Delayed osteoblastic differentiation and bone development in Cx43 knockout mice.

Abstract:

:GJA1 gene (Connexin43, also known as Cx43) is the most abundant gap junction protein isoform in animal cells and is associated with bone development in embryos. The objective of the present work was to evaluate in vivo osteal development in GJA1-deficient fetal mice through determination of the histological and molecular alterations induced by partial or total deletion of the GJA1 gene. Heterozygous C57BL/6 mice (HT) harboring a null mutation of the GJA1 gene were mated, and pregnant females were submitted to euthanasia and Caesarean section from 12.5 to 19.5 days post coitum (dpc). HT (GJA1(+/-)) and homozygous (GJA1(-/- )) knockout (KO) mutants and wild-type (WT) fetuses were identified by polymerase chain reaction (PCR), and development curves were constructed on the basis of fetus weight and crown-rump length. Histopathological, histochemical, and real-time PCR analyses were performed in order to assess the expression of markers associated with bone development, namely, osteocalcin, osteopontin, alkaline phosphatase, RUNX2, GJA1, GJC1 (Cx45), and GJA3 (Cx46). HT and KO fetuses exhibited delays in the differentiation of osteoblasts and, consequently, in bone development in comparison with the WT group. Additionally, less deposition of mineralized and osteoid matrix was observed in GJA1-deficient fetuses. Bone development in KO fetuses was delayed through the moment of birth, but in HT animals the delay only extended until 17.5 dpc, following which development was normalized. The expression of genes coding for osteocalcin, osteopontin, alkaline phosphatise, and RUNX2 were also delayed in GJA1-deficient fetuses. Animals that exhibited a lower expression of GJA1 presented delayed expression of the GJC1 and GJA3 genes and their corresponding protein products in the bone tissue. The results of the present study contribute to our understanding of the function of GJA1 during bone development and suggest that GJC1 could play a role in restoring intercellular communication in GJA1-deficient mice.

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

Chaible LM,Sanches DS,Cogliati B,Mennecier G,Dagli ML

doi

10.1177/0192623311422075

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

1046-55

issue

7

eissn

0192-6233

issn

1533-1601

pii

0192623311422075

journal_volume

39

pub_type

杂志文章
  • The utility of immunohistochemistry for the identification of hematopoietic and lymphoid cells in normal tissues and interpretation of proliferative and inflammatory lesions of mice and rats.

    abstract::Expression of antigens in cells and tissues can be readily studied immunohistochemically with the use of antibodies. A panel of antibodies to cell-specific markers can be used to diagnose lesions, including tumors, in the hematopoietic and lymphoid systems. This review discusses the use of readily available antibodies...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/0192623311430695

    authors: Rehg JE,Bush D,Ward JM

    更新日期:2012-01-01 00:00:00

  • A communicating intestinal duplication in a Sprague-Dawley rat.

    abstract::Duplications of the gastrointestinal tract are exceedingly rare in laboratory animals. We report a case of a communicating intestinal duplication in a 17-wk-old Sprague-Dawley (SD) rat. The duplication was present in the mesenteric border of the ileum, and both proximal and distal ends were communicated with the lumen...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339802600216

    authors: Elangbam CS,Clevidence KJ,Jackson CB,Holson JF

    更新日期:1998-03-01 00:00:00

  • Evaluation of clinical pathology data: correlating changes with other study data.

    abstract::During the conduct of in vivo toxicology studies, in-life, clinical pathology, and anatomic pathology parameters are collected and interpreted. These sets of parameters are evaluated in an integrative manner to determine the overall toxicity of a test article. For clinical pathology parameters, the inherent variabilit...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623314555340

    authors: Everds NE

    更新日期:2015-01-01 00:00:00

  • The value of historical control data-scientific advantages for pathologists, industry and agencies.

    abstract::Historical control tumor data are useful in the interpretation of long-term rodent carcinogenicity bioassays, especially to assess the occurrence of rare tumors and marginally increased tumor incidences. The major prerequisites to compare historical control data with studies under evaluation are the validity and consi...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1080/01926230252824743

    authors: Deschl U,Kittel B,Rittinghausen S,Morawietz G,Kohler M,Mohr U,Keenan C

    更新日期:2002-01-01 00:00:00

  • Enzyme histochemical changes in an acutely induced renal papillary necrosis.

    abstract::Enzyme histochemistry was assessed in semi-thin glycolmethacrylate sections after 100 mg/kg 2-bromoethanamine (BEA) hydrobromide had been given ip to male Wistar rats to induce renal papillary necrosis. Changes in the proximal tubular marker enzymes alkaline phosphatase (Alk Phos), gamma-glutamytranspeptidase (GGT) an...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339001800106

    authors: Gregg NJ,Courtauld EA,Bach PH

    更新日期:1990-01-01 00:00:00

  • Spontaneous mesotheliomas in Fischer rats--a histological and electron microscopic study.

