RRC ID |
44810
|
著者 |
Hiyama T, Ozeki N, Mogi M, Yamaguchi H, Kawai R, Nakata K, Kondo A, Nakamura H.
|
タイトル |
Matrix metalloproteinase-3 in odontoblastic cells derived from ips cells: unique proliferation response as odontoblastic cells derived from ES cells.
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ジャーナル |
PLoS One
|
Abstract |
We previously reported that matrix metalloproteinase (MMP)-3 accelerates wound healing following dental pulp injury. In addition, we reported that a proinflammatory cytokine mixture (tumor necrosis factor-α, interleukin (IL)-1β and interferon-γ) induced MMP-3 activity in odontoblast-like cells derived from mouse embryonic stem (ES) cells, suggesting that MMP-3 plays a potential unique physiological role in wound healing and regeneration of dental pulp in odontoblast-like cells. In this study, we tested the hypothesis that upregulation of MMP-3 activity by IL-1β promotes proliferation and apoptosis of purified odontoblast-like cells derived from induced pluripotent stem (iPS) and ES cells. Each odontoblast-like cell was isolated and incubated with different concentrations of IL-1β. MMP-3 mRNA and protein expression were assessed using RT-PCR and western blotting, respectively. MMP-3 activity was measured using immunoprecipitation and a fluorescence substrate. Cell proliferation and apoptosis were determined using ELISA for BrdU and DNA fragmentation, respectively. siRNA was used to reduce MMP-3 transcripts in these cells. Treatment with IL-1β increased MMP-3 mRNA and protein levels, and MMP-3 activity in odontoblast-like cells. Cell proliferation was found to markedly increase with no changes in apoptosis. Endogenous tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were constitutively expressed during all experiments. The exocytosis inhibitor, Exo1, potently suppressed the appearance of MMP-3 in the conditioned medium. Treatment with siRNA against MMP-3 suppressed an IL-1β-induced increase in MMP-3 expression and activity, and also suppressed cell proliferation, but unexpectedly increased apoptosis in these cells (P<0.05). Exogenous MMP-3 was found to induce cell proliferation in odontoblast-like cells derived from iPS cells and ES cells. This siRNA-mediated increase in apoptosis could be reversed with exogenous MMP-3 stimulation (P<0.05). Taken together, IL-1β induced MMP-3-regulated cell proliferation and suppressed apoptosis in odontoblast-like cells derived from iPS and ES cells.
|
巻・号 |
8(12)
|
ページ |
e83563
|
公開日 |
2013-1-1
|
DOI |
10.1371/journal.pone.0083563
|
PII |
PONE-D-13-41129
|
PMID |
24358294
|
PMC |
PMC3865184
|
MeSH |
Animals
Cell Differentiation / drug effects
Cell Differentiation / genetics
Cell Proliferation* / drug effects
Cells, Cultured
Culture Media, Conditioned / pharmacology
Embryonic Stem Cells / drug effects
Embryonic Stem Cells / physiology*
Gene Expression / drug effects
Induced Pluripotent Stem Cells / drug effects
Induced Pluripotent Stem Cells / physiology*
Interleukin-1beta / pharmacology
Matrix Metalloproteinase 3 / genetics*
Matrix Metalloproteinase 3 / metabolism
Mice
Mice, Inbred C57BL
Odontoblasts / drug effects
Odontoblasts / physiology*
|
IF |
2.74
|
引用数 |
18
|
WOS 分野
|
DENTISTRY, ORAL SURGERY & MEDICINE
|
リソース情報 |
ヒト・動物細胞 |
B6G-2(AES0003) |