3 in the culture supernatant were then immunoassayed.

Results
PGE₂ production was enhanced up to 2.7-fold in a subset of samples. Responses to different chemokines were heterogeneous even within the same disease groups. As previously reported, chemokines induced MMP-3 secretion by chondrocytes, but there was no significant correlation between levels of PGE₂ and MMP-3.

Conclusion
We here document the presence of "responders" among OA, RA and normal chondrocytes that produce enhanced levels of PGE₂ upon stimulation by chemokines. The relationship between chemokines and prostaglandins could differentially influence the pathogenic network responsible for cartilage degradation in arthropathy.

Key words
Chemokine, chondrocytes, prostaglandin, MMP.

This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Ministry of Health, Labour and Welfare of Japan, and the Japan Rheumatism Foundation.
Please address correspondence and re-print requests to: Kayo Masuko-Hongo, MD, Department of Bioregulation, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216-8512 Japan.
E-mail: khongo@marianna-u.ac.jp