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.