ID | 62299 |
フルテキストURL | |
著者 |
Takeshita, Ayumu
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nishida, Keiichiro
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
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Yoshida, Aki
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nasu, Yoshihisa
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nakahara, Ryuichi
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaneda, Daisuke
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ohashi, Hideki
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ozaki, Toshifumi
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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抄録 | We investigated the expression and localization of the receptor activator nuclear factor kappa B ligand (RANKL) in cartilage from patients with rheumatoid arthritis (RA) of relevance to cartilage degeneration. We also examined the role of exogenous lymphotoxin (LT)-alpha on RANKL expression in human chondrocytes and its effect on in vitro osteoclast differentiation. Cartilage and synovial fluid samples were obtained from 45 patients undergoing total joint replacement surgery or joint puncture, including 24 patients with osteoarthritis (OA) and 21 patients with RA. RANKL expression in articular cartilage was examined by immunohistochemistry. LT-alpha concentrations in synovial fluid were measured using an enzyme-linked immunosorbent assay (ELISA). Normal human chondrocytes were stimulated with LT-alpha, and the relative mRNA levels of RANKL, osteoprotegerin (OPG), matrix metalloproteinase-9, and vascular endothelial growth factor were examined by real-time polymerase chain reaction. Soluble RANKL protein in culture media was measured using ELISA, and membrane-bound RANKL protein in cells was examined by western blotting. Co-cultures of human chondrocytes with peripheral blood mononuclear cells (PBMCs) were stimulated with macrophage-colony stimulating factor and LT-alpha, and osteoclast differentiation was evaluated by staining for tartrate-resistant acid phosphatase. LT-alpha concentrations were higher in RA synovial fluid than in OA samples. The population of RANKL-positive chondrocytes of RA cartilage was higher than that of OA cartilage, and correlated with cartilage degeneration. Stimulation of cultured human chondrocytes by LT-alpha increased RANKL expression, the RANKL/OPG ratio, and angiogenic factors. Membrane-bound RANKL in chondrocytes was up-regulated after stimulation of LT-alpha, whereas soluble RANKL in culture medium did not increase. Co-cultures of human chondrocytes and PBMCs demonstrated that LT-alpha stimulated human chondrocytes to produce RANKL and induced osteoclastic differentiation of PBMCs. RANKL produced by chondrocytes may contribute to cartilage destruction during RA and LT-alpha could promote the expression of RANKL in human chondrocytes.
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発行日 | 2021-07-07
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出版物タイトル |
PLOS ONE
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巻 | 16巻
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号 | 7号
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出版者 | Public Library Science
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開始ページ | e0254268
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ISSN | 1932-6203
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2021 Takeshita et al.
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1371/journal.pone.0254268
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ライセンス | https://creativecommons.org/licenses/by/4.0/
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助成機関名 |
Chugai Pharmaceutical CO., Ltd.
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助成番号 | AC-1-20160425175630-254002
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