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Article: Improved method for isolating high-quality RNA from mouse bone with RNA

Pedersen, Kim B / Williams, Ashlee / Watt, James / Ronis, Martin J

2019 Volume 11, Page(s) 100211

Abstract: Accurate gene expression analysis of bone requires the ability to isolate RNA of good quality. Isolation of intact RNA from frozen bone tissue is problematic since RNA rapidly becomes degraded after thawing. Since we are interested in assessing gene ... ...

Abstract	Accurate gene expression analysis of bone requires the ability to isolate RNA of good quality. Isolation of intact RNA from frozen bone tissue is problematic since RNA rapidly becomes degraded after thawing. Since we are interested in assessing gene expression from both bone marrow and mineralized bone, we aimed to develop improved simple, robust and statistically validated methods providing high-quality RNA from both mouse femur shaft and femur marrow. RNA integrity was quantified by the RNA Integrity Number (RIN) measured on a TapeStation. While the RNA stabilization reagent RNA
Language	English
Publishing date	2019-05-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	2821774-3
ISSN	2352-1872
ISSN	2352-1872
DOI	10.1016/j.bonr.2019.100211
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Article ; Online: Adverse Effects of Nutraceuticals and Dietary Supplements.

Ronis, Martin J J / Pedersen, Kim B / Watt, James

Annual review of pharmacology and toxicology

2017 Volume 58, Page(s) 583–601

Abstract: Over 70% of Americans take some form of dietary supplement every day, and the supplement industry is currently big business, with a gross of over $28 billion. However, unlike either foods or drugs, supplements do not need to be registered or approved by ... ...

Abstract	Over 70% of Americans take some form of dietary supplement every day, and the supplement industry is currently big business, with a gross of over $28 billion. However, unlike either foods or drugs, supplements do not need to be registered or approved by the US Food and Drug Administration (FDA) prior to production or sales. Under the Dietary Supplement Health and Education Act of 1994, the FDA is restricted to adverse report monitoring postmarketing. Despite widespread consumption, there is limited evidence of health benefits related to nutraceutical or supplement use in well-nourished adults. In contrast, a small number of these products have the potential to produce significant toxicity. In addition, patients often do not disclose supplement use to their physicians. Therefore, the risk of adverse drug-supplement interactions is significant. An overview of the major supplement and nutraceutical classes is presented here, together with known toxic effects and the potential for drug interactions.
MeSH term(s)	Animals ; Dietary Supplements/adverse effects ; Drug Interactions/physiology ; Drug-Related Side Effects and Adverse Reactions/etiology ; Humans ; United States ; United States Food and Drug Administration
Language	English
Publishing date	2017-10-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	196587-6
ISSN	1545-4304 ; 0362-1642
ISSN (online)	1545-4304
ISSN	0362-1642
DOI	10.1146/annurev-pharmtox-010617-052844
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Article ; Online: Determination of sex differences in activities of angiotensin-converting enzyme 2 (ACE2) requires an activity assay that doesn't underestimate ACE2.

Pedersen, Kim B / Lazartigues, Eric

American journal of hypertension

2013 Volume 26, Issue 9, Page(s) 1172

MeSH term(s)	Angiotensin I/metabolism ; Animals ; Female ; Kidney Cortex/metabolism ; Kidney Medulla/metabolism ; Male ; Peptide Fragments/metabolism ; Peptidyl-Dipeptidase A/metabolism ; Sex Characteristics
Chemical Substances	Peptide Fragments ; Angiotensin I (9041-90-1) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2013-08-12
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	639383-4
ISSN	1941-7225 ; 1879-1905 ; 0895-7061
ISSN (online)	1941-7225 ; 1879-1905
ISSN	0895-7061
DOI	10.1093/ajh/hpt094
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Article ; Online: Nox4 expression in osteo-progenitors controls bone development in mice during early life.

Chen, Jin-Ran / Lazarenko, Oxana P / Blackburn, Michael L / Chen, Jennifer F / Randolph, Christopher E / Zabaleta, Jovanny / Schroder, Katrin / Pedersen, Kim B / Ronis, Martin J J

Communications biology

2022 Volume 5, Issue 1, Page(s) 583

Abstract: Tightly regulated and cell-specific NADPH-oxidases (Nox) represent one of the major sources of reactive oxygen species (ROS) signaling molecules that are involved in tissue development and stem cell self-renewal. We have characterized the role of Nox4 in ...

