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