Transcriptomics and methylomics in chronic periodontitis with tobacco use: a pilot study

Cho, Young-Dan,Kim, Pil-Jong,Kim, Hong-Gee,Seol, Yang-Jo,Lee, Yong-Moo,Ku, Young,Rhyu, In-Chul,Ryoo, Hyun-Mo BioMed Central 2017 CLINICAL EPIGENETICS Vol.9 No.1

<P><B>Background</B></P><P>Accumulating evidence suggests that tobacco smoking affects the susceptibility to and severity of chronic periodontitis. Epigenetics may explain the role of smoking in the development and progress of periodontal disease. In this study, we performed transcriptomic and methylomic analyses of non-periodontitis and periodontitis-affected gingival tissues according to smoking status.</P><P><B>Methods</B></P><P>Human gingival tissues were obtained from 20 patients, including non-smokers with and without periodontitis (<I>n</I> = 5 per group) and smokers with and without periodontitis (<I>n</I> = 5 per group). Total RNA and genomic DNA were isolated, and their quality was validated according to strict standards. The Illumina NextSeq500 sequencing system was used to generate transcriptome and methylome datasets.</P><P><B>Results</B></P><P>Comprehensive analysis, including between-group correlation, differential gene expression, DNA methylation, gene set enrichment, and protein-protein interaction, indicated that smoking may change the transcription and methylation states of extracellular matrix (ECM) organization-related genes, which exacerbated the periodontal condition.</P><P><B>Conclusions</B></P><P>Our results suggest that smoking-related changes in DNA methylation patterns and subsequent alterations in the expression of genes coding for ECM components may be causally related to the increased susceptibility to periodontitis in smokers as they could influence ECM organization, which in turn may have an effect on disease characteristics.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1186/s13148-017-0381-z) contains supplementary material, which is available to authorized users.</P>

Molecular regulation of matrix extracellular phosphoglycoprotein expression by bone morphogenetic protein-2.

Cho, Young-Dan,Yoon, Won-Joon,Woo, Kyung-Mi,Baek, Jeong-Hwa,Lee, Gene,Cho, Je-Yoel,Ryoo, Hyun-Mo American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.37

<P>Matrix extracellular phosphoglycoprotein (MEPE) is mainly expressed in mineralizing tissues, and its C-terminal proteolytic cleavage product is an acidic-serine-asparate-rich-MEPE-associated motif (ASARM) that is a strong regulator of body phosphate metabolism and mineralization. There is sufficient data supporting a role for MEPE protein function in mineralization, however, little is known about the regulation of MEPE gene expression. As bone morphogenetic protein-2 (BMP-2) is one of the most important signals for calvarial mineralization and MEPE expression is higher in mineralized tissues, we attempted to uncover a regulatory circuit between BMP-2 and MEPE expression. Mepe expression is very low in proliferating MC3T3-E1 cells, but is dramatically increased in the mineralization stage and is strongly stimulated by treatment with BMP-2, even in proliferating cells. Overexpression and knock-down experiments of Smads, Dlx5, and Runx2 indicated that they are indispensable mediators of BMP-2-induced Mepe expression. In contrast, Msx2 showed strong inhibition of Mepe transcription. PHEX is an enzyme that prevents the release of the ASARM motif, a mineralization inhibitor, from the MEPE molecule. Thus, the MEPE/PHEX ratio may be a good indicator of mineralization progression because we found that the mRNA ratio and protein levels were low when osteoblasts were actively differentiating to the mineralization stage and the ratio was high when the cells reached the mineralization stage when it is assumed that osteocytes may protect themselves and make a space to survive from the mineralized matrix by releasing the ASARM motif. Collectively, MEPE expression is bone cell-specific and induced by the BMP-2 signaling pathway. In addition, the MEPE/PHEX ratio of the cell could be a very important barometer indicating the progression of tissue mineralization.</P>

Rescue of a periodontally compromised tooth by non-surgical treatment: a case report

Cho, Young-Dan,Kim, Sungtae,Koo, Ki-Tae,Seol, Yang-Jo,Lee, Yong-Moo,Rhyu, In-Chul,Ku, Young Korean Academy of Periodontology 2016 Journal of Periodontal & Implant Science Vol.46 No.2

Purpose: This article describes a case of the successful non-surgical management of a periodontally compromised maxillary premolar. Methods: A combination therapy, including root planing, occlusal adjustment, and tooth splinting, was applied. Clinical and radiographic examinations were performed during the 16-month follow-up period. Results: All periodontal parameters were improved. There were dramatic decreases (3-6 mm) in the probing pocket depth, tooth mobility, and marginal bone loss. Interestingly, gradual resolution of the periapical radiolucency and alveolar bone regeneration were observed in the radiographs, and the periodontal condition was maintained during the follow-up period. Conclusions: Within the limits of this study, these results demonstrate the importance of natural tooth preservation through proper periodontal treatment and occlusal adjustment of the periodontally compromised tooth, which is typically targeted for tooth extraction and dental implantation.

