Abstract：
:Insulin mimetics, including zinc containing compounds, have previously been shown to influence chondrogenesis as it relates to healing of fractures in various preclinical models. However, the mechanism by which these compounds drive chondrogenic differentiation is yet undefined. Here, via next-generation sequencing (NGS) and in vitro functional validation, we show that Zinc Chloride (ZnCl2) induces expression of both chondrogenic genes (Sox9, Runx1, collagen) as well as genes associated with VEGF-mediated signal transduction, including VEGF receptors 1 and 2 and their ligands; VEGF-A and VEGF-B. Noticeably, although insulin was able to also induce expression of these pro-angiogenic and pro-chondrogenic genes, the impact of insulin on expression of VEGF receptor and ligand genes was marginal when compared to that of ZnCl2. Furthermore, while the VEGFR antagonist, Axitinib, was able to attenuate the pro-chondrogenic effects of both insulin and ZnCl2; a reduction in gene and protein expression was most profoundly observed when the antagonist was applied to cells treated with ZnCl2. Taken together, these data suggest an important role for the VEGF-mediated signal transduction pathways in the positive effects observed when applying zinc-based compounds as adjuvants for chondrogenesis-mediated fracture healing. In this regard, further mechanistic evaluation of ZnCl2 and other zinc-containing insulin mimetics may support rational design of therapies targeted for disease indications associated with impaired fracture healing.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Hozain S,Hernandez A,Fuller J,Sharp G,Cottrell Jdoi
10.1016/j.yexcr.2020.112436subject
Has Abstractpub_date
2021-01-21 00:00:00pages
112436issue
2eissn
0014-4827issn
1090-2422pii
S0014-4827(20)30689-3journal_volume
399pub_type
杂志文章abstract：:Breast tumor cells enter the bloodstream long before the development of clinically evident metastasis. However, the early presence of such bloodborne cells predicts poor patient outcome. Nearly 90% of human breast tumors arise as carcinomas from mammary epithelial cells, so it is important to study how these cells res...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2007.02.001
更新日期：2007-04-15 00:00:00
abstract：:Distal-less homeobox 5 (Dlx5) is a pro-osteogenic but anti-adipogenic transcription factor that regulates lineage commitment in mesenchymal stem cells. Although the expression of Dlx5 is known to be decreased by adipogenic stimuli, the mechanism of Dlx5 down-regulation has not yet been clarified. MicroRNAs (miRNAs) ar...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2013.04.020
更新日期：2013-08-15 00:00:00
abstract：:Terminally differentiated skeletal muscle myotubes are arrested in G0 phase of the cell cycle and are unable to be released from this arrest by stimulation with mitogens including serum and growth factors. To inspect a possibility of reversing the quiescence at the G0 phase, we have exploited the mouse skeletal muscle...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1994.1258
更新日期：1994-09-01 00:00:00
abstract：:In preceding studies, the IP3-sensitive Ca2+ store of the hamster insulinoma cell line, HIT, was detected in cell surface protrusions such as microvilli and related membrane structures [Lange, K., and Brandt, U. (1993) FEBS Lett. 320, 183-188; and (1993) FEBS Lett. 325, 205-209]. In this study, these experiments were ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1996.0316
更新日期：1996-11-01 00:00:00
abstract：:The micronucleus of Paramecium tetraurelia normally gives rise to the macronucleus by going through the series of nuclear events of meiosis, mitosis and fusion during sexual reproduction. By transplanting the micronucleus from vegetative cells into early exconjugants, we have persuaded the micronucleus to take a short...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(83)90437-8
更新日期：1983-03-01 00:00:00
abstract：:The importance of mononuclear leukocyte (MO) adhesion to dysfunctional endothelium and migration to the subendothelial space in the early phases of atherogenesis is well established. Few studies have addressed the relevance of polymorphonuclear leukocytes (PMNs) in the context of evolving lesions, and nothing is known...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.2001.5459
更新日期：2002-04-01 00:00:00
abstract：:Wnt1 and -5a have been shown to modulate the proliferation and differentiation of midbrain dopaminergic (DA) neurons. However, it is not known whether other Wnts or which Frizzled (Fz) receptors are expressed in the developing midbrain. We found that 13 out of 19 Wnts, all 10 Fzs, and several intracellular Wnt signali...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2006.01.032
更新日期：2006-05-15 00:00:00
abstract：:Bullous pemphigoid antigen 1 (BPAG1) is a member of the plakin family of proteins that is involved in cross-linking the cytoskeletal elements and attaching them to cell junctions. BPAG1 null mice develop severe degeneration of sensory neurons that was attributed in part due to the absence of a splice variant called BP...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2006.04.025
更新日期：2006-09-10 00:00:00
abstract：:The existence of two different pathways for cell death has been postulated. In addition to the passive and traumatic process leading to necrosis, an active program characterized by organelle integrity and called apoptosis has been described. A positive correlation between the apoptotic cell death process and oxidative...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1995.1311
更新日期：1995-09-01 00:00:00
abstract：:The KIAA0101/p15(PAF)/OEATC-1 protein was initially isolated in a yeast two-hybrid screen for proliferating cell nuclear antigen (PCNA) binding partners, and was shown to bind PCNA competitively with the cell cycle regulator p21(WAF). PCNA is involved in DNA replication and damage repair. Using polyclonal antisera rai...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2005.09.020
更新日期：2006-01-01 00:00:00
abstract：:Despite over 30 years of work, the fundamental structure of eukaryotic chromatin remains controversial. Here, we review the roots of this controversy in disparities between results derived from studies of chromatin in nuclei, chromatin isolated from nuclei, and chromatin reconstituted from defined components. Thanks t...
