GENE SILENCING PART II 

Minerva Biotecnologica 2008 June;20(2):69-77

Copyright © 2008 EDIZIONI MINERVA MEDICA

language: English

Modulation of expression of specific transcription factors involved in the bone microenvironment

Lambertini E., Penolazzi L., Tavanti E., Pocaterra B., Schincaglia G. P., Torreggiani E., Franceschetti T., Vecchiattini R., Gambari R., Piva R.

Molecular Biology Section Department of Biochemistry and Molecular Biology University of Ferrara, Ferrara, Italy

The skeletal system functions and maintains itself thanks to the communication between cells of diverse origins such as osteoclasts (OCs) and osteoblasts (OBs). In bone remodelling, bone resorption by OCs is followed by osteoblastic bone formation, so that resorbed lacunae are filled to the original level by OBs. In this respect many growth factors and transcription factors are involved in both in OBs and in OCs differentiation. Here, the roles of NF-kB, NFATc1, estrogen receptor a, and Runx2, that are critical regulators of osteclastogenesis and OB differentiation, are discussed. In particular, the effects of “decoy” oligodeoxynucleotides (ODN) against NF-kB and NFATc1 on OCs activation and regulation both in vitro and in vivo are examined. The transcription factor (TF) “decoy” technology is based on the employment of synthetic double-stranded ODN containing a cis-element with high affinity for a target TF. In the cells transfected with these ODN the authentic cis-trans interactions are attenuated, the TF from the endogenous cis elements is removed and a specific modulation of gene expression is obtained. In addition, the siRNA approach was used to analyse the role of Runx2 transcription factor in the regulation of ERa gene expression which is a key regulator of bone homeostasis.