    abstract::Seventeen mesotheliomas from 395 untreated male Fischer 344/DuCrj rats were studied by light and electron microscopy to define the morphological characteristics of the tumors. In 16 out of 17 rats, mesotheliomas were observed in the abdominal and/or scrotal sac, and the other one was localized on the pleura. Grossly, ...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338701500205

    authors: Tanigawa H,Onodera H,Maekawa A

    更新日期:1987-01-01 00:00:00

  • Introduction to Special Issue on Ocular Pathology and Drug Development.

    abstract::Dysfunction of the visual system remains a leading cause of human disability worldwide. Preclinical studies are a key component of efforts to develop drugs and devices to ameliorate visual impairment. Although new opportunities for the delivery of targeted ocular therapeutics have been created, clinical success has be...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623320986558

    authors: Ramos MF,Schafer KA,Sorden SD

    更新日期:2021-01-05 00:00:00

  • Immunohistochemical study of rat renal interstitial fibrosis induced by repeated injection of cisplatin, with special reference to the kinetics of macrophages and myofibroblasts.

    abstract::Progressive renal interstitial fibrosis occurs following tissue injury, resulting in chronic renal failure. In the fibrogenesis, macrophages are speculated to induce myofibroblasts producing matrix protein. The kinetics of these cells in renal fibrosis induced in rats by repeated injection of cisplatin (CDDP) (2 mg/kg...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339602400208

    authors: Yamate J,Ishida A,Tsujino K,Tatsumi M,Nakatsuji S,Kuwamura M,Kotani T,Sakuma S

    更新日期:1996-03-01 00:00:00

  • Dose-response relationship of diethylnitrosamine-initiated tumors in neonatal balb/c mice: effect of phenobarbital promotion.

    abstract::The dose-response of diethylnitrosamine (DENA) initiation of hepatocarcinogenesis was determined in infant Balb/c male mice with and without subsequent phenobarbital treatment. Male Balb/c mice received a single intraperitoneal injection of DENA (0, 2.5, 10.0, 25.0 or 50.0 micrograms/gbw) in saline on day 15 of age. N...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338801600310

    authors: Klaunig JE,Pereira MA,Ruch RJ,Weghorst CM

    更新日期:1988-01-01 00:00:00

  • The syrian hamster embryo (SHE) cell transformation assay: review of the methods and results.

    abstract::The Syrian hamster embryo (SHE) cell-transformation assay represents a short-term in vitro assay capable of predicting rodent carcinogenicity of chemicals with a high degree of concordance (LeBoeuf et al [1996]. Mutat Res 356: 85-127). The SHE assay models the earliest identifiable stage in carcinogenicity, morphologi...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/019262301753178546

    authors: Mauthe RJ,Gibson DP,Bunch RT,Custer L

    更新日期:2001-01-01 00:00:00

  • The use of quantitative histological and molecular data for risk assessment and biologically based model development.

    abstract::In organs with diverse cell populations, it is not uncommon for one type of cell to respond while others are spared. Even in an organ with common cell types, such as hepatocytes within the liver, the population of cells may respond with different sensitivities for injury or for biochemical responses to toxicants. In t...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1080/01926230252824789

    authors: Andersen ME

    更新日期:2002-01-01 00:00:00

  • Untargeted metabolomic profiling as an evaluative tool of fenofibrate-induced toxicology in Fischer 344 male rats.

    abstract::Peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists such as fenofibrate are used to treat dyslipidemia. Although fenofibrate is considered safe in humans, it is known to cause hepatocarcinogenesis in rodents. To evaluate untargeted metabolic profiling as a tool for gaining insight into the underlying...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623309336152

    authors: Ohta T,Masutomi N,Tsutsui N,Sakairi T,Mitchell M,Milburn MV,Ryals JA,Beebe KD,Guo L

    更新日期:2009-06-01 00:00:00

  • Cytokeratin expression patterns in the rat respiratory tract as markers of epithelial differentiation in inhalation toxicology. II. Changes in cytokeratin expression patterns following 8-day exposure to room-aged cigarette sidestream smoke.

    abstract::The expression of specific cytokeratin (CK) polypeptide patterns is a sensitive marker of the cytoskeletal differentiation of epithelial cells. We developed an immunohistochemical method to assess CK expression patterns in the rat respiratory tract using serial paraffin-embedded sections from the nasal cavity, trachea...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339802600308

    authors: Schlage WK,Bülles H,Friedrichs D,Kuhn M,Teredesai A,Terpstra PM

    更新日期:1998-05-01 00:00:00

  • The genetics of cancer susceptibility: from mouse to man.

