【博士論文】学術データベース

博士論文 / RANK/RANKL/OPG system in the intervertebral disc

著者

書誌事項

タイトル

RANK/RANKL/OPG system in the intervertebral disc

著者名

Takegami Norihiko

学位授与大学

三重大学 (大学ID:0046) (CAT機関ID:KI000538)

取得学位

博士(医学)

学位授与番号

甲医学第1871号

学位授与年月日

2017-12-20

注記・抄録

Background: The receptor activator of NF-κB ligand (RANKL), a member of the TNF ligand superfamily, is known to regulate bone metabolism. The expression of each component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral disc (IVD) has not been examined in detail. The purposes of this study were to examine the expression of the RANK/RANKL/OPG system and to evaluate the function of RANKL in the matrix metabolism of the rat IVD. Methods: Sprague-Dawley, 12-week-old, male rats were used in this study. Anulus fibrosus (AF), nucleus pulposus (NP) and cartilaginous endplate (CEP) cells isolated from dissected thoracolumbar discs were monolayer-cultured. RANK/ RANKL/OPG expression in rat IVDs was examined using real-time polymerase chain reaction (PCR) and immunohistochemical analysis (cultured cells and IVD tissues). To examine the effect of interleukin-1β (IL-1β) stimulation on the mRNA levels of RANK, RANKL and OPG, the cells were cultured with or without recombinant human IL-1β (rhIL-1β). To evaluate the effect of RANKL on the mRNA expression of catabolic factors (IL-1β, matrix metalloproteinase-3 (MMP-3) and MMP-13), the cells were cultured with RANKL in the presence or absence of rhIL-1β. The immunohistochemical expression of this system was also evaluated using human IVD tissues with different grades of degeneration. Results: mRNA expression levels of RANK, RANKL, and OPG were clearly identified in AF, NP and CEP cells. Immunoreactivity to RANK, RANKL and OPG was distributed in the cell membranes and/or cytoplasm of the three types of cells. The mRNA level of RANKL was significantly upregulated by treatment with rhIL-1β of the three types of cells. Treatment with RANKL without rhIL-1β did not induce significant effects on the mRNA expression of catabolic factors by AF, NP and CEP cells. However, the expression was significantly upregulated by stimulation with RANKL in the presence of rhIL-1β. There was a general trend for more RANK/RANKL/OPG-positive cells in human IVD tissues in an advanced stage of degeneration compared to an early stage. Conclusions: Our study showed the possibility that the RANK/RANKL/OPG system may play a part in the process of intervertebral disc degeneration.

本文 / Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

10p

内容の要旨・審査結果の要旨 / 三重大学大学院医学系研究科 生命医科学専攻 病態修復医学講座 運動器外科学分野

キーワード

intervertebral disc, proinflammatory cytokine, Receptor activator of nuclear factor kappa B, Receptor activator of nuclear factor kappa B ligand, Osteoprotegerin, Cartilaginous endplate

各種コード

NII論文ID(NAID)

500001054990

NII著者ID(NRID)
  • 8000001172684
DOI (出版社)

10.1186/s13075-017-1332-y

本文言語コード

eng

データ提供元

機関リポジトリ / NDLデジタルコレクション

博士論文 / 三重大学 / 医学

博士論文 / 三重大学

博士論文 / 医学

関連著者

博士論文 / 大学

博士論文 / 学位