Kota, Venkata Bhanu Prakash (2012) Identification of the role of a novel conserved leucine Zipper – containing protein in osteogenic differentiation of mesenchymal stem cells. [Tesi di dottorato] (Unpublished)

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Item Type: Tesi di dottorato
Lingua: English
Title: Identification of the role of a novel conserved leucine Zipper – containing protein in osteogenic differentiation of mesenchymal stem cells
Creators:
CreatorsEmail
Kota, Venkata Bhanu Prakashbhanu.kota1@gmail.com
Date: 1 February 2012
Number of Pages: 130
Institution: Università degli Studi di Napoli Federico II
Istituzioni (extra): CEINGE  Biotecnologie Avanzate
Scuola di dottorato: SEMM – European School of Molecular Medicine
Dottorato: PhD in Molecular Medicine (Molecular Oncology or Human Genetics)
Ciclo di dottorato: 23
Coordinatore del Corso di dottorato:
nomeemail
Salvatore, Francescosalvator@unina.it
Tutor:
nomeemail
Pastore, Luciopastore@ceinge.unina.it
Russo, Tommasotommaso.russo@unina.it
Smaldone, Silviasilvia.smaldone@mssm.edu
Date: 1 February 2012
Number of Pages: 130
Uncontrolled Keywords: OB3, Creb3, Osteogenesis
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/03 - Genetica medica
Additional Information: Ciclo V/XXIII, Curriculum Human Genetics
Date Deposited: 15 Feb 2012 14:36
Last Modified: 12 Jan 2015 12:27
URI: http://www.fedoa.unina.it/id/eprint/9006

Abstract

ABSTRACT Adult bone marrow mesenchymal stem cells have the ability to differentiate into different cell types such as osteoblasts, adipocytes, chondrocytes, myoblasts, neural cells etc. The multipotency of mesenchymal stem cells, its easy isolation and culture as wells as their high ex vivo expansion potential make these cells to be exploited for therapeutic purpose. Despite enormous data available at molecular and cellular levels, it is evident that number of fundamental queries regarding molecular and cellular mechanisms needs to be elucidated. The present study is aimed at understanding differentiation of osteoblasts from mesenchymal stem cells (MSC) by certain candidate genes. shRNA based library screening was performed in our laboratory to silence specific mRNA that interfere with osteoblasts differentiation from MSC. shRNA library led to the identification of several candidate genes of known as well as unknown function. We focused our studies on candidate genes whose function is unknown and termed as osteoblasts inducer (ObI/OB). Current study is limited to understand a particular gene termed as ‘OB3’ in succession to our previously identified and characterized genes. OB3 gene identified during shRNA library screening was validated in both bone marrow stromal cell lines as well as murine primary mesenchymal stem cells. Its expression during osteoblasts differentiation has to been elucidated and its silencing effects on bone markers has been shown. We have by microarray few targets that are repressed upon OB3 silencing and involved in osteoblasts differentiation. Moreover, OB3 protein undergoes proteasome degradation and we have attempted if not completely to show that OB3 degradation is mediated through ubiquitin-proteasome. We have identified Creb3 as a partner of OB3 and have attempted to show creb3 silencing during osteoblasts differentiation. Furthermore overexpression of both OB3 and Creb3 independently delay osteoblasts differentiation. Attempts to identify the molecular mechanisms through which these two candidate genes are involved in osteoblasts differentiation is being explored.

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