Yi Liu

Ohio University, Athens, Ohio, United States

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Publications (68)319.44 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Many of the invading oral bacteria are known to produce considerable amounts of hydrogen sulfide (H2S). The toxic activity of exogenous H2S in periodontal tissue has been demonstrated, however, the role of endogenous H2S in the physiological function of periodontal tissue remains poorly understood. The purpose of the present study was to investigate the biological functions of hydrogen sulfide (H2S) on the proliferation and differentiation of human periodontal ligament stem cells (PDLSCs). PDLSCs were isolated from the periodontal ligament tissues of normal human volunteers or patients with periodontitis. Immunocytochemical staining, flow cytometry and western blot were used to examine the expression of H2S synthesizing enzymes CBS and CSE. The proliferation capacity of PDLSCs was determined by CCK-8 assay, CFSE analysis, and EdU assay. The osteogenic potential of PDLSCs was tested using ALP staining, alizarin red staining, and in vivo transplantation experiments. Oil red staining was used to analyze the adipogenic ability. We find that human PDLSCs express both CBS and CSE and produce H2S. Blocking the generation of endogenous H2S with CBS inhibitor hydroxylamine (HA) significantly attenuated PDLSCs proliferation and reduced the osteogenic and adipogenic differentiation capacity of PDLSCs. In contrast, CSE inhibitor DL-propargylglycine (PAG) had no effect on PDLSCs function. Exogenous H2S could inhibit the production of endogenous H2S and impair PDLSCs function in a dose-dependent manner. The physiological level of endogenousH2S maintains the proliferation and differentiation capacity of PDLSCs, and CBS may be the main source of endogenous H2S in PDLSCs.
    Journal of Periodontology 08/2015; DOI:10.1902/jop.2015.150240 · 2.71 Impact Factor
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    ABSTRACT: Regulatory T (Treg) cells are essential for maintenance of immune homeostasis. Here we found that hydrogen sulfide (H2S) was required for Foxp3(+) Treg cell differentiation and function and that H2S deficiency led to systemic autoimmune disease. H2S maintained expression of methylcytosine dioxygenases Tet1 and Tet2 by sulfhydrating nuclear transcription factor Y subunit beta (NFYB) to facilitate its binding to Tet1 and Tet2 promoters. Transforming growth factor-β (TGF-β)-activated Smad3 and interleukin-2 (IL-2)-activated Stat5 facilitated Tet1 and Tet2 binding to Foxp3. Tet1 and Tet2 catalyzed conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in Foxp3 to establish a Treg-cell-specific hypomethylation pattern and stable Foxp3 expression. Consequently, Tet1 and Tet2 deletion led to Foxp3 hypermethylation, impaired Treg cell differentiation and function, and autoimmune disease. Thus, H2S promotes Tet1 and Tet2 expression, which are recruited to Foxp3 by TGF-β and IL-2 signaling to maintain Foxp3 demethylation and Treg-cell-associated immune homeostasis. Copyright © 2015 Elsevier Inc. All rights reserved.
    Immunity 08/2015; 43(2). DOI:10.1016/j.immuni.2015.07.017 · 21.56 Impact Factor
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    ABSTRACT: microRNAs (miRNAs) act as regulatory signals for maintaining stemness, self-renewal, and differentiation of mesenchymal stem cells (MSCs), but whether miRNAs modulate the immunoregulatory function of MSCs remains largely unknown. Here, we show that miR-21 negatively regulates the activity of immunoregulatory cytokine TGF-β1 in MSCs. Consistently, bone marrow MSCs (BMMSCs) from miR-21(-/-) mice show enhanced immunosuppressive function by more TGF-β1 secretion and induce more CD4(+) Foxp3(+) regulatory T cells compared to wild-type BMMSCs in vitro, which anti-TGF-β1 antibody abrogates. Mechanistically, miR-21 inhibits TGF-β1 expression by targeting phosphatase and tensin homolog deleted on chromosome ten (PTEN) in BMMSCs. Downstream of PTEN, miR-21 promotes activation of Akt, and consequently increases activation of NF-κB pathway. Importantly, adoptive transfer of miR-21(-/-) BMMSCs into mice with experimental colitis more effectively ameliorate colonic inflammation in a TGF-β1-dependent manner. Thus, these findings indicate a previously uncovered mechanism of miR-21 control immunoregulatory function of BMMSCs through TGF-β1 inhibition. This article is protected by copyright. All rights reserved. © 2015 AlphaMed Press.