Abstract	Tightly regulated and cell-specific NADPH-oxidases (Nox) represent one of the major sources of reactive oxygen species (ROS) signaling molecules that are involved in tissue development and stem cell self-renewal. We have characterized the role of Nox4 in osteo-progenitors during postnatal bone development. Nox4 expression in bone and ROS generation were increased during early osteoblast differentiation and bone development. Stromal osteoblastic cell self-renewal, proliferation and ROS production were significantly lower in samples from whole-body Nox4 knockout mice (Nox4
MeSH term(s)	Animals ; Bone Development/physiology ; Female ; Male ; Mice ; Mice, Knockout ; NADPH Oxidase 4/biosynthesis ; NADPH Oxidase 4/genetics ; NADPH Oxidase 4/metabolism ; Osteogenesis/physiology ; Reactive Oxygen Species/metabolism
Chemical Substances	Reactive Oxygen Species ; NADPH Oxidase 4 (EC 1.6.3.-) ; Nox4 protein, mouse (EC 1.6.3.-)
Language	English
Publishing date	2022-06-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-022-03544-0
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Article ; Online: Chronic Ethanol Feeding in Mice Decreases Expression of Genes for Major Structural Bone Proteins in a Nox4-Independent Manner.

Pedersen, Kim B / Osborn, Michelle L / Robertson, Alex C / Williams, Ashlee E / Watt, James / Denys, Alexandra / Schröder, Katrin / Ronis, Martin J

The Journal of pharmacology and experimental therapeutics

2020 Volume 373, Issue 3, Page(s) 337–346

Abstract: Bone loss in response to alcohol intake has previously been hypothesized to be mediated by excessive production of reactive oxygen species via NADPH oxidase (Nox) enzymes. Nox4 is one of several Nox enzymes expressed in bone. We investigated the role of ... ...

Abstract	Bone loss in response to alcohol intake has previously been hypothesized to be mediated by excessive production of reactive oxygen species via NADPH oxidase (Nox) enzymes. Nox4 is one of several Nox enzymes expressed in bone. We investigated the role of Nox4 in the chondro-osteoblastic lineage of the long bones in mice during normal chow feeding and during chronic ethanol feeding for 90 days. We generated mice with a genotype (
MeSH term(s)	Animals ; Bone Density/drug effects ; Bone Density/genetics ; Bone and Bones/drug effects ; Ethanol/administration & dosage ; Female ; Gene Expression/drug effects ; Genotype ; Male ; Mice ; Mice, Knockout ; NADPH Oxidase 4/genetics ; NADPH Oxidases/genetics ; Osteoblasts/drug effects ; Oxidation-Reduction/drug effects ; Oxidative Stress/drug effects ; Oxidative Stress/genetics ; Reactive Oxygen Species/metabolism
Chemical Substances	Reactive Oxygen Species ; Ethanol (3K9958V90M) ; NADPH Oxidase 4 (EC 1.6.3.-) ; NADPH Oxidases (EC 1.6.3.-) ; Nox4 protein, mouse (EC 1.6.3.-)
Language	English
Publishing date	2020-03-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.119.264374
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Article ; Online: Binge Ethanol Exposure in Mice Represses Expression of Genes Involved in Osteoblast Function and Induces Expression of Genes Involved in Osteoclast Differentiation Independently of Endogenous Catalase.

Denys, Alexandra / Pedersen, Kim B / Watt, James / Norman, Allison R / Osborn, Michelle L / Chen, Jin-Ran / Maimone, Cole / Littleton, Shana / Vasiliou, Vasilis / Ronis, Martin J J

Toxicological sciences : an official journal of the Society of Toxicology

2021 Volume 185, Issue 2, Page(s) 232–245

Abstract: Excessive ethanol consumption is a risk factor for osteopenia. Since a previous study showed that transgenic female mice with overexpression of catalase are partially protected from ethanol-mediated trabecular bone loss, we investigated the role of ... ...

