Expression Patterns and Function of Chromatin Protein HMGB2 during Mesenchymal Stem Cell Differentiation

Taniguchi, Noboru; Caramés, Beatriz; Hsu, Emily; Cherqui, Stéphanie; Kawakami, Yasuhiko; Lotz, Martin

doi:10.1074/jbc.m111.236984

Cited by 47 publications

(60 citation statements)

References 52 publications

(68 reference statements)

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“…Since HMGB2 underwent a more dramatic change in expression than HMGB1, we focused our attention on it. In agreement with our findings, Taniguchi et al report in human mesenchymal stem cells that HMGB2 expression was high in proliferating cells and decreased as the cells differentiated [38]. …”

Section: Discussionsupporting

confidence: 94%

Members of the high mobility group B protein family are dynamically expressed in embryonic neural stem cells

et al. 2013

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Neural Stem Cells (NSCs) are a distinct group of cells present in the embryonic and adult mammalian central nervous system (CNS) that are able to differentiate into neurons, astrocytes and oligodendrocytes. As NSC proliferation declines with age, factors that regulate this process need to be defined. To search for NSC regulatory factors, we performed a quantitative shotgun proteomics study that revealed that members of the High Mobility Group B (HMGB) family are highly expressed in NSCs. Using a neurosphere assay, we report the differential expression of HMGB 1, 2, 3, and 4 mRNAs in proliferating NSCs isolated from various time points during embryonic development, as well as the dynamic expression of HMGB1 and B2 mRNAs and proteins in differentiating embryonic NSCs. Expression of HMGB2 underwent the most dramatic changes during the developmental ages examined; as a result, we assessed its role in NSC proliferation and differentiation. We report the predominance of small diameter HMGB2-/- neurospheres in comparison to wild-type, which correlated with increased proliferation in these smaller HMGB2-/- neurospheres. Our data suggest that HMGB2 plays a regulatory role in NSC cell proliferation and maintenance pathways.

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Section: Discussionsupporting

confidence: 94%

Members of the high mobility group B protein family are dynamically expressed in embryonic neural stem cells

et al. 2013

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“…The structural defects in the SZ appear to be a consequence of cell depletion in this area. In previous studies, we identified the chromatin protein HMGB2 as a SZ specific protein and showed that it regulates SZ cell survival and differentiation (14–16). Analysis of gene expression patterns in cells from WT and Hmgb2 deficient mice showed that fibulin-3 levels are most significantly reduced in Hmgb2 deficient mice.…”

Section: Discussionmentioning

confidence: 99%

Role of Fibulin 3 in Aging‐Related Joint Changes and Osteoarthritis Pathogenesis in Human and Mouse Knee Cartilage

Hasegawa

Yonezawa

Taniguchi

et al. 2017

Arthritis & Rheumatology

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Objectives The EFEMP1 gene encoding fibulin-3 is specifically expressed in the superficial zone of articular cartilage. This study examined fibulin-3 expression patterns in joint aging and osteoarthritis (OA) and the role of fibulin-3 in OA pathogenesis. Methods Immunohistochemical analysis was performed on normal and OA human and mouse knee cartilage. Experimental OA was induced in wild type and fibulin-3−/− mice and OA severity was evaluated by histological scoring. To examine fibulin-3 function, chondrocyte monolayer cultures were transfected with siRNA for quantitative PCR and Western blot analyses. Bone marrow mesenchymal stem cells (MSC) were transduced with EFEMP1 lentivirus and analyzed for chondrogenesis markers. Results Fibulin-3 was specifically expressed in the SZ of normal cartilage in human and mouse knee joints and declined with aging. Both aging-related OA and experimental OA were significantly more severe in fibulin-3−/− mice compared with wild type mice. Fibulin-3 expression was high in undifferentiated MSC and decreased during chondrogenesis. Suppression of fibulin-3 by siRNA significantly increased SOX9, collagen II and aggrecan in articular chondrocytes, while overexpression of fibulin-3 inhibited chondrogenesis in MSC. Conclusion Fibulin-3 is specifically expressed in the SZ of articular cartilage and its expression is reduced in aging and OA. Fibulin-3 regulates differentiation of adult progenitor cells and its aging-related decline is an early event in OA pathogenesis. Preventing or restoring aging-associated loss of fibulin-3 in SZ chondrocytes has potential to delay or prevent onset of OA.

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“…The mechanism of transcriptional regulation of HMGB2 expression is unclear. HMGB2 −/− mice have increased susceptibility to apoptosis and have defects in spermatogenesis (Ronfani et al, 2001), chondrocyte development (Taniguchi et al, 2011; Taniguchi et al, 2009b), neurogenesis (Abraham et al, 2013b) and Wnt signaling (Taniguchi et al, 2009a). Thus, HMGB2 plays a critical role in the regulation of fertility, osteoarthritis, neuronal degeneration, and aging (Ly et al, 2000).…”

Section: Introduction and Historical Backgroundmentioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

798

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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Expression Patterns and Function of Chromatin Protein HMGB2 during Mesenchymal Stem Cell Differentiation

Cited by 47 publications

References 52 publications

Members of the high mobility group B protein family are dynamically expressed in embryonic neural stem cells

Members of the high mobility group B protein family are dynamically expressed in embryonic neural stem cells

Role of Fibulin 3 in Aging‐Related Joint Changes and Osteoarthritis Pathogenesis in Human and Mouse Knee Cartilage

HMGB1 in health and disease

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