siRNA targeting PLK-1 induces apoptosis of synoviocytes in rheumatoid arthritis.
Polo-like kinase-1 (PLK-1) is a member of the PLK family and participates in the control of cell mitosis. Here, we show that immunoreactive PLK-1 is strongly expressed in synoviocytes and some infiltrative mononuclear cells in synovial tissues from patients with rheumatoid arthritis (RA), while patients with osteoarthritis and injury show little or no expression of PLK-1 in synovial tissues. Western blot analysis shows that PLK is expressed and its expression is enhanced by IL-1beta in RA synoviocytes. IL-1beta also enhanced the cell growth of RA synoviocytes. Moreover, siRNA targeted against PLK-1 significantly decreases the expression of PLK-1 of RA synoviocytes stimulated by IL-1beta and suppresses the proliferation of these synoviocytes through apoptosis. These findings suggest that PLK-1 plays a critical role in the proliferation of RA synoviocytes leading to bone destruction, and siRNA against PLK-1 is potentially useful for the treatment of RA.
Wada
Makoto
M
Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Kawahito
Yutaka
Y
Kimura
Shinya
S
Kohno
Masataka
M
Ishino
Hidetaka
H
Kimura
Mizuho
M
Omoto
Atsushi
A
Yamamoto
Aihiro
A
Hamaguchi
Masahide
M
Tsubouchi
Yasunori
Y
Tokunaga
Daisaku
D
Hojo
Tatsuya
T
Ashihara
Eishi
E
Maekawa
Taira
T
Yoshikawa
Toshikazu
T
D017209:Apoptosis / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D020868:Gene Silencing; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics*; D013582:Synovial Fluid / Q000166:cytology* / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1