Epigenetic Modifications and Canonical Wingless/int-1 Class (WNT) Signaling Enable Trans-differentiation of Nonosteogenic Cells into Osteoblasts

Cho, Young-Dan,Yoon, Won-Joon,Kim, Woo-Jin,Woo, Kyung-Mi,Baek, Jeong-Hwa,Lee, Gene,Ku, Young,van Wijnen, Andre J.,Ryoo, Hyun-Mo American Society for Biochemistry and Molecular Bi 2014 The Journal of biological chemistry Vol.289 No.29

<P>Mesenchymal cells alter and retain their phenotype during skeletal development through activation or suppression of signaling pathways. For example, we have shown that Wnt3a only stimulates osteoblast differentiation in cells with intrinsic osteogenic potential (<I>e.g.</I> MC3T3-E1 pre-osteoblasts) and not in fat cell precursors or fibroblasts (3T3-L1 pre-adipocytes or NIH3T3 fibroblasts, respectively). Wnt3a promotes osteogenesis in part by stimulating autocrine production of the osteoinductive ligand Bmp2. Here, we show that the promoter regions of the genes for <I>Bmp2</I> and the osteoblast marker <I>Alp</I> are epigenetically locked to prevent their expression in nonosteogenic cells. Both genes have conserved CpG islands that exhibit increased CpG methylation, as well as decreased acetylation and increased methylation of histone H3 lysine 9 (H3-K9) specifically in nonosteogenic cells. Treatment of pre-adipocytes or fibroblasts with the CpG-demethylating agent 5′-aza-2′-deoxycytidine or the histone deacetylase inhibitor trichostatin-A renders <I>Bmp2</I> and <I>Alp</I> responsive to Wnt3a. Hence, drug-induced epigenetic activation of <I>Bmp2</I> gene expression contributes to Wnt3a-mediated direct trans-differentiation of pre-adipocytes or fibroblasts into osteoblasts. We propose that direct conversion of nonosteogenic cells into osteoblastic cell types without inducing pluripotency may improve prospects for novel epigenetic therapies to treat skeletal afflictions.</P>

Biomimetic Approach to Stimulate Osteogenesis on Titanium Implant Surfaces Using Fibronectin Derived Oligopeptide

Cho, Young-Dan,Kim, Sung-Jun,Bae, Han-Sol,Yoon, Won-Joon,Kim, Kyung-Hwa,Ryoo, Hyun-Mo,Seol, Yang-Jo,Lee, Yong-Moo,Rhyu, In-Chul,Ku, Young Bentham Science 2016 CURRENT PHARMACEUTICAL DESIGN Vol.22 No.30

An Overview of Biomaterials in Periodontology and Implant Dentistry

Cho, Young-Dan,Seol, Yang-Jo,Lee, Yong-Moo,Rhyu, In-Chul,Ryoo, Hyun-Mo,Ku, Young Hindawi Publishing Corporation 2017 Advances In Materials Science And Engineering Vol.2017 No.1

<P>Material is a crucial factor for the restoration of the tooth or periodontal structure in dentistry. Various biomaterials have been developed and clinically applied for improved periodontal tissue regeneration and osseointegration, especially in periodontology and dental implantology. Furthermore, the biomimetic approach has been the subject of active research in recent years. In this review, the most widely studied biomaterials (bone graft material, barrier membrane, and growth or differentiation factors) and biomimetic approaches to obtain optimal tissue regeneration by making the environment almost similar to that of the extracellular matrix are discussed and specifically highlighted.</P>

Immediate Implant Placement at a Periapical Lesion Site: A Case Series

Cho, Young-Dan,Seol, Yang-Jo,Lee, Yong-Moo,Heo, Seong-Joo,Ku, Young American Academy of Implant Dentistry 2018 The Journal of oral implantology Vol.44 No.4

Histone acetylation together with DNA demethylation empowers higher plasticity in adipocytes to differentiate into osteoblasts

Cho, Young-Dan,Kim, Bong-Su,Kim, Woo-Jin,Kim, Hyun-Jung,Baek, Jeong-Hwa,Woo, Kyung-Mi,Seol, Yang-Jo,Ku, Young,Ryoo, Hyun-Mo Elsevier 2020 Gene Vol.733 No.-