journal_title：Experimental cell research
pub_type： 杂志文章,评审
doi：10.1016/j.yexcr.2012.02.014
更新日期：2012-07-15 00:00:00
abstract：:Nucleoside diphosphate (NDP) kinases, responsible for the synthesis of nucleoside triphosphates and produced by the nm23 genes, are involved in numerous regulatory processes associated with proliferation, development, and differentiation. Their possible role in providing the GTP/ATP required for sperm function is unkn...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/s0014-4827(03)00268-4
更新日期：2003-10-01 00:00:00
abstract：:In S. cerevisiae the induction of heat-shock protein (HSP) synthesis is accompanied by a decrease in the cytoplasmic and vacuolar pH as determined by means of [31P]NMR spectroscopy. The relationship of HSP synthesis and acidification of the cytoplasmic pH is dose-dependent under a variety of treatments (temperature in...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(87)90117-0
更新日期：1987-05-01 00:00:00
abstract：:Individual tumor cells utilize one of two modes of motility to invade the extracellular matrix, mesenchymal or amoeboid. We have determined that the diterpenoid genkwanine M (GENK) enhances the mesenchymal mode of cell motility that is intrinsic to HT-1080 osteosarcoma cells, stimulates a mesenchymal mode of motility ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2013.01.005
更新日期：2013-04-01 00:00:00
abstract：:Signalling from the extracellular matrix (ECM) is a fundamental cellular input that sustains proliferation, opposes cell death and regulates differentiation. Through integrins, cells perceive both the chemical composition and physical properties of the ECM. In particular, cell behaviour is profoundly influenced by the...
journal_title：Experimental cell research
pub_type： 杂志文章,评审
doi：10.1016/j.yexcr.2015.10.034
更新日期：2016-04-10 00:00:00
abstract：:Cultured megakaryocytes, isolated from guinea pig bone marrow, were treated with buffer or adenosine diphosphate (ADP) (10 microM) on plain or coated glass surfaces. Control cells were rounded and non-adherent. The nucleotide induced the cells to spread to several times the initial diameter, and to become flattened an...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(84)90649-9
更新日期：1984-06-01 00:00:00
abstract：:In a previous paper (Barboro et al., 1993, Biophys. J. 65, 1690-1699) we have shown that cancer development in the resistant hepatocyte model of Solt and Farber is characterized by the progressive unfolding of the higher-order structure of chromatin. A possible functional role of decondensation phenomena in cell trans...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1996.0182
更新日期：1996-06-15 00:00:00
abstract：:Ran, a nuclear GTPase, and a number of interacting proteins, including regulators RanGEF1 and RanGAP1, are involved in nucleocytoplasmic transport. We have identified a new temperature-sensitive mutation in budding yeast YRB1 gene, which encodes Ran-binding protein-1 (RanBP1). In contrast to other yrb1 alleles, the ne...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1998.4174
更新日期：1998-10-10 00:00:00
abstract：:The activation of Cdc2 kinase induces the entry into M-phase of all eukaryotic cells. We have developed a cell-free system prepared from prophase-arrested Xenopus oocytes to analyze the mechanism initiating the all-or-none activation of Cdc2 kinase. Inhibition of phosphatase 2A, the major okadaic acid-sensitive Ser/Th...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1998.4220
更新日期：1998-11-01 00:00:00
abstract：:Increased protein aggregation and altered cell signaling accompany many neurodegenerative diseases including Huntington's disease (HD). Cell stress is counterbalanced by signals mediating cell repair but the identity of these are not fully understood. We show here that the mammalian target of rapamycin (mTOR) pathway ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2011.08.020
更新日期：2012-01-01 00:00:00
