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. 2016 Jan;411(1-2):83-94.
doi: 10.1007/s11010-015-2570-4. Epub 2015 Sep 14.

Activation of canonical Wnt/β-catenin signaling inhibits H2O2-induced decreases in proliferation and differentiation of human periodontal ligament fibroblasts

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  4   5
Affiliations

Activation of canonical Wnt/β-catenin signaling inhibits H2O2-induced decreases in proliferation and differentiation of human periodontal ligament fibroblasts

Sung-Ho Kook et al. Mol Cell Biochem. 2016 Jan.

Abstract

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: Differentiation; Human periodontal ligament fibroblasts; Hydrogen peroxide; Nrf2; Wnt pathway.

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