<P><B>Abstract</B></P> <P>Bone regeneration has been a challenge for both researchers and clinicians. In the field of tissue engineering, much effort has been made to identify cell sources including stem cells. The present study aimed to induce trans-differentiation from adipocytes to osteoblasts using epigenetic modifiers; 5-aza-dC and/or trichostatin-A (TSA). 3 T3-L1 preadipocytes were treated with TSA (100 nM) and then with Wnt3a (50 ng/ml). Microscopic observation showed trans-differentiated cell morphology. Methylation-specific PCR and immunoblotting were performed to analyze the DNA methylation and histone acetylation patterns. The gene expression was determined by real-time PCR. Based on these <I>in vitro</I> experiments, <I>in vivo</I> mouse experiments supplemented the possibility of trans-differentiation by epigenetic modification. TSA induced the acetylation of lysine9 on histone H3, and a sequential Wnt3a treatment stimulated the expression of bone marker genes in adipocytes, suppressing adipogenesis and stimulating osteogenesis. Furthermore, TSA induced DNA hypomethylation, and a combined treatment with TSA and 5-aza-dC showed a synergistic effect in epigenetic modifications. The number of adipocytes and DNA methylation patterns of old (15 months) and young (6 weeks) mice were significantly different, and TSA and sequential Wnt3a treatments increased bone formation in the old mice. Collectively, our results confirmed cell trans-differentiation via epigenetic modifications and osteogenic signaling from adipocytes to osteoblasts for the bone regeneration <I>in vitro</I> and <I>in vivo</I>, and indicated that histone acetylation could induce DNA hypomethylation, enhancing the chance of trans-differentiation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Epigenetic modification permits the direct cell trans-differentiation. </LI> <LI> Histone acetylation together with DNA demethylation provides high plasticity in trans-differentiation. </LI> <LI> Trans-differentiation provides a promising alternative to iPSCs and a novel therapeutic avenue in the bone regeneration. </LI> </UL> </P>

Comparison of the Osteogenic Potential of Titanium and Modified Zirconia-Based Bioceramics

Cho, Young-Dan,Shin, Ji-Cheol,Kim, Hye-Lee,Gerelmaa, Myagmar,Yoon, Hyung-In,Ryoo, Hyun-Mo,Kim, Dae-Joon,Han, Jung-Suk Molecular Diversity Preservation International (MD 2014 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.15 No.3

<P>Zirconia is now favored over titanium for use in dental implant materials because of its superior aesthetic qualities. However, zirconia is susceptible to degradation at lower temperatures. In order to address this issue, we have developed modified zirconia implants that contain tantalum oxide or niobium oxide. Cells attached as efficiently to the zirconia implants as to titanium-based materials, irrespective of surface roughness. Cell proliferation on the polished surface was higher than that on the rough surfaces, but the converse was true for the osteogenic response. Cells on yttrium oxide (Y<SUB>2</SUB>O<SUB>3</SUB>)/tantalum oxide (Ta<SUB>2</SUB>O<SUB>5</SUB>)- and yttrium oxide (Y<SUB>2</SUB>O<SUB>3</SUB>)/niobium oxide (Nb<SUB>2</SUB>O<SUB>5</SUB>)-containing tetragonal zirconia polycrystals (TZP) discs ((Y, Ta)-TZP and (Y, Nb)-TZP, respectively) had a similar proliferative potential as those grown on anodized titanium. The osteogenic potential of MC3T3-E1 pre-osteoblast cells on (Y, Ta)-TZP and (Y, Nb)-TZP was similar to that of cells grown on rough-surface titanium. These data demonstrate that improved zirconia implants, which are resistant to temperature-induced degradation, retain the desirable clinical properties of structural stability and support of an osteogenic response.</P>

Effectiveness of dental implantation with the partial split-flap technique on vertical guided bone regeneration: a retrospective study

Cho, Young-Dan,Kim, Sungtae,Ku, Young Korean Academy of Periodontology 2021 Journal of Periodontal & Implant Science Vol.51 No.-

Purpose: This study aimed to evaluate the effectiveness of the partial split-flap technique with a K-incision on vertical guided bone regeneration (vGBR) and to retrospectively analyze the clinical and radiographic outcomes of dental implantation using this approach. Methods: In total, 78 patients who received 104 dental implants with vGBR, categorized as (1) pre-GBR and post-implantation and (2) simultaneous GBR and implantation, were enrolled. Data analysis was based on periapical radiographs, clinical photos, and dental records. The 2-sample t-test was used to compare the 2 surgical procedures. Results: The baseline vertical bone level, augmented bone height (ABH), and treatment duration were significantly higher in the pre-GBR procedure group. The survival rates of the implants were 96.1% and 94.8% in implant- and patient-based analyses, respectively. In Cox regression analysis, high rates of implant failure were found in the presence of ABH of ≥4 mm, smoking, and diabetes. Conclusions: Within the limitations of this retrospective study, the partial split-flap technique using a K-incision for vGBR showed stable clinical outcomes and favorable dental implant survival.