Induction of apoptosis of osteoclasts by targeting transcription factors with decoy molecules.
We review the effects of two transcription factor decoy oligonucleotides on apoptosis of human osteoclasts (OCs). The first decoy molecule was designed to inhibit nuclear factor kappa-B (NF-kappaB) binding to target sequence, the second to increase estrogen receptor (ER) alpha expression. We found that both decoy molecules are potent inducers of apoptosis of human OCs, associated with increase of caspase 3 activity and decrease of interleukin 6 expression. In addition, we provide evidence indicating that these oligonucleotides are active in vivo in inducing OCs apoptosis. Because OCs are essential for skeletal development and remodeling throughout the life of animal and man, the approach described is of potential clinical importance.
Piva
Roberta
R
Department of Biochemistry and Molecular Biology, Section of Molecular Biology, Università degli Studi di Ferrara, Via Fossato di Mortara 74, 44100 Ferrara, Italy.
Penolazzi
Letizia
L
Zennaro
Margherita
M
Bianchini
Ercolina
E
Magri
Eros
E
Borgatti
Monica
M
Lampronti
Ilaria
I
Lambertini
Elisabetta
E
Tavanti
Elisa
E
Gambari
Roberto
R
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D032701:Biomimetics; D016503:Drug Delivery Systems; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors