ID 113368
タイトル別表記
破骨細胞におけるNF-κB活性化によるFas / S1P1クロストークがマウスTMJ関節炎の骨リモデリングを制御する
著者
フタミ, イスラミ ラフマ 徳島大学大学院口腔科学教育部(口腔科学専攻)
三野, 彰子 Tokushima University
篠原, 丈裕 Tokushima University
キーワード
FAS
S1P1
OSTEOCLAST
TEMPOROMANDIBULAR JOINT
SN50
資料タイプ
学位論文
抄録
Enhanced turnover of subchondral trabecular bone is a hallmark of rheumatoid arthritis (RA) and it results from an imbalance between bone resorption and bone formation activities. To investigate the formation and activation of osteoclasts which mediate bone resorption, a Fas-deficient MRL/lpr mouse model which spontaneously develops autoimmune arthritis and exhibits decreased bone mass was studied. Various assays were performed on subchondral trabecular bone of the temporomandibular joint (TMJ) from MRL/lpr mice and MRL+/+ mice. Initially, greater osteoclast production was observed in vitro from bone marrow macrophages obtained from MRL/lpr mice due to enhanced phosphorylation of NF-kB, as well as Akt and MAPK, to receptor activator of nuclear factor-kB ligand (RANKL). Expression of sphingosine 1-phosphate receptor 1 (S1P1) was also significantly upregulated in the condylar cartilage. S1P1 was found to be required for S1P-induced migration of osteoclast precursor cells and downstream signaling via Rac1. When SN50, a synthetic NF-kB-inhibitory peptide, was applied to the MRL/lpr mice, subchondral trabecular bone loss was reduced and both production of osteoclastogenesis markers and sphingosine kinase (Sphk) 1/S1P1 signaling were reduced. Thus, the present results suggest that Fas/S1P1 signaling via activation of NF-kB in osteoclast precursor cells is a key factor in the pathogenesis of RA in the TMJ.
掲載誌名
Biochemical and Biophysical Research Communications
ISSN
0006291X
10902104
cat書誌ID
AA00564395
AA11542044
出版者
Elsevier Inc.
490
4
開始ページ
1274
終了ページ
1281
発行日
2017-07-04
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Islamy Rahma Hutamiの学位論文として提出され,学位審査・授与の対象となっている。
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3279号
学位記番号
甲口第444号
学位授与年月日
2019-03-22
学位名
博士(歯学)
学位授与機関
徳島大学
部局
歯学系