    abstract::Cancer affects approximately 1 in 3 individuals. An individual's susceptibility to cancer is partly determined by environmental exposures and by the combination of inherited cancer susceptibility and resistance genes. Initial mapping of these low penetrance cancer susceptibility genes has been done in the mouse becaus...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1080/01926230490424716

    authors: Ewart-Toland A,Balmain A

    更新日期:2004-03-01 00:00:00

  • Correlation of toxicity and pharmacokinetic properties of a phosphorothioate oligonucleotide designed to inhibit ICAM-1.

    abstract::ISIS 2302 is a phosphorothioate oligodeoxynucleotide with a sequence complementary to the mRNA of human intercellular adhesion molecule 1 (ICAM-1). Hybridization of ISIS 2302 to the mRNA inhibits expression of the ICAM-1 protein in response to inflammatory stimuli. A murine active antisense oligonucleotide, ISIS 3082,...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/019262339902700117

    authors: Henry SP,Templin MV,Gillett N,Rojko J,Levin AA

    更新日期:1999-01-01 00:00:00

  • Regulatory Forum Opinion Piece*: Effective Sectioning of Spinal Cord during Regulatory-type Nonclinical Toxicity Studies.

    abstract::Regulatory guidelines for nonclinical neurotoxicity testing require spinal cord evaluation but do not specify a trimming scheme. The Society of Toxicologic Pathology (STP) "best practices" for nervous system sampling during nonclinical general toxicity studies recommend that spinal cord be assessed in both longitudina...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623317720120

    authors: Bolon B

    更新日期:2017-07-01 00:00:00

  • Metastasis to the F344 Rat Pancreas from Lung Cancer Induced by 4-(Methylnitrosamino)- 1-(3-pyridyl)-1-butanone and Enantiomers of Its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)- 1-butanol, Constituents of Tobacco Products.

    abstract::Lung cancer is the most common cause of cancer-related deaths in humans worldwide. There is strong evidence that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) play an important role in carcinogenesis caused ...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623317751573

    authors: Kovi RC,Johnson CS,Balbo S,Hecht SS,O'Sullivan MG

    更新日期:2018-02-01 00:00:00

  • Epididymal sperm granuloma induced by chronic administration of 2-methylimidazole in B6C3F1 mice.

    abstract::Two-year mouse and rat bioassay studies of 2-methylimidazole (2-MI) conducted by the National Toxicology Program revealed that epididymal sperm granuloma(SG)s occurred only in male B6C3F1 mice in a dose-related manner. The present study characterized 2-MI-induced SGs in these epididymides. Groups of 50 male B6C3F1 mic...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230590922866

    authors: Tani Y,Foster PM,Sills RC,Chan PC,Peddada SD,Nyska A

    更新日期:2005-01-01 00:00:00

  • Effect of alternate-day hydrocortisone therapy on the immunologically immature rat. II: Changes in T- and B-cell areas in spleen.

    abstract::The histologic effect of 400 mg/M2/day of hydrocortisone, given alternatively from day 7 to day 19 after birth, was studied on the spleen of the immunologically immature rat. Two days after the cessation of treatment, the periarteriolar lymphatic sheaths were found to be largely depleted of small lymphocytes. Immunope...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339302100406

    authors: el Fouhil AF,Iskander FA,Turkall RM

    更新日期:1993-01-01 00:00:00

  • Non-reversibility of vinyl chloride carcinogenesis in rodents.

    abstract::A review of the data obtained from various studies on carcinogenicity of vinyl chloride (VC) in rodents, particularly on the effect of dose, age, duration of exposure and potential reversibility of lesions, revealed that vinyl chloride-induced carcinogenicity in rodents was dose and time related; no recovery occurred ...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338301100210

    authors: Bhandari JC

    更新日期:1983-01-01 00:00:00

  • A pilot study in adult rhesus monkeys (M. mulatta) treated with Aroclor 1254 for two years.

    abstract::Aroclor 1254, at a dose level of 280 micrograms/kg body weight equivalent to 200 micrograms/kg/day, was given 5 days per week to rhesus monkeys over a 27 to 28 month period. Terminal clinical signs of varying severity included fingernail detachment, exuberant nail beds, weight loss, stomatitis and normocytic anemia. A...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338601400101

    authors: Tryphonas L,Arnold DL,Zawidzka Z,Mes J,Charbonneau S,Wong J

    更新日期:1986-01-01 00:00:00

  • Approaches to the identification and recording of nasal lesions in toxicology studies.

    abstract::The identification, recording, and interpretation of nasal lesions can be a difficult task in toxicology studies. The objective of this article is to provide some guidelines for approaches to nasal toxicologic pathology, based on the author's experience and information available in the published literature. Identifica...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/0192623391019004-103

    authors: Morgan KT

    更新日期:1991-01-01 00:00:00

  • Postnatal development of the testis in the rat: morphologic study and correlation of morphology to neuroendocrine parameters.

