Browsing by Author "Gwan Shik Kim"

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    EGF Inhibits Wnt/β-Catenin-Induced Osteoblast Differentiation by Promoting β-Catenin Degradation
    (2015-12-01) Kanitsak Boonanantanasarn; Hye Lim Lee; Kyunghwa Baek; Kyung Mi Woo; Hyun Mo Ryoo; Jeong Hwa Baek; Gwan Shik Kim; Seoul National University; Mahidol University; University of California, Los Angeles; Gangneung-Wonju National University
    © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc. Bone morphogenetic protein (BMP) and canonical Wnts are representative developmental signals that enhance osteoblast differentiation and bone formation. Previously, we demonstrated that epidermal growth factor (EGF) inhibits BMP2-induced osteoblast differentiation by inducing Smurf1 expression. However, the regulatory role of EGF in Wnt/β-catenin-induced osteoblast differentiation has not been elucidated. In this study, we investigated the effect of EGF on Wnt/β-catenin signaling-induced osteoblast differentiation using the C2C12 cell line. EGF significantly suppressed the expression of osteoblast marker genes, which were induced by Wnt3a and a GSK-3β inhibitor. EGF increased the expression levels of Smurf1 mRNA and protein. Smurf1 knockdown rescued Wnt/β-catenin-induced osteogenic marker gene expression in the presence of EGF. EGF treatment or Smurf1 overexpression did not affect β-catenin mRNA expression levels, but reduced β-catenin protein levels and TOP-Flash activity. EGF and Smurf1 promoted β-catenin ubiquitination. Co-immunoprecipitation and GST pull-down assays showed that Smurf1 associates with β-catenin. These results suggest that EGF/Smurf1 inhibits Wnt/β-catenin-induced osteogenic differentiation and that Smurf1 downregulates Wnt/β-catenin signaling by enhancing proteasomal degradation of β-catenin. J. Cell. Biochem. 116: 2849-2857, 2015.
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    Erratum to Hyperglycemia increases the expression levels of sclerostin in a reactive oxygen species- and tumor necrosis factor-alpha-dependent manner [J Periodontal Implant Sci, 45, (2015), 101-110] DOI:10.5051/jpis.2015.45.3.101
    (2015-01-01) Jiho Kang; Kanitsak Boonanantanasarn; Kyunghwa Baek; Kyung Mi Woo; Hyun Mo Ryoo; Jeong Hwa Baek; Gwan Shik Kim; Seoul National University; Mahidol University; Gangneung-Wonju National University College of Dentistry
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    Hyperglycemia increases the expression levels of sclerostin in a reactive oxygen species- and tumor necrosis factor-alpha-dependent manner
    (2015-01-01) Jiho Kang; Kanitsak Boonanantanasarn; Kyunghwa Baek; Kyung Mi Woo; Hyun Mo Ryoo; Jeong Hwa Baek; Gwan Shik Kim; Seoul National University; Mahidol University; Gangneung-Wonju National University
    © 2015 Korean Academy of Periodontology. Purpose: Sclerostin, an inhibitor of Wnt/β-catenin signaling, exerts negative effects on bone formation and contributes to periodontitis-induced alveolar bone loss. Recent studies have demonstrated that serum sclerostin levels are increased in diabetic patients and that sclerostin expression in alveolar bone is enhanced in a diabetic periodontitis model. However, the molecular mechanism of how sclerostin expression is enhanced in diabetic patients remains elusive. Therefore, in this study, the effect of hyperglycemia on the expression of sclerostin in osteoblast lineage cells was examined. Methods: C2C12 and MLO-Y4 cells were used in this study. In order to examine the effect of hyperglycemia, the glucose concentration in the culture medium was adjusted to a range of levels between 40 and 100 mM. Gene expression levels were examined by quantitative reverse transcription-polymerase chain reaction and Western blot assays. Top-Flash reporter was used to examine the transcriptional activity of the β-catenin/lymphoid enhanced factor/T-cell factor complex. Tumor necrosis factor-alpha (TNFα) protein levels were examined with the enzyme-linked immunosorbent assay. The effect of reactive oxygen species on sclerostin expression was examined by treating cells with 1 mM H2O2 or 20 mM N-acetylcysteine. Results: The high glucose treatment increased the mRNA and protein levels of sclerostin. High glucose suppressed Wnt3a-induced Top-Flash reporter activity and the expression levels of osteoblast marker genes. High glucose increased reactive oxygen species production and TNFα expression levels. Treatment of cells with H2O2 also enhanced the expression levels of TNFα and sclerostin. In addition, N-acetylcysteine treatment or knockdown of TNFα attenuated high glucose-induced sclerostin expression. Conclusions: These results suggest that hyperglycemia increases sclerostin expression via the enhanced production of reactive oxygen species and TNFα.