ID | 113368 |
Title Alternative | 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
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Author |
Hutami, Islamy Rahma
Tokushima University
Mino-Oka, Akiko
Tokushima University
Shinohara, Takehiro
Tokushima University
Tanaka, Eiji
Tokushima University
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Keywords | FAS
S1P1
OSTEOCLAST
TEMPOROMANDIBULAR JOINT
SN50
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Content Type |
Thesis or Dissertation
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Description | 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.
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Journal Title |
Biochemical and Biophysical Research Communications
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ISSN | 0006291X
10902104
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NCID | AA00564395
AA11542044
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Publisher | Elsevier Inc.
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Volume | 490
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Issue | 4
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Start Page | 1274
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End Page | 1281
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Published Date | 2017-07-04
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Remark | 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 | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3279号
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Diploma Number | 甲口第444号
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Granted Date | 2019-03-22
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Degree Name |
Doctor of Dental Science
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Grantor |
Tokushima University
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departments |
Oral Sciences
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