    abstract::Histopathologic examination of the testis from juvenile rats is often necessary to characterize the safety of new drugs for pediatric use and is a required end point in male pubertal development and thyroid function assays. To aid in evaluation and interpretation of the immature testis, the characteristic histologic f...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623314547279

    authors: Picut CA,Remick AK,de Rijk EP,Simons ML,Stump DG,Parker GA

    更新日期:2015-04-01 00:00:00

  • Biomarkers and mechanisms of drug-induced vascular injury in non-rodents.

    abstract::In preclinical safety studies, drug-induced vascular injury can negatively impact candidate-drug selection because there are no obvious diagnostic markers for monitoring this pathology preclinically or clinically. Furthermore, our current understanding of the pathogenesis of this lesion is limited. While vasodilatatio...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1080/01926230500512076

    authors: Louden C,Brott D,Katein A,Kelly T,Gould S,Jones H,Betton G,Valetin JP,Richardson RJ

    更新日期:2006-01-01 00:00:00

  • Toxicity profiles in rats treated with tumorigenic and nontumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.

    abstract::Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have a common mode of antifungal action through inhibition of ergosterol biosynthesis. Some members of this class have been shown to be hepatotoxic and will induce mouse hepatocellular tumors and/or rat thyroid fol...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230601047808

    authors: Wolf DC,Allen JW,George MH,Hester SD,Sun G,Moore T,Thai SF,Delker D,Winkfield E,Leavitt S,Nelson G,Roop BC,Jones C,Thibodeaux J,Nesnow S

    更新日期:2006-01-01 00:00:00

  • Scanning and transmission electron microscopic observations of the acute morphological response of the mouse urinary bladder to 4-ethylsulfonylnaphthalene-1-sulfonamide.

    abstract::A total of 75 BALB/cStCrlfC3H/Nctr male weanling mice were administered either 0 or 250 ppm of 4 ethylsulfonylnaphthalene-1-sulfonamide (ENS) in the diet for periods up to 14 days to evaluate the early morphological changes of the transitional epithelium of the urinary bladder with scanning (SEM) and transmission (TEM...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338601400302

    authors: Frith CH,Ayres PH,Shinohara Y,West R

    更新日期:1986-01-01 00:00:00

  • Liver tumor-promoting effect of beta-naphthoflavone, a strong CYP 1A1/2 inducer, and the relationship between CYP 1A1/2 induction and Cx32 decrease in its hepatocarcinogenesis in the rat.

    abstract::Interrelationships among induction of cytochrome P-450 (CYP) 1A1/2, decrease in connexin 32 (Cx32), and liver tumor-promoting activity by beta-naphthoflavone (BNF) in the promotion stage were examined in a 2-stage liver carcinogenesis model. A total of 20 male Fischer 344 rats were initiated with a single intraperiton...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262330002800406

    authors: Shoda T,Mitsumori K,Onodera H,Toyoda K,Uneyama C,Takada K,Hirose M

    更新日期:2000-07-01 00:00:00

  • Ocular Medical Devices: Histologic Technique and Histopathologic Evaluation of the Biocompatibility and Performance.

    abstract::Ocular medical devices (MDs) represent a very wide and promising field of human ophthalmology. In preclinical studies evaluating the safety and/or performance of these ocular MDs, the choice of histologic technique and the focus of the histopathologic evaluation method should take into consideration the following aspe...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/0192623318813533

    authors: Drevon-Gaillot E

    更新日期:2019-04-01 00:00:00

  • Toxicokinetics/toxicodynamic correlations: goals, methods, and limitations.

    abstract::Toxicokinetic (TK) studies are the basis for demonstrating dose-related drug exposure in animals and for ensuring that drug exposure is substantially greater in animals than that expected in humans at therapeutic doses. The usefulness of TK studies can be further enhanced by correlating TK parameters with relevant tox...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/019262339502300209

    authors: Batra VK

    更新日期:1995-03-01 00:00:00

  • An Immunopathological Evaluation of the Porcine Cholecyst Matrix as a Muscle Repair Graft in a Male Rat Abdominal Wall Defect Model.

    abstract::With the increasing use of animal-based biomaterials for regenerative medical applications, the need for their safety assessment is paramount. A porcine cholecyst-derived scaffold (CDS), intended as a muscle repair graft, prepared by a nondetergent/enzymatic method was engrafted in a rat abdominal wall defect model. H...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623317752894

    authors: Balakrishnan-Nair DK,Nair ND,Venugopal SK,Das VN,George S,Abraham MJ,Eassow S,Alison MR,Sainulabdeen A,Anilkumar TV

    更新日期:2018-02-01 00:00:00