Local in vivo administration of a decoy oligonucleotide targeting NF-kappaB induces apoptosis of osteoclasts after application of orthodontic forces to rat teeth.
In this study, we report the in vivo effects of a decoy oligonucleotide targeting the nuclear factor kappaB (NF-kappaB) on osteoclasts during forced orthodontic tooth movement in rats. Wistar rats were subjected to orthodontic forces, in the absence or presence of treatment with a decoy molecule mimicking a nonsymmetric NF-kappaB binding site (5'-CGC TGG GGA CTT TCC ACG G-3'). TUNEL staining of fragmented DNA revealed that treatment with NF-kappaB decoy but not with scramble double-stranded oligodeoxynucleotides (ODN) induced a high level of osteoclast apoptosis in vivo. Immunohystochemical analysis for death receptor Fas revealed strong positivity only in samples treated with NF-kappaB decoys, demonstrating that osteoclasts are sensitive to death induction via Fas signaling. Induction of apoptosis in osteoclasts could be a strategy for treatment of excessive osteoclast activity in pathologic conditions such as osteoporosis, peri-articular osteolysis, inflammatory arthritis, Paget's syndrome and tumour-associated osteolytic metastases.
Penolazzi
Letizia
L
ER-GenTech, Department of Biochemistry and Molecular Biology, Molecular Biology Section, University of Ferrara, Ferrara, Italy.
Magri
Eros
E
Lambertini
Elisabetta
E
Calò
Girolamo
G
Cozzani
Mauro
M
Siciliani
Giuseppe
G
Piva
Roberta
R
Gambari
Roberto
R
D000818:Animals; D017209:Apoptosis; D004247:DNA / Q000032:analysis; D020287:In Situ Nick-End Labeling; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D010010:Osteoclasts / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D014070:Tooth / Q000166:cytology / Q000187:drug effects*
C468119:NF-kappaB decoy; D009838:Oligodeoxyribonucleotides; D004247:DNA