Abstract	Excessive ethanol consumption is a risk factor for osteopenia. Since a previous study showed that transgenic female mice with overexpression of catalase are partially protected from ethanol-mediated trabecular bone loss, we investigated the role of endogenous catalase in skeletal ethanol toxicity comparing catalase knockout to wild-type mice. We hypothesized that catalase depletion would exacerbate ethanol effects. The mice were tested in a newly designed binge ethanol model, in which 12-week-old mice were exposed to 4 consecutive days of gavage with ethanol at 3, 3, 4, and 4.5 g ethanol/kg body weight. Binge ethanol decreased the concentration of serum osteocalcin, a marker of bone formation. The catalase genotype did not affect the osteocalcin levels. RNA sequencing of femoral shaft RNA from males was conducted. Ethanol exposure led to significant downregulation of genes expressed in cells of the osteoblastic lineage with a role in osteoblastic function and collagen synthesis, including the genes encoding major structural bone proteins. Binge ethanol further induced a smaller set of genes with a role in osteoclastic differentiation. Catalase depletion affected genes with expression in erythroblasts and erythrocytes. There was no clear interaction between binge ethanol and the catalase genotype. In an independent experiment, we confirmed that the binge ethanol effects on gene expression were reproducible and occurred throughout the skeleton in males. In conclusion, the binge ethanol exposure, independently of endogenous catalase, reduces expression of genes involved in osteoblastic function and induces expression of genes involved in osteoclast differentiation throughout the skeleton in males.
MeSH term(s)	Animals ; Catalase/genetics ; Catalase/metabolism ; Catalase/pharmacology ; Ethanol/metabolism ; Ethanol/toxicity ; Female ; Male ; Mice ; Mice, Transgenic ; Osteoblasts ; Osteoclasts
Chemical Substances	Ethanol (3K9958V90M) ; Catalase (EC 1.11.1.6)
Language	English
Publishing date	2021-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/kfab135
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Article ; Online: Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet.

Mercer, Kelly E / Pulliam, Casey F / Pedersen, Kim B / Hennings, Leah / Ronis, Martin Jj

Experimental biology and medicine (Maywood, N.J.)

2017 Volume 242, Issue 6, Page(s) 635–644

Abstract: Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain ... ...

Abstract	Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein source on hepatic tumor promotion in a mouse model reflecting aspects of non-alcoholic fatty liver disease (NAFLD). A high-fat liquid diet with casein as the protein source promotes hepatic injury and tumor promotion in diethylnitrosamine-treated mice. Replacing casein with a soy protein isolate led to a pronounced diminishment of tumor promotion and associated hepatic injury and inflammation. The study thus demonstrates that a dietary protein source can have beneficial, preventative effects on hepatic tumor promotion.
MeSH term(s)	Animals ; Blotting, Western ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Gene Expression/drug effects ; Liver/pathology ; Liver Neoplasms/pathology ; Liver Neoplasms/prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/drug therapy ; Non-alcoholic Fatty Liver Disease/pathology ; Soybean Proteins/therapeutic use
Chemical Substances	Soybean Proteins
Language	English
Publishing date	2017-01-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.1177/1535370216685436
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Article: Liver tumorigenesis is promoted by a high saturated fat diet specifically in male mice and is associated with hepatic expression of the proto-oncogene Agap2 and enrichment of the intestinal microbiome with Coprococcus

Pedersen, Kim B. / Pulliam, Casey F. / Patel, Aarshvi / Del, Piero Fabio / Watanabe, Tatiane T. N. / Wankhade, Umesh D. / Shankar, Kartik / Hicks, Chindo / Ronis, Martin J.

Carcinogenesis. 2019 Feb., v. 40, no. 2

2019

Abstract: Liver cancer results in a high degree of mortality, especially among men. As fatty liver disease is a risk factor for development of hepatocellular carcinoma, we investigated the role of dietary fat type in tumor promotion by high-fat diets in mice after ...

Abstract	Liver cancer results in a high degree of mortality, especially among men. As fatty liver disease is a risk factor for development of hepatocellular carcinoma, we investigated the role of dietary fat type in tumor promotion by high-fat diets in mice after initiation with the chemical carcinogen diethyl nitrosamine. Tumor incidence and multiplicity were significantly greater in males than those in females. In males, fat type had complex effects on tumorigenesis. Preneoplastic foci were most prevalent in mice fed a polyunsaturated fat diet enriched in docosahexaenoic acid, whereas carcinomas and large visible liver tumors were significantly greater in mice fed a saturated fat diet made with cocoa butter relative to mice fed mono- or polyunsaturated fats. Different mechanisms thus seemed involved in early and late tumor promotion. The hepatic transcriptome and gut microbiome were assessed for traits associated with tumorigenesis. Hepatic expression of more than 20% of all genes was affected by sex, whereas fat type affected fewer genes. In males, the saturated fat diet induced expression of the proto-oncogene Agap2 and affected the expression of several cytochrome P450 genes, and genes involved in lipid, bile acid and fatty acid metabolism. The gut microbiome had a higher level of genus Akkermansia and a lower level of Firmicutes in females than in males. Males fed saturated fat had an altered microbiome, including an enrichment of the genus Coprococcus. In conclusion, sex and the dietary fat type affect the gut microbiome, the hepatic transcriptome and ultimately hepatic tumor growth.
Keywords	Coprococcus ; bile acids ; carcinogenesis ; carcinogens ; cocoa butter ; cytochrome P-450 ; dietary fat ; docosahexaenoic acid ; fatty acid metabolism ; fatty liver ; hepatoma ; intestinal microorganisms ; liver ; males ; microbiome ; mortality ; proto-oncogenes ; risk factors ; saturated fats ; transcriptome ; unsaturated fats
Language	English
Dates of publication	2019-02
Size	p. 349-359.
Publishing place	Oxford University Press (OUP)
Document type	Article
ZDB-ID	603134-1
ISSN	1460-2180 ; 0143-3334
ISSN (online)	1460-2180
ISSN	0143-3334
DOI	10.1093/carcin/bgy141
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Glucose induces expression of rat pyruvate carboxylase through a carbohydrate response element in the distal gene promoter.

Pedersen, Kim B / Buckley, Rebecca S / Scioneaux, Ray

The Biochemical journal

2010 Volume 426, Issue 2, Page(s) 159–170

Abstract: Pyruvate carboxylase is an enzyme of the so-called pyruvate cycling pathways, which have been proposed to contribute to glucose-stimulated insulin secretion in pancreatic beta-cells. In the rat insulinoma cell line 832/13, transcripts from both the ... ...

Abstract	Pyruvate carboxylase is an enzyme of the so-called pyruvate cycling pathways, which have been proposed to contribute to glucose-stimulated insulin secretion in pancreatic beta-cells. In the rat insulinoma cell line 832/13, transcripts from both the distal and proximal gene promoter for pyruvate carboxylase are up-regulated by glucose, with pyruvate carboxylase being expressed mainly from the distal gene promoter. At position -408 to -392 relative to the transcription start site, the distal gene promoter was found to contain a ChoRE (carbohydrate response element). Its deletion abolishes glucose responsiveness of the promoter, and the sequence can mediate glucose responsiveness to a heterologous gene promoter. ChREBP (carbohydrate response element-binding protein) and its dimerization partner Mlx (Max-like protein X) bind to the ChoRE in vitro. ChREBP further binds to the distal promoter region at a high glucose concentration in situ. The E-box-binding transcription factors USF1/2 (upstream stimulatory factor 1/2) and E2A variant 2 [also known as E47 and TCF3 (transcription factor 3)] can also bind to the ChoRE. Overexpression of E2A diminishes the magnitude of the glucose response from the pyruvate carboxylase ChoRE. This illustrates that competition between ChREBP-Mlx and other factors binding to the ChoRE affects glucose responsiveness. We conclude that a ChoRE in the distal gene promoter contributes to the glucose-mediated expression of pyruvate carboxylase.
MeSH term(s)	Animals ; Base Sequence ; Binding Sites ; Cell Line, Tumor ; Gene Expression Regulation, Enzymologic ; Glucose/metabolism ; Molecular Sequence Data ; Promoter Regions, Genetic ; Protein Binding ; Pyruvate Carboxylase/blood ; Pyruvate Carboxylase/chemistry ; Pyruvate Carboxylase/genetics ; Pyruvate Carboxylase/metabolism ; Rats/genetics ; Rats/metabolism ; Response Elements ; Sequence Deletion ; Transcriptional Activation
Chemical Substances	Pyruvate Carboxylase (EC 6.4.1.1) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2010-02-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2969-5
ISSN	1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online)	1470-8728
ISSN	0006-2936 ; 0306-3275 ; 0264-6021
DOI	10.1042/BJ20091266
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Article ; Online: Skeletal Toxicity of Coplanar Polychlorinated Biphenyl Congener 126 in the Rat Is Aryl Hydrocarbon Receptor Dependent.

