title: A suppressive effect of prostaglandin E2on the expression ofSERPINE1/plasminogen activator inhibitor-1 in human articular chondrocytes: Anin vitropilot study.
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 PGE2suppressed the expression ofSERPINE1/plasminogen activator inhibitor (PAI)-1 mRNA in chondrocytes, we focused on the effect of PGE2on 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 culturedin vitroas 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 thein vitroPGE2stimulation 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 PGE2induced 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.
authors: Department of Biochemistry.
authors: Kayo
authors: K
authors: Masuko
authors: Department of Frontier Medicine, Institute of Medical Science.
authors: Minako
authors: M
authors: Murata
authors: Department of Biochemistry.
authors: Naoya
authors: N
authors: Suematsu
authors: Department of Biochemistry.
authors: Kazuki
authors: K
authors: Okamoto
authors: Department of Frontier Medicine, Institute of Medical Science.
authors: Kazuo
authors: K
authors: Yudoh
authors: Department of Orthopedic Surgery, St. Marianna University School of Medicine, Kawasaki-shi, Kanagawa, Japan.
authors: Hiroyuki
authors: H
authors: Shimizu
authors: Department of Orthopedic Surgery, St. Marianna University School of Medicine, Kawasaki-shi, Kanagawa, Japan.
authors: Moroe
authors: M
authors: Beppu
authors: Department of Joint Disease and Rheumatism, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Nakamura
authors: Department of Biochemistry.
authors: Tomohiro
authors: T
authors: Kato
keywords: PAI-1; PGE2; chondrocyte; prostaglandin