abstract：:ADvF11 (F11), a Chinese Hamster Ovary (CHO) cell variant, is defective in its ability to adhere to fibronectin (Fn)-coated substrata but will adhere to substrata coated with poly-L-lysine, conA or extracellular matrix (ECM) [1]. We have observed that both F11 and CHO wild-type (WT) cells were able to bind 3H-Fn beads ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(84)90236-2
更新日期：1984-05-01 00:00:00
abstract：:Oxysterol-binding protein (OSBP)-related proteins (ORPs) are conserved lipid binding proteins found in organisms ranging from yeast to mammals. Recent findings have indicated that these proteins mainly localize to contact sites of 2 different membranous organelles. ORP6, a member of the ORP subfamily III, is one of th...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2018.07.025
更新日期：2018-09-15 00:00:00
abstract：:Hypoxia can activate the endothelium toward a pro-inflammatory phenotype and enhance leukocyte adhesion. This process is involved in pathological conditions such as vascular remodeling or ischemia-reperfusion injury. This study was aimed to obtain a global picture of the response of the endothelial cells to hypoxia wi...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2008.11.020
更新日期：2009-03-10 00:00:00
abstract：OBJECTIVES:Our purpose was to investigate the role of the nitric oxide (NO) signaling pathway in the regulation of ciliary beat frequency (CBF) in mouse nasal and tracheal epithelial cells. METHODS:We studied the effects of the NO donor l-arginine (L-Arg) and specific inhibitors of the NO signaling pathway on CBF of b...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2011.07.007
更新日期：2011-10-15 00:00:00
abstract：:HALF1 (human activator of liver function 1) is a closed DNA duplex implicated in reversion of rat dedifferentiated C2 hepatoma cells to a well-differentiated state. A copy of HALF1 is found in high-molecular-weight DNA in the human genome. The genomic equivalent of HALF1 and its flanking sequences [gH(5'-3') fragment]...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1994.1180
更新日期：1994-07-01 00:00:00
abstract：:Transforming growth factor-beta (TGF-beta) signaling mainly relies on the TGF-beta receptor-Smad pathway. Meanwhile, TGF-beta binding to its receptors initiates the degradation of several key components of its signaling pathway. The degradation of these components, including both positive and negative transducers, is ...
journal_title：Experimental cell research
pub_type： 杂志文章,评审
doi：10.1016/j.yexcr.2003.07.007
更新日期：2003-12-10 00:00:00
abstract：:We have studied the morphological alterations of the lysosomal compartment in rat hepatocytes following intraperitoneal administration of leupeptin, using electron microscopy and cytochemical techniques. At 30 min after the injection, autophagic vacuoles (autophagosomes and autolysosomes), containing cytoplasmic organ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(83)90436-6
更新日期：1983-03-01 00:00:00
abstract：:Previous studies have indicated that space flight affects the activation of lymphocytes from humans, monkeys, and rodents. In rats, where lymphocytes from blood, spleen, and lymph nodes have been tested, the accumulated data suggest that the effects of flight on various cells are lymphoid organ-specific. Thus, cells m...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1995.1210
更新日期：1995-07-01 00:00:00
abstract：:The extraocular muscles (EOM) are spared from pathology in aging and many forms of muscular dystrophy. Despite many studies, this sparing remains an enigma. The EOM have a distinct embryonic lineage compared to somite-derived muscles, and we have shown that they continuously remodel throughout life, maintaining a popu...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2011.01.018
更新日期：2011-04-01 00:00:00
abstract：:Screening for microbial metabolites that induce transcriptional activation of the SV40 promoter resulted in the identification of two known compounds, FR901228 and trichostatin A (TSA). FR901228 is a potent antitumor drug that is currently under clinical investigation. TSA is a specific inhibitor of histone deacetylas...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1998.4027
更新日期：1998-05-25 00:00:00