    Stem Cells 06/2015; DOI:10.1002/stem.2081 · 6.52 Impact Factor
  • 05/2015; 1:15002. DOI:10.1038/npjmgrav.2015.2
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    ABSTRACT: The interplay between osteoblasts and osteoclasts has a crucial role in maintaining bone homeostasis. In this study, we reveal that osteoblasts are capable of inducing osteoclast apoptosis by FAS ligand (FASL)/FAS signaling. Conditional knockout of FASL in osteoblasts results in elevated osteoclast numbers and activity, along with reduced bone mass, suggesting that osteoblastproduced FASL is required to maintain physiological bone mass. More interestingly, we show that osteoblasts from ovariectomized (OVX) osteoporotic mice exhibit decreased FASL expression that results from the IFN-γ- and TNF-α-activated NF-κB pathway, leading to reduced osteoclast apoptosis and increased bone resorption. Systemic administration of either IFN-γ or TNF-α ameliorates the osteoporotic phenotype in OVX mice and rescues FASL expression in osteoblasts. In addition, ovariectomy induces more significant bone loss in FASL conditional knockout mice than in control group with increased osteoclast activity in which the levels of RANKL and OPG remain unchanged. Taken together, this study suggests that osteoblast-induced osteoclast apoptosis via FASL/FAS signaling is a previously unrecognized mechanism that has an important role in the maintenance of bone mass in both physiological conditions and OVX osteoporosis.
    Cell Death and Differentiation 03/2015; · 8.18 Impact Factor
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    ABSTRACT: This study sought to investigate dimensional changes to the alveolar bone following extraction and application of novel devices used for obturation of socket orifice (socket cap) and space maintenance in sockets with facial dehiscence (socket cage). Six Macaca fascicularis had six teeth each removed according to the following intervention groups (groups A-C intact alveolar bone; D-E facial dehiscence): negative control (A); socket obturated with cap (B); filled with anorganic bovine bone mineral (ABBM) + socket cap (C); dehiscence negative control (D); socket cap + socket cage (E); ABBM + socket cap + socket cage (F). Serial CBCT scans at preoperatively, 6 and 12 weeks following intervention were compared to quantify linear alveolar bone alterations. Without therapeutic intervention, intact sockets exhibited significant reduction in width at the crestal 2 mm of the ridge crest within 6 weeks. Compared with the negative control sites which lost up to 52% of crestal bone width, sites treated with socket cap + ABBM lost at most 4% of bone width at the crestal 2 mm. Similar results were seen in the dehiscence groups, with the combination of socket cap + socket cage + ABBM maintaining the greatest socket width and height dimensions. Results from the current non-human primate study suggest that the socket cap and socket cage devices, when used in conjunction with xenograft proved effective in minimizing post-extraction socket width loss and height seen in both intact sockets and sockets with facial dehiscence defects. © 2015 The Authors. Clinical Oral Implants Research Published by John Wiley & Sons Ltd.
    Clinical Oral Implants Research 02/2015; DOI:10.1111/clr.12521 · 3.89 Impact Factor
  • Gang Ding · Jianyi Niu · Yi Liu
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    ABSTRACT: Dental pulp stem cells (DPSCs) possess self-renewal capability, multi-lineage differentiation potential, and can generate a dentin-pulp-like tissue in vivo, which is promising for tooth regeneration. To enlarge the cells resource of DPSCs and explore the feasibility of DPSCs-mediated immune therapy, it is prerequisite to investigate the immunological properties of DPSCs and the underlying mechanisms. Human DPSCs and peripheral blood mononuclear cells were isolated and cultured. Then we used lymphocytes proliferation assays, cytokines detection, Transwell cultures, neutralization experiments, and flow cytometry to examine the in vitro immune characteristics of DPSCs. We found that DPSCs failed to stimulate allogeneic T cells proliferation and suppressed T cells proliferation, B cells proliferation, and mixed lymphocyte reaction. In addition, DPSCs could up-regulate IL-10, down-regulate the production of IL-2, IL-17, and IFN-γ, and did not affect the production of IL-6. Monoclonal antibody against transforming growth factor-β1 restored the T cells proliferation inhibited by DPSCs. Moreover, the population of regulatory T cells increased significantly and T-helper 17 cells decreased significantly in peripheral blood mononuclear cells co-cultured with DPSCs. These data confirmed that DPSCs are low immunogenic, could inhibit the proliferation of lymphocytes, regulate the production of cytokines in vitro, and the secretion of transforming growth factor-β1 may be involved in this event.
    Human Cell 01/2015; 28(2). DOI:10.1007/s13577-014-0106-y · 1.41 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):3364-3364. DOI:10.1158/1538-7445.AM2014-3364 · 9.33 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):5257-5257. DOI:10.1158/1538-7445.AM2014-5257 · 9.33 Impact Factor
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    ABSTRACT: ATP plays central roles in cancer metabolism and the Warburg effect. Intratumoral ATP concentrations are up to 104 times higher than those of interstitial ATP in normal tissues. However, extracellular ATP is not known to enter cancer cells. Here we report that human A549 lung cancer cells internalized extracellular ATP by macropinocytosis as demonstrated by colocalization of a nonhydrolyzable fluorescent ATP and a macropinocytosis tracer high-molecular-weight dextran, as well as by a macropinocytosis inhibitor study. Extracellular ATP also induced increase of intracellular ATP levels, without involving transcription and translation at significant levels, and cancer cells’ resistance to ATP-competitor anticancer drugs, likely through the mechanism of ATP internalization. These findings, described for the first time, have profound implications in ATP-sharing among cancer cells in tumors and highlight a novel anticancer target.
  • Yi Liu · Ruili Yang · Songtao Shi
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    ABSTRACT: Mesenchymal stem cell-based regenerative medicine is a promising approach for functional tissue reconstruction. A recent study showed that host immune cells regulated bone marrow mesenchymal stem cell (BMMSC)-mediated tissue regeneration. However, it is unknown whether systemic infusion of BMMSCs, which induces immune tolerance, affects cell-based tissue regeneration. In this study, we showed that BMMSCs possessed an immunomodulatory function in vitro. Moreover, systemic infusion of BMMSCs reduced IFN- and TNF- levels in the implantation sites via upregulation of regulatory T cells (Tregs), resulting in marked enhancement of cell-based bone regeneration, but with only limited contribution by BMMSC homing. Furthermore, we showed that systemic BMMSC infusion significantly improved cell-based repair of critical-sized calvarial defects in a murine model. These results suggested a new approach to enhance cell-based bone regeneration.
    Tissue Engineering Part A 08/2014; 21(3-4). DOI:10.1089/ten.TEA.2013.0673 · 4.70 Impact Factor
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    ABSTRACT: ATP plays central roles in cancer metabolism and the Warburg effect. Intratumoral ATP concentrations are up to 10(4) times higher than those of interstitial ATP in normal tissues. However, extracellular ATP is not known to enter cancer cells. Here we report that human A549 lung cancer cells internalized extracellular ATP by macropinocytosis as demonstrated by colocalization of a nonhydrolyzable fluorescent ATP and a macropinocytosis tracer high-molecular-weight dextran. Extracellular ATP also induced increase of intracellular ATP levels and cancer cells' resistance to ATP-competitor anticancer drugs, likely through the mechanism of ATP internalization. These findings, described for the first time, have profound implications in ATP-sharing among cancer cells in tumors and highlight a novel anticancer target.
    Cancer Letters 06/2014; 351(2). DOI:10.1016/j.canlet.2014.06.008 · 5.62 Impact Factor
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    ABSTRACT: Bone marrow mesenchymal stem cells (BMMSCs) have been used to treat a variety of autoimmune diseases in clinics. However, the therapeutic effects are largely dependent on the immunomodulatory capacity of culture-expanded BMMSCs. In the present study, we show that aspirin (ASA)-treated BMMSCs have significantly improved immunomodulatory function, as indicated by upregulation of regulatory T cells (Tregs) and downregulation of Th17 cells via the 15d-PGJ2/PPARγ/TGF-β1 pathway. Furthermore, the therapeutic effect of ASA-pretreated BMMSCs was confirmed in a dextran sodium sulfate (DSS)-induced experimental colitis mouse model, in which systemic infusion of ASA-pretreated BMMSCs significantly ameliorated disease activity index (DAI) and colonic inflammation, along with an increased number of Tregs and decreased number of Th17 cells. Taken together, our results suggest that aspirin treatment is a feasible strategy to promote BMMSC-based immunomodulation.
    Stem cells and development 04/2014; 23(17). DOI:10.1089/scd.2014.0081 · 3.73 Impact Factor
  • Yingying Su · Songtao Shi · Yi Liu
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    ABSTRACT: Mesenchymal stem cell (MSC)-based regenerative medicine represents a promising frontier for bone reconstruction. Significant efforts have been devoted to clarifying the capacities of MSCs to repair or reconstruct bone tissue. This review provides a concise summary of current knowledge pertaining to the possible mechanisms of MSC action in the regeneration of bone, with particular focus on the interplay between donor MSCs and host immune response in the process of new bone regeneration. This article is protected by copyright. All rights reserved.
    Oral Diseases 04/2014; 20(7). DOI:10.1111/odi.12248 · 2.43 Impact Factor
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    ABSTRACT: Gaseous signaling molecules such as hydrogen sulfide (H2S) are produced endogenously and mediate effects through diverse mechanisms. H2S is one such gasotransmitters that regulates multiple signaling pathways in mammalian cells, and abnormal H2S metabolism has been linked to defects in bone homeostasis. Here, we demonstrate that bone marrow mesenchymal stem cells (BMMSCs) produce H2S in order to regulate their self-renewal and osteogenic differentiation, and H2S deficiency results in defects in BMMSC differentiation. H2S deficiency causes aberrant intracellular Ca(2+) influx because of reduced sulfhydration of cysteine residues on multiple Ca(2+) TRP channels. This decreased Ca(2+) flux downregulates PKC/Erk-mediated Wnt/β-catenin signaling which controls osteogenic differentiation of BMMSCs. Consistently, H2S-deficient mice display an osteoporotic phenotype that can be rescued by small molecules that release H2S. These results demonstrate that H2S regulates BMMSCs and that restoring H2S levels via nontoxic donors may provide treatments for diseases such as osteoporosis that can arise from H2S deficiencies.
    Cell stem cell 04/2014; 15(1). DOI:10.1016/j.stem.2014.03.005 · 22.27 Impact Factor
  • Yi Liu · Jingchao Hu · Songlin Wang
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    ABSTRACT: In the oral maxillofacial region, there are significant demands for repairing severe tissue defects caused by congenital malformations, oncologic resection, post-traumatic loss, and pathologic degenerative destruction such as periodontitis. Mesenchymal stem cells (MSCs) are adult stem cells whose multipotency has been investigated for therapeutic applications. This review highlights the main MSCs involved in the tissue regeneration of oral maxillofacial region and recent advances in dental MSC-based tissue regeneration and treatments in this region. MSCs isolated from oral maxillofacial sources have higher proliferation rates and are more capable of forming bone and dental tissues. Large animal models of oral diseases or defects were established and treated with MSCs. Miniature pigs or dogs more closely mimic disease in humans and provide a useful means for translating research into clinical applications. MSCs exert other beneficial effects, including immunomodulation and paracrine processes. The immunoregulatory properties of MSCs facilitate their application to oral diseases and tissue regeneration. Besides autologous MSCs being an excellent cell source for tissue engineering and regenerative medicine, allogeneic MSC-based treatment also provides a safe and effective therapeutic modality, the use of allogeneic MSCs in highly standardized clinical trials could lead to a better understanding of their real-life applications, which sheds light on potential clinical applications for treating oral diseases.
    Histology and histopathology 03/2014; 29(8). · 2.10 Impact Factor
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    ABSTRACT: A series of novel 9-O-acetyl-4'-substituted 16-membered macrolides derived from josamycin has been designed and synthesized by cleavage of the mycarose of josamycin and subsequent modification of the 4'-hydroxyl group. These derivatives were evaluated for their in vitro antibacterial activities against a panel of Staphylococcus aureus and Staphylococcus epidermidis. 15 (4'-O-(3-Phenylpropanoyl)-9-O-acetyl-desmycarosyl josamycin) and 16 (4'-O-butanoyl-9-O-acetyl-desmycarosyl josamycin) exhibited comparable activities to josamycin against S. aureus (MSSA) and S. epidermidis (MSSE).
    Bioorganic & medicinal chemistry letters 12/2013; 24(2). DOI:10.1016/j.bmcl.2013.12.029 · 2.42 Impact Factor
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    ABSTRACT: Abnormal stem cell function makes a known contribution to many malignant tumors, but the role of stem cells in benign tumors is not well understood. Here, we show that ossifying fibroma (OF) contains a stem cell population that resembles mesenchymal stem cells (OFMSCs) and is capable of generating OF-like tumor xenografts. Mechanistically, OFMSCs show enhanced TGF-β signaling that induces aberrant proliferation and deficient osteogenesis via Notch and BMP signaling pathways, respectively. The elevated TGF-β activity is tightly regulated by JHDM1D-mediated epigenetic regulation of thrombospondin-1 (TSP1), forming a JHDM1D/TSP1/TGF-β/SMAD3 autocrine loop. Inhibition of TGF-β signaling in OFMSCs can rescue their abnormal osteogenic differentiation and elevated proliferation rate. Furthermore, chronic activation of TGF-β can convert normal MSCs into OF-like MSCs via establishment of this JHDM1D/TSP1/TGF-β/SMAD3 autocrine loop. These results reveal that epigenetic regulation of TGF-β signaling in MSCs governs the benign tumor phenotype in OF and highlight TGF-β signaling as a candidate therapeutic target.
    Cell stem cell 11/2013; 13(5):577-89. DOI:10.1016/j.stem.2013.08.010 · 22.27 Impact Factor
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    ABSTRACT: A series of new 4″-O-desosaminyl clarithromycin derivatives were designed and synthesized. The efficient synthesis routes of 6-deoxy-desosamine donors 8 and 11 were developed and the methodology of glycosylation of clarithromycin 4″-OH with desosamine was studied. The activities of the target compounds were tested against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed activities against macrolide sensitive pathogens, and compounds 19 and 22 displayed significant improvement of activities against sensitive pathogens and two strains of MRSE, which verified the importance of desosamine in the interaction of macrolide and its receptor, and offered valuable information of the SAR of macrolide 4″-OH derivatives.
    Bioorganic & medicinal chemistry letters 10/2013; 23(23). DOI:10.1016/j.bmcl.2013.09.083 · 2.42 Impact Factor

Publication Stats

2k Citations
319.44 Total Impact Points


  • 2011–2014
    • Ohio University
      • Department of Biological Sciences
      Athens, Ohio, United States
  • 2010–2014
    • Molecular and Cellular Biology Program
      Seattle, Washington, United States
    • Capital Medical University
      • School of Stomatology
      Peping, Beijing, China
    • Government of the People's Republic of China
      Peping, Beijing, China
  • 2013
    • Peking Union Medical College Hospital
      Peping, Beijing, China
  • 2009–2013
    • University of Southern California
      • Center for Craniofacial Molecular Biology
      Los Angeles, California, United States
  • 2012
    • Chinese Academy of Medical Sciences
      Peping, Beijing, China
  • 2004–2012
    • Università degli Studi di Genova
      • Dipartimento di Medicina sperimentale (DIMES)
      Genova, Liguria, Italy