Williams, Ashlee E / Watt, James / Robertson, Larry W / Gadupudi, Gopi / Osborn, Michele L / Soares, Michael J / Iqbal, Khursheed / Pedersen, Kim B / Shankar, Kartik / Littleton, Shana / Maimone, Cole / Eti, Nazmin A / Suva, Larry J / Ronis, Martin J J

Toxicological sciences : an official journal of the Society of Toxicology

2020 Volume 175, Issue 1, Page(s) 113–125

Abstract: Epidemiological evidence links polychlorinated biphenyls (PCBs) to skeletal toxicity, however mechanisms whereby PCBs affect bone are poorly studied. In this study, coplanar PCB 126 (5 μmol/kg) or corn oil vehicle was administered to N = 5 and 6 male and ...

Abstract	Epidemiological evidence links polychlorinated biphenyls (PCBs) to skeletal toxicity, however mechanisms whereby PCBs affect bone are poorly studied. In this study, coplanar PCB 126 (5 μmol/kg) or corn oil vehicle was administered to N = 5 and 6 male and female, wild type (WT) or AhR -/- rats via intraperitoneal injection. Animals were sacrificed after 4 weeks. Bone length was measured; bone morphology was assessed by microcomputed tomography and dynamic histomorphometry. Reduced bone length was the only genotype-specific effect and only observed in males (p < .05). WT rats exposed to PCB 126 had reduced serum calcium, and smaller bones with reduced tibial length, cortical area, and medullary area relative to vehicle controls (p < .05). Reduced bone formation rate observed in dynamic histomorphometry was consistent with inhibition of endosteal and periosteal bone growth. The effects of PCB 126 were abolished in AhR -/- rats. Gene expression in bone marrow and shaft were assessed by RNA sequencing. Approximately 75% of the PCB-regulated genes appeared AhR dependent with 89 genes significantly (p < .05) regulated by both PCB 126 and knockout of the AhR gene. Novel targets significantly induced by PCB 126 included Indian hedgehog (Ihh) and connective tissue growth factor (Ctgf/Ccn2), which regulate chondrocyte proliferation and differentiation in the bone growth plate and cell-matrix interactions. These data suggest the toxic effects of PCB 126 on bone are mediated by AhR, which has direct effects on the growth plate and indirect actions related to endocrine disruption. These studies clarify important mechanisms underlying skeletal toxicity of dioxin-like PCBs and highlight potential therapeutic targets.
MeSH term(s)	Animals ; Basic Helix-Loop-Helix Transcription Factors/agonists ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Endocrine Disruptors/toxicity ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Growth Plate/drug effects ; Growth Plate/metabolism ; Growth Plate/pathology ; Liver/drug effects ; Liver/metabolism ; Male ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Polychlorinated Biphenyls/toxicity ; RNA-Seq ; Rats, Sprague-Dawley ; Rats, Transgenic ; Receptors, Aryl Hydrocarbon/agonists ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism ; Signal Transduction ; Tibia/drug effects ; Tibia/metabolism ; Tibia/pathology ; Transcriptome
Chemical Substances	Ahr protein, rat ; Basic Helix-Loop-Helix Transcription Factors ; Endocrine Disruptors ; Gpnmb protein, rat ; Membrane Glycoproteins ; Receptors, Aryl Hydrocarbon ; Polychlorinated Biphenyls (DFC2HB4I0K) ; 3,4,5,3',4'-pentachlorobiphenyl (TSH69IA9XF)
Language	English
Publishing date	2020-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/kfaa030
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