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- Kurata Tomo
- Dept. Mol. & Cell. Pharmacol., Grad. Sch. Pharmaceut. Sci., Nagoya City Univ.
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- Suzuki Yoshiaki
- Dept. Mol. & Cell. Pharmacol., Grad. Sch. Pharmaceut. Sci., Nagoya City Univ.
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- Tateno Shinya
- Dept. Mol. & Cell. Pharmacol., Grad. Sch. Pharmaceut. Sci., Nagoya City Univ.
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- Miyaki Shigeru
- Dept. Orthopaedic Surg., Grad. Sch. Biomed. & Health Sci., Hiroshima Univ.
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- Elva Bernotiene
- Dept. Regenerative Med., Innov. Med. Ctr.
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- Wayne Giles
- Dept. Physiol. & Pharmacol., Cumming Sch. Med., Calgary Univ.
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- Yamamura Hisao
- Dept. Mol. & Cell. Pharmacol., Grad. Sch. Pharmaceut. Sci., Nagoya City Univ.
Bibliographic Information
- Other Title
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- 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
Abstract
<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>
Journal
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- Proceedings for Annual Meeting of The Japanese Pharmacological Society
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Proceedings for Annual Meeting of The Japanese Pharmacological Society 97 (0), 2-B-SS12-2-, 2023
Japanese Pharmacological Society
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Keywords
Details 詳細情報について
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- CRID
- 1390017267762270208
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- ISSN
- 24354953
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- Text Lang
- ja
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- Data Source
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- JaLC
- Crossref
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- Abstract License Flag
- Disallowed