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博士論文
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DOI[info:doi/10.1186/s12891-019-2609-x]のデータに遷移します
Expression of the RANK/RANKL/OPG system in the human intervertebral disc: implication for the pathogenesis of intervertebral disc degeneration
- 国立国会図書館永続的識別子
- info:ndljp/pid/11671775
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- application/pdfBackground: The expression of the receptor activator of nuclear factor kappa B (RANK) /RANK ligand (RANKL)/osteoprotegerin (OPG) system...
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デジタル
- 資料種別
- 博士論文
- 著者・編者
- Sano, Tomohiko
- 著者標目
- 出版事項
- 出版年月日等
- 2020-09-16
- 出版年(W3CDTF)
- 2020-09-16
- 授与機関名
- 三重大学
- 授与年月日
- 2020-09-16
- 授与年月日(W3CDTF)
- 2020-09-16
- 報告番号
- 甲医学第2034号
- 学位
- 博士(医学)
- 博論授与番号
- 甲医学第2034号
- 本文の言語コード
- eng
- 件名標目
- 対象利用者
- 一般
- 一般注記
- application/pdfBackground: The expression of the receptor activator of nuclear factor kappa B (RANK) /RANK ligand (RANKL)/osteoprotegerin (OPG) system and its association with the progression of intervertebral disc (IVD) degeneration has recently been reported in a human IVD. However, the effect of the RANK/RANKL/OPG system on the matrix metabolism of human IVD cells, especially on the expression of catabolic factors relevant to IVD degeneration, remains unknown. The purpose of this study was to examine the expression of the RANK/RANKL/OPG system, and then to evaluate the effect of this system on the expression of catabolic factors by human IVD cells.Methods: Annulus fibrosus (AF) and nucleus pulposus (NP) cells isolated by sequential enzyme digestion from human IVD tissues obtained during spine surgeries were monolayer cultured. The expression of the RANK/RANKL/OPG system was determined using immunohistochemical methods and real-time polymerase chain reaction (PCR).To evaluate the influence of interleukin-1 beta (IL-1β) stimulation on the mRNA expression of RANK, RANKL, and OPG, recombinant human IL-1β (rhIL-1β) was administered in the culture media of IVD cells. To examine the influence of RANKL signaling on the expression of matrix metalloprotease-3 (MMP-3), MMP-13, and IL-1β, the cells were cultured with exogenous recombinant human RANKL (rhRANKL), recombinant human OPG (rhOPG) or antihuman RANKL mouse monoclonal antibody (ahRANKL-mAB) with or without rhIL-1β.Results: Immunoreactivity to RANK/RANKL/OPG and the mRNA expression of the three genes were obviously identified in both AF and NP cells. rhIL-1β stimulation significantly upregulated the mRNA expression level of RANK/RANKL/OPG. The mRNA expression of catabolic factors was significantly upregulated by stimulation of rhRANKL in the presence of rhIL-1β. On the other hand, the administration of either rhOPG or ahRANKL-mAB significantly suppressed the mRNA expression of catabolic factors that had been upregulated by rhIL-1β stimulation. The suppressive effect of ahRANKL-mAB against rhIL-1β stimulation was also confirmed by the protein expression ofMMP-3.Conclusions: The present study showed that the RANK/RANKL/OPG system may be involved in the progression of IVD degeneration. This study also suggested the potential use of anti-RANKL monoclonal antibody and OPG as therapeutic agents to suppress the progression of IVD degeneration.本文/Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, Mie 514-8507, Japan13p
- DOI
- info:doi/10.1186/s12891-019-2609-x
- 国立国会図書館永続的識別子
- info:ndljp/pid/11671775
- コレクション(共通)
- コレクション(障害者向け資料:レベル1)
- コレクション(個別)
- 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
- 収集根拠
- 博士論文(自動収集)
- 受理日(W3CDTF)
- 2021-05-16T23:51:55+09:00
- 作成日(W3CDTF)
- 2021-01-05
- 記録形式(IMT)
- application/pdf
- オンライン閲覧公開範囲
- 国立国会図書館内限定公開
- デジタル化資料送信
- 図書館・個人送信対象外
- 遠隔複写可否(NDL)
- 可
- 連携機関・データベース
- 国立国会図書館 : 国立国会図書館デジタルコレクション