Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Change in the Levels of Intracellular Antioxidants during Aging of Articular Chondrocytes and Cartilage

연골세포 및 관절연골의 노화 과정에서 세포내 항산화 인자들의 변화

  • Kim, Kang Mi (Department of Microbiology & Immunology, Pusan National University College of Medicine) ;
  • Kim, Yoon Jae (Department of Anatomy & Cell Biology, Dong-A University College of Medicine) ;
  • Kim, Jong Min (Department of Anatomy & Cell Biology, Dong-A University College of Medicine) ;
  • Sohn, Dong Hyun (Department of Microbiology & Immunology, Pusan National University College of Medicine) ;
  • Park, Young Chul (Department of Microbiology & Immunology, Pusan National University College of Medicine)
  • 김강미 (부산대학교 의과대학 미생물학 및 면역학교실) ;
  • 김윤재 (동아대학교 의과대학 해부학 및 세포생물학교실) ;
  • 김종민 (동아대학교 의과대학 해부학 및 세포생물학교실) ;
  • 손동현 (부산대학교 의과대학 미생물학 및 면역학교실) ;
  • 박영철 (부산대학교 의과대학 미생물학 및 면역학교실)
  • Received : 2019.05.20
  • Accepted : 2019.08.07
  • Published : 2019.08.30
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Abstract

Cartilage diseases, such as rheumatoid arthritis (RA) and osteoarthritis (OA), are associated with the loss of chondrocytes and degradation of articular cartilage. Recent studies revealed that inflammatory reactive oxygen species (ROS) and age-related oxidative stress can affect chondrocyte activity and cartilage homeostasis. We investigated changes in the levels of intracellular antioxidants during cellular senescence of primary chondrocytes from rat articular cartilages. Cellular senescence was induced by serial subculture (passages 0, 2, 4, and 8) of chondrocytes and measured using specific senescence-associated ${\beta}$-galactosidase ($SA-{\beta}-gal$) staining. ROS production increased significantly in the senescent chondrocytes. In addition, total glutathione (GSSG/GSH) and superoxide dismutase (SOD) levels and heme oxygenase-1 (HO-1) expression increased in senescent chondrocytes induced by serial subculture. Analysis of changes in intracellular antioxidant levels in articular cartilage from rats of different ages (5, 25, 40, and 72 wk) revealed that total glutathione levels were highest after 40 wk and slightly decreased after 72 wk as compared with those after 25 wk. SOD and HO-1 expression levels increased in accordance with age. Based on these results, we conclude that intracellular antioxidants may be associated with cartilage protection against excessive oxidative stress in the process of chondrocyte senescence and age-related cartilage degeneration in an animal model.

류마티스관절염(rheumatoid arthritis)과 골관절염(osteoarthritis) 같은 관절질환은 연골세포(chondrocytes) 감소와 관절연골(articular cartilage)의 분해를 수반한다. 최근, 연골세포의 활성과 연골 항상성(cartilage homeostasis)에 염증성 ROS (reactive oxygen species) burst 및 나이와 관련된 산화적 스트레스(oxidative stress)의 증가와 관련된 연구가 활발히 진행되고 있다. 본 연구는 관절연골로부터 분리한 연골세포의 노화 과정과 나이대별 관절연골에서 항산화 인자들(antioxidants)의 변화를 조사함으로써, 연골세포와 관절연골의 노화 과정 동안 산화적 스트레스로부터 조직을 보호하는 항산화 인자들의 역할을 규명하는데 목적이 있다. 쥐의 관절연골로부터 분리한 연골세포의 연속 계대배양을 통한 노화 과정에서 산화적 스트레스가 증가함을 관찰하였다. 그리고, 노화 유도한 연골세포는 세포내 총 glutathione (GSSG/GSH) 양과 항산화 효소 superoxide dismutase (SOD)와 heme oxygenase-1 (HO-1)의 발현이 증가하였다. 다음으로, 나이대별 쥐로부터 분리한 관절연골에서 항산화 인자의 발현을 분석하였다. 항산화 인자 glutathione의 양은 40주령에서 발현이 가장 높게 관찰되었으며 72주령에 다소 감소하였고, SOD와 HO-1의 발현은 나이대별로 현저히 증가되는 경향을 보였다. 이를 종합해 볼 때, 세포내 항산화 인자들은 과도한 양의 ROS에 반응하여 연골세포의 노화와 나이와 관련된 관절연골의 퇴화 과정에서 중요한 역할을 하는 것으로 보인다.

Keywords

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