変形性膝関節症の軟骨細胞におけるKv1.6チャネルの役割

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  • 倉田 朋
    名古屋市立大・院薬・細胞分子薬効解析学
  • 鈴木 良明
    名古屋市立大・院薬・細胞分子薬効解析学
  • 楯野 真也
    名古屋市立大・院薬・細胞分子薬効解析学
  • 味八木 茂
    広島大・院医・整形外科学
  • Elva Bernotiene
    Department of Regenerative Medicine・Innovative Medicine Center
  • Wayne Giles
    Department of Physiology & Pharmacology・Cumming School of Medicine・University of Calgary
  • 山村 寿男
    名古屋市立大・院薬・細胞分子薬効解析学

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タイトル別名
  • Role of Kv1.6 channel in chondrocytes in osteoarthritis

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<p>Osteoarthritis (OA) is a chronic inflammatory disease characterized by a decrease in cartilage matrix, disorders of joint movement, and severe pain. Previous studies have suggested that an increase in intracellular Ca2+ concentration ([Ca2+]­i) in chondrocytes is associated with OA progression. However, the mechanism underlying this increased [Ca2+]i  is unknown. In the present study, we aimed to elucidate this mechanism and its roles in OA progression. Primary chondrocytes were isolated from C57BL/6 mice, and treated with interleukin (IL)-1β, a major cytokine secreted into synovial fluid during OA. In IL-1β-treated chondrocytes, resting membrane potential was depolarized, and resting [Ca2+]i was increased due to the downregulation of voltage-gated K+ channel, Kv1.6. This downregulation of Kv1.6 was also detected in chondrocytes from OA model mice and OA patients. IL-1β induced depolarization of mitochondrial membrane potential (ΔΨm) and cell death. In contrast, overexpression of Kv1.6 in chondrocytes using adenovirus reduced resting [Ca2+]­i, increased ΔΨm, and inhibited cell death. In summary, IL-1β downregulates Kv1.6 and increases resting [Ca2+]­i, resulting in mitochondrial Ca2+ overload and subsequent cell death. Our findings may contribute to the understanding of OA pathogenesis and the development of new treatments for OA.</p>

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