PMID- 26369531 OWN - NLM STAT- MEDLINE DCOM- 20161028 LR - 20181113 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 411 IP - 1-2 DP - 2016 Jan TI - Activation of canonical Wnt/beta-catenin signaling inhibits H2O2-induced decreases in proliferation and differentiation of human periodontal ligament fibroblasts. PG - 83-94 LID - 10.1007/s11010-015-2570-4 [doi] AB - 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/beta-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 beta-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 muM 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/beta-catenin pathway improves proliferation and mineralization in H2O2-exposed hPLFs by downregulating Nrf2. FAU - Kook, Sung-Ho AU - Kook SH AD - Cluster for Craniofacial Development & Regeneration Research, Chonbuk National University, Jeonju, 561-756, South Korea. AD - Department of Bioactive Material Sciences, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju, 561-756, South Korea. FAU - Lee, Daewoo AU - Lee D AD - Department of Bioactive Material Sciences, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju, 561-756, South Korea. FAU - Cho, Eui-Sic AU - Cho ES AD - Cluster for Craniofacial Development & Regeneration Research, Chonbuk National University, Jeonju, 561-756, South Korea. AD - Department of Bioactive Material Sciences, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju, 561-756, South Korea. FAU - Heo, Jung Sun AU - Heo JS AD - Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, South Korea. FAU - Poudel, Sher Bahadur AU - Poudel SB AD - Cluster for Craniofacial Development & Regeneration Research, Chonbuk National University, Jeonju, 561-756, South Korea. AD - Department of Bioactive Material Sciences, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju, 561-756, South Korea. FAU - Ahn, Yu-Hyeon AU - Ahn YH AD - Cluster for Craniofacial Development & Regeneration Research, Chonbuk National University, Jeonju, 561-756, South Korea. AD - Department of Bioactive Material Sciences, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju, 561-756, South Korea. FAU - Hwang, Jae-Won AU - Hwang JW AD - Cluster for Craniofacial Development & Regeneration Research, Chonbuk National University, Jeonju, 561-756, South Korea. AD - Department of Bioactive Material Sciences, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju, 561-756, South Korea. FAU - Ji, Hyeok AU - Ji H AD - Department of Bioactive Material Sciences, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju, 561-756, South Korea. FAU - Kim, Jong-Ghee AU - Kim JG AD - Department of Bioactive Material Sciences, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju, 561-756, South Korea. FAU - Lee, Jeong-Chae AU - Lee JC AD - Cluster for Craniofacial Development & Regeneration Research, Chonbuk National University, Jeonju, 561-756, South Korea. leejc88@jbnu.ac.kr. AD - Department of Bioactive Material Sciences, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju, 561-756, South Korea. leejc88@jbnu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150914 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Wnt Proteins) RN - 0 (beta Catenin) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Adult MH - Alkaline Phosphatase/metabolism MH - Cell Differentiation/*drug effects MH - Cell Proliferation/*drug effects MH - Fibroblasts/cytology/drug effects MH - Humans MH - Hydrogen Peroxide/*pharmacology MH - Male MH - Periodontal Ligament/cytology/*drug effects/enzymology MH - *Signal Transduction MH - Wnt Proteins/*metabolism MH - Young Adult MH - beta Catenin/genetics/*metabolism OTO - NOTNLM OT - Differentiation OT - Human periodontal ligament fibroblasts OT - Hydrogen peroxide OT - Nrf2 OT - Wnt pathway EDAT- 2015/09/16 06:00 MHDA- 2016/11/01 06:00 CRDT- 2015/09/16 06:00 PHST- 2015/05/20 00:00 [received] PHST- 2015/09/04 00:00 [accepted] PHST- 2015/09/16 06:00 [entrez] PHST- 2015/09/16 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] AID - 10.1007/s11010-015-2570-4 [pii] AID - 10.1007/s11010-015-2570-4 [doi] PST - ppublish SO - Mol Cell Biochem. 2016 Jan;411(1-2):83-94. doi: 10.1007/s11010-015-2570-4. Epub 2015 Sep 14.