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Activation of canonical Wnt/β-catenin signaling inhibits H2O2-induced decreases in proliferation and differentiation of human periodontal ligament fibroblasts
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  • 作者:Sung-Ho Kook ; Daewoo Lee ; Eui-Sic Cho ; Jung Sun Heo…
  • 关键词:Human periodontal ligament fibroblasts ; Hydrogen peroxide ; Wnt pathway ; Differentiation ; Nrf2
  • 刊名:Molecular and Cellular Biochemistry
  • 出版年:2016
  • 出版时间:January 2016
  • 年:2016
  • 卷:411
  • 期:1-2
  • 页码:83-94
  • 全文大小:2,686 KB
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  • 作者单位:Sung-Ho Kook (1) (2)
    Daewoo Lee (2)
    Eui-Sic Cho (1) (2)
    Jung Sun Heo (3)
    Sher Bahadur Poudel (1) (2)
    Yu-Hyeon Ahn (1) (2)
    Jae-Won Hwang (1) (2)
    Hyeok Ji (2)
    Jong-Ghee Kim (2)
    Jeong-Chae Lee (1) (2)

    1. Cluster for Craniofacial Development & Regeneration Research, Chonbuk National University, Jeonju, 561-756, South Korea
    2. Department of Bioactive Material Sciences, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju, 561-756, South Korea
    3. Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, South Korea
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Life Sciences
    Biochemistry
    Medical Biochemistry
    Oncology
    Cardiology
  • 出版者:Springer Netherlands
  • ISSN:1573-4919
文摘
Human periodontal ligament fibroblasts (hPLFs) are exposed to oxidative stress during periodontal inflammation and dental treatments. It is hypothesized that hydrogen peroxide (H2O2)-mediated oxidative stress decreases survival and osteogenic differentiation of hPLFs, whereas these decreases are prevented by activation of the Wnt pathway. However, there has been a lack of reports that define the exact roles of canonical Wnt/β-catenin signaling in H2O2-exposed hPLFs. Treatment with H2O2 reduced viability and proliferation in hPLFs in a dose- and time-dependent manner and led to mitochondria-mediated apoptosis. Pretreatment with lithium chloride (LiCl) or Wnt1 inhibited the oxidative damage that occurred in H2O2-exposed hPLFs. However, knockout of β-catenin or treatment with DKK1 facilitated the H2O2-induced decreases in viability, mitochondrial membrane potential, and Bcl-2 induction. Osteoblastic differentiation of hPLFs was also inhibited by combined treatment with 100 μM H2O2, as evidenced by the decreases in alkaline phosphatase (ALP) activity and mineralization. H2O2-mediated inhibition of osteoblast differentiation in hPLFs was significantly attenuated in the presence of 500 ng/ml Wnt1 or 20 mM LiCl. In particular, H2O2 stimulated the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) at protein and mRNA levels in hPLFs, whereas the induction was almost completely suppressed in the presence of Wnt1 or LiCl. Furthermore, siRNA-mediated silencing of Nrf2 blocked H2O2-induced decreases in ALP activity and mineralization of hPLFs with the concomitant restoration of runt-related transcription factor 2 and osteocalcin mRNA expression and ALP activity. Collectively, these results suggest that activation of the Wnt/β-catenin pathway improves proliferation and mineralization in H2O2-exposed hPLFs by downregulating Nrf2. Keywords Human periodontal ligament fibroblasts Hydrogen peroxide Wnt pathway Differentiation Nrf2

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