Extracellular Matrix Proteins

Publication Title: 
Journal of Endodontics

INTRODUCTION: Dental pulp stem cells (DPSCs) have received much attention as a promising population of stem cells in regenerative endodontics. Securing a good blood supply during regeneration is a challenging task because of the constricted apical canal opening, which allows only a limited blood supply. The aim of this study was to investigate any potential synergistic effects of dental pulp stem cells and endothelial cells (ECs) on osteo-/odontogenic and angiogenic differentiation in vitro.

Author(s): 
Dissanayaka, Waruna Lakmal
Zhan, Xuan
Zhang, Chengfei
Hargreaves, Kenneth M.
Jin, Lijian
Tong, Edith H. Y.
Publication Title: 
Nucleic Acids Research

Reln mRNA and protein levels are reduced by approximately 50% in various cortical structures of post-mortem brain from patients diagnosed with schizophrenia or bipolar illness with psychosis. To study mechanisms responsible for this down-regulation, we have analyzed the promoter of the human reelin gene. We show that the reelin promoter directs expression of a reporter construct in multiple human cell types: neuroblastoma cells (SHSY5Y), neuronal precursor cells (NT2), differentiated neurons (hNT) and hepatoma cells (HepG2).

Author(s): 
Chen, Ying
Sharma, Rajiv P.
Costa, Robert H.
Costa, Erminio
Grayson, Dennis R.
Publication Title: 
Schizophrenia Research

Covalent modifications of DNA and its surrounding chromatin constitute an essential and powerful regulatory mechanism for gene transcription. Epigenetics is the study of this regulatory system. There is now strong albeit indirect evidence that epigenetic mechanisms contribute to the pathophysiology of schizophrenia. Furthermore, the discovery that valproic acid, a widely used psychotropic, has powerful epigenetic effects in clinically relevant concentrations suggests new therapeutic possibilities, i.e., drugs that act on chromatin structure.

Author(s): 
Sharma, Rajiv P.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

The polygenic nature of complex psychiatric disorders suggests a common pathway that may be involved in the down-regulation of multiple genes through an epigenetic mechanism. To investigate the role of methylation in down-regulating the expression of mRNAs that may be associated with the schizophrenia phenotype, we have adopted a cell-culture model amenable to this line of investigation.

Author(s): 
Noh, Jai Sung
Sharma, Rajiv P.
Veldic, Marin
Salvacion, Alain A.
Jia, Xiaomei
Chen, Ying
Costa, Erminio
Guidotti, Alessandro
Grayson, Dennis R.
Publication Title: 
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics

DNA methylation changes could provide a mechanism for DNA plasticity and dynamism for short-term adaptation, enabling a type of cell memory to register cellular history under different environmental conditions. Some environmental insults may also result in pathological methylation with corresponding alteration of gene expression patterns.

Author(s): 
Abdolmaleky, Hamid Mostafavi
Cheng, Kuang-hung
Russo, Andrea
Smith, Cassandra L.
Faraone, Stephen V.
Wilcox, Marsha
Shafa, Rahim
Glatt, Stephen J.
Nguyen, Giang
Ponte, Joe F.
Thiagalingam, Sam
Tsuang, Ming T.
Publication Title: 
American Journal of Pharmacogenomics: Genomics-Related Research in Drug Development and Clinical Practice

No specific gene has been identified for any major psychiatric disorder, including schizophrenia, in spite of strong evidence supporting a genetic basis for these complex and devastating disorders. There are several likely reasons for this failure, ranging from poor study design with low statistical power to genetic mechanisms such as polygenic inheritance, epigenetic interactions, and pleiotropy. Most study designs currently in use are inadequate to uncover these mechanisms.

Author(s): 
Abdolmaleky, Hamid M.
Thiagalingam, Sam
Wilcox, Marsha
Publication Title: 
Pharmacology & Therapeutics

A recent report suggests that the down-regulation of reelin and glutamic acid decarboxylase (GAD(67)) mRNAs represents 2 of the more consistent findings thus far described in post-mortem material from schizophrenia (SZ) patients [reviewed in. Neurochemical markers for schizophrenia, bipolar disorder amd major depression in postmortem brains. Biol Psychiatry 57, 252-260]. To study mechanisms responsible for this down-regulation, we have analyzed the promoter of the human reelin gene.

Author(s): 
Grayson, Dennis R.
Chen, Ying
Costa, Erminio
Dong, Erbo
Guidotti, Alessandro
Kundakovic, Marija
Sharma, Rajiv P.
Publication Title: 
Molecular Pharmacology

Reelin and glutamic acid decarboxylase 67 (GAD67) mRNAs and protein levels are substantially reduced in postmortem brains of patients with schizophrenia. Increasing evidence suggests that the observed down-regulation of reelin and GAD67 gene expression may be caused by dysfunction of the epigenetic regulatory mechanisms operative in cortical GABAergic interneurons.

Author(s): 
Kundakovic, Marija
Chen, Ying
Costa, Erminio
Grayson, Dennis R.
Publication Title: 
Clinical Endocrinology

OBJECTIVE: The pathogenesis of idiopathic hypogonadotrophic hypogonadism (IHH) is mostly unclear. We characterized the clinical findings and molecular analysis of GnRHR and KAL1 genes in 26 Brazilian males with IHH with and without hyposmia/anosmia. Design Clinical assessment was performed for endocrine status, olfactory structure and function, renal lesion, and mirror movement. The diagnosis of Kallmann syndrome (KS) included HH and the clinical complaint of hyposmia/anosmia or decreased olfactory acuity obtained by the Smell Identification Test (SIT).

Author(s): 
Versiani, Beatriz R.
Trarbach, Ericka
Koenigkam-Santos, Marcel
Dos Santos, Antonio Carlos
Elias, Lucila L. K.
Moreira, Ayrton C.
Latronico, Ana Claudia
de Castro, Margaret
Publication Title: 
Schizophrenia Research

In the cerebral prefrontal cortex (PFC), DNA-methyltransferase 1 (DNMT1), the enzyme that catalyzes the methylation of cytosine at carbon atoms in position 5 in CpG dinucleotides, is expressed selectively in GABAergic neurons and is upregulated in layers I and II of schizophrenia (SZ) and bipolar disorder patients with psychosis (BDP).

Author(s): 
Veldic, Marin
Kadriu, Bashkim
Maloku, Ekrem
Agis-Balboa, Roberto C.
Guidotti, Alessandro
Davis, John M.
Costa, Erminio

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