title: The DNA repair enzyme apurinic/apyrimidinic endonuclease (Apex nuclease) 2 has the potential to protect against down-regulation of chondrocyte activity in osteoarthritis.
abstract: Apurinic/apyrimidinic endonuclease 2 (Apex 2) plays a critical role in DNA repair caused by oxidative damage in a variety of human somatic cells. We speculated that chondrocyte Apex 2 may protect against the catabolic process of articular cartilage in osteoarthritis (OA). Higher levels of Apex 2 expression were histologically observed in severely compared with mildly degenerated OA cartilage from STR/OrtCrlj mice, an experimental model which spontaneously develops OA. The immunopositivity of Apex 2 was significantly correlated with the degree of cartilage degeneration. Moreover, the OA-related catabolic factor interleukin-1β induced the expression of Apex 2 in chondrocytes, while Apex 2 silencing using small interfering RNA reduced chondrocyte activity in vitro. The expression of Apex 2 in chondrocytes therefore appears to be associated with the degeneration of articular cartilage and could be induced by an OA-related catabolic factor to protect against the catabolic process of articular cartilage. Our findings suggest that Apex 2 may have the potential to prevent the catabolic stress-mediated down-regulation of chondrocyte activity in OA.
authors.affiliation: Department of Sports Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. aburainisuke@marianna-u.ac.jp.
authors.forename: Naoko
authors.initials: N
authors.lastname: Yui
authors.affiliation: Department of Sports Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. h2yoshioka@marianna-u.ac.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Yoshioka
authors.affiliation: Department of Sports Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. fujiya-1487@marianna-u.ac.jp.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Fujiya
authors.affiliation: Department of Sports Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. musha@marianna-u.ac.jp.
authors.forename: Haruki
authors.initials: H
authors.lastname: Musha
authors.affiliation: Department of Orthopedic Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. mbortho7@marianna-u.ac.jp.
authors.forename: Moroe
authors.initials: M
authors.lastname: Beppu
authors.affiliation: Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. r2karasawa@marianna-u.ac.jp.
authors.forename: Rie
authors.initials: R
authors.lastname: Karasawa
authors.affiliation: Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. yudo@marianna-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yudoh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D015536:Down-Regulation; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D064251:Multifunctional Enzymes; D010003:Osteoarthritis / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D064251:Multifunctional Enzymes; C476886:Apex2 protein, mouse; D004720:Endonucleases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase