Inflammation and Regeneration
Online ISSN : 1880-8190
Print ISSN : 1880-9693
34 巻, 2 号
選択された号の論文の7件中1~7を表示しています
Special Issue: Genomic Era
Brief Review
Mini Review
  • Chikash Terao
    2014 年 34 巻 2 号 p. 071-077
    発行日: 2014年
    公開日: 2014/04/25
    ジャーナル フリー
    Rheumatoid arthritis (RA) is the most common chronic arthritis in the world. RA is characterized by inflammatory joint synovitis and a resultant joint destruction. Patients with RA often display positivity for rheumatoid factor (RF) and/or anti-citrullinated peptide antibody (ACPA). Methotrexate is an anchor oral drug to treat RA. Biological agents, targeting TNF or IL-6R, are efficient treatment to RA which prevent joint destruction in patients with RA. However, patients with RA are heterogeneous. Joint destruction develops rapidly in some patients but slowly in others. ACPA and/or RF are not positive for all patients with RA. Moreover, positivities of ACPA and RF do not always correlate with each other. About 30% of patients with RA do not respond to biological treatment. What kind of factors determines the heterogeneity of RA? Genetic and environmental effects are assumed to explain these variance. In this review, we focus on genetic components and review how much variance of susceptibility to RA or RA phenotype can be explained and determined by genetic components. Recent technological advancement has enabled us to perform genome-wide association studies to detect susceptibility loci to complex diseases with an unbiased approach. More than 100 susceptibility loci to RA have been detected so far, and functional analyses have been successfully performed for some. Autoantibody status in patients with RA is strongly associated with HLA alleles. Unfortunately, detecting markers associated with response to treatment in patients with RA have not been very successful to date.
  • Minoru Nakamura
    2014 年 34 巻 2 号 p. 078-086
    発行日: 2014年
    公開日: 2014/04/25
    ジャーナル フリー
    High concordance rate in monozygotic twins and familial clustering of patients with primary biliary cirrhosis (PBC) indicate the involvement of strong genetic factors in the development of PBC. To identify susceptibility loci for PBC in Japanese population, a genome-wide association study (GWAS) and subsequent replication study were performed in a total of 1327 PBC cases and 1120 healthy controls. Two significant (p<5x10-8) non-HLA susceptibility loci (TNFSF15 and POU2AF1) for PBC were identified. In addition, 10 loci (CD80, IKZF3, IL7R, NFKB1, STAT4, CXCR5, TNFAIP2, MAP3K7IP1, rs6974491, DENND1B) out of 21 non-HLA susceptibility loci for PBC which were recently identified in European descent showed significant associations in Japanese population. These results indicated the importance of two disease-pathways in both European descent and Japanese population, Th1/Th17 differentiation of T cells (CD80, IL12A, IL12RB2, STAT4, TNFSF15) and B cell differentiation to plasma cells (IL7R, CXCR5, POU2AF1, SPIB, IKZF3), although there are some ethnic differences in disease-susceptibility loci for PBC. In addition, the study for systemic and local expression of TNF-like ligand 1A (TL1A), which is encoded by TNFSF15, indicated that TL1A may be involved in the pathogenesis of PBC.
  • Akira Watanabe, Naoki Amano, Yumieu Tokunaga, Unyanee Poolsap, Shinya ...
    2014 年 34 巻 2 号 p. 087-093
    発行日: 2014年
    公開日: 2014/04/25
    ジャーナル フリー
    The discovery of induced pluripotent stem (iPS) cells have opened the doors for further disease research, drug screening, as well as regenerative medicine. To achieve clinical application of iPS cells, it is important to select proper iPS cell lines that do not harbor the risk of tumorigenicity. Thus, it is desired to establish methodologies for evaluating the safety of iPS cells, particularly in terms of genome integrity. Massively parallel sequencing can be used to monitor genomic aberrations such as the subchromosomal and the single nucleotide variations. Refined mutation analyses of iPS and founder cells revealed that some of the iPS cell-specific variations were also detected in rare populations of the founder cells by consequence of capturing the heterogeneity of the founder cells. In this review, we highlight recent analyses used to evaluate the genome integrity of iPS cells, discuss future of directions for precise assessment of the safety of iPS cells, and address issues that should be overcome.
  • Takashi Minami
    2014 年 34 巻 2 号 p. 094-102
    発行日: 2014年
    公開日: 2014/04/25
    ジャーナル フリー
    Activation and dysfunction of the endothelium underlie many vascular disorders including atherosclerosis, tumor growth, and inflammation. Endothelial cell activation is mediated by many different extracellular signals, which results in overlapping, yet, distinct patterns of gene expression. Comparative ChIP-seqs with either STAT6, GATA2, or NFATc1 antibody between endothelial cells and erythroids or lymphoids revealed that each transcription factor bound the consensus recognition motif genome-widely, but the bound regions showed exclusive cell type specificity and strong correlation to the each cell's crucial function. By using the ChIP-seqs with epigenetic histone modification in endothelium, constitutively expressed GATA2 and chronic IL-4-stimulated STAT6 binding regions were detected at both proximal and distal promoters. In contrast, VEGF-stimulated NFATc1 preferentially bound to the proximal promoters, the majority of which were pre-opened chromatin due to responding to the acute VEGF activation signal. This review is to combine our recent genome/ epigenome wide ChIP-seqs information and the related literatures as well as to summarize the crucial roles of tight regulation by the endothelial cell activation that is pathologically leading to tumor growth and inflammation.
Mini Review
  • Koshiro Sonomoto, Kunihiro Yamaoka, Yoshiya Tanaka
    2014 年 34 巻 2 号 p. 103-108
    発行日: 2014年
    公開日: 2014/04/25
    ジャーナル フリー
    Wingless-type MMTV integration site (Wnt) family molecules, a family of secreted glycoproteins have now gathered attention as a therapeutic target. Drug innovation targeting the canonical Wnt pathway is in the most interest since its molecular mechanism is well understood and clinical trials are in progress for osteoporosis. Recent findings have revealed the contribution of the non-canonical Wnt pathway in malignant tumors suggesting this pathway as a new treatment target, but it is relatively less understood. Recently, several reports have demonstrated the involvement of the non-canonical Wnt pathway in the bone metabolism. Therefore, we have compiled the current understanding of the non-canonical Wnt pathway in association with bone metabolism.
Original Article
  • Masao Ozasa, Keigo Sawada, Tomoaki Iwayama, Satomi Yamamoto, Chiaki Mo ...
    2014 年 34 巻 2 号 p. 109-116
    発行日: 2014年
    公開日: 2014/04/25
    ジャーナル フリー
    Several stem and progenitor cells are currently under investigation for their application in cell-based therapy for periodontal tissue regeneration. The present study evaluates periodontal tissue regeneration following transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) into periodontal tissue defects in beagle dogs.
    ADMPCs were isolated from the greater omentum and their characteristics were identified using in vitro studies. Flow cytometric analysis demonstrated that the isolated ADMPCs were CD29+, CD44+, and CD90+. When cultured in mineralization-inducing media, these cells upregulated osteogenic genes and formed calcified nodules. Gene expression of the periodontal ligament specific gene, PLAP-1, was also increased. In addition, culture in adipogenic media resulted in accumulation of intracellular lipid droplets, suggesting multi-lineage differentiation capability of ADMPCs.
    The efficacy of ADMPC transplantation for periodontal regeneration was evaluated using a beagle dog model. The furcation bone defects were surgically created and autologous transplantation of ADMPCs with fibrin gel was performed. Six weeks after transplantation, periodontal regeneration was analyzed using micro-CT, which showed a significant increase in bone formation at sites where ADMPCs were applied compared with control sites. Histological analysis revealed new cementum formation on the instrumented root surface was significantly increased following ADMPC transplantation and connective tissue fibers were inserted vertically in newly formed bone and cementum. Importantly, no instances of undesirable healing, such as root resorption or ankylosis, were observed at any sites examined. These results indicate that transplantation of ADMPCs with fibrin gel promotes periodontal tissue regeneration.
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