A suppressive effect of prostaglandin E₂ on the expression of SERPINE1/plasminogen activator inhibitor-1 in human articular chondrocytes: An in vitro pilot study

Original Research

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Authors: Kayo Masuko, Minako Murata, Naoya Suematsu, Kazuki Okamoto, et al.

Published Date April 2009 Volume 2009:1 Pages 9 - 15

DOI: http://dx.doi.org/10.2147/OARRR.S5508

Kayo Masuko¹, Minako Murata², Naoya Suematsu¹, Kazuki Okamoto¹, Kazuo Yudoh², Hiroyuki Shimizu³, Moroe Beppu³, Hiroshi Nakamura⁴, Tomohiro Kato¹

¹Department of Biochemistry; ²Department of Frontier Medicine, Institute of Medical Science; ³Department of Orthopedic Surgery, St. Marianna University School of Medicine, Kawasaki-shi, Kanagawa, Japan; ⁴Department of Joint Disease and Rheumatism, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

Abstract: Prostaglandin E₂ (PGE₂) is expressed in articular joints with inflammatory arthropathy and may exert catabolic effects leading to cartilage degradation. As we observed in a preliminary experiment that PGE₂ suppressed the expression of SERPINE1/plasminogen activator inhibitor (PAI)-1 mRNA in chondrocytes, we focused on the effect of PGE₂ on PAI-1 in a panel of cultured chondrocytes obtained from osteoarthritic patients. Specifically, articular cartilage specimens were obtained from patients with osteoarthritis who underwent joint surgery. Isolated chondrocytes were cultured in vitro as a monolayer and stimulated with PGE₂. Stimulated cells and culture supernatants were analyzed using Western blotting and enzyme-linked immunosorbent assay. The results confirmed that the in vitro PGE₂ stimulation suppressed the expression of PAI-1 in the tested chondrocyte samples. The inhibitory effect was partly abrogated by an antagonist of EP4 receptor of PGE₂, but not by an EP2 antagonist. Although PGE₂ induced activations of mitogen-activated protein kinases (MAPK), blocking of the MAPK did not abrogate the suppressive effect of PGE₂, implying a distinct signaling pathway. In summary, prostaglandin is suggested to modulate the plasminogen system in chondrocytes. Further elucidation of the interaction might open a new avenue to understand the degradative process of cartilage.

Keywords: chondrocyte, prostaglandin, PGE₂, PAI-1

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