NFkappaB decoy oligodeoxynucleotides ameliorates osteoporosis through inhibition of activation and differentiation of osteoclasts

Gene Therapy
H ShimizuRyuichi Morishita

Abstract

The transcription factor, nuclear factor-kappa B (NFkappaB), is believed to play a pivotal role in osteoclast formation. In this study, we focused on NFkappaB decoy oligodeoxynucleotides (ODN) as a new therapeutic strategy to attenuate osteoporosis. Tartrate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts formed in mononuclear cells including osteoclast precursors from neonatal rabbit bone marrow were increased in the presence of 1,25-dihydroxyvitamin D3, whereas transfection of NFkappaB decoy ODN decreased the number of TRAP-positive cells and attenuated RANKL and M-CSF-induced osteoclast formation. NFkappaB decoy ODN also inhibited the activity of osteoclasts, as assessed by pit formation. In rat ovariectomized model of estrogen deficiency, continuous administration of NFkappaB decoy ODN attenuated the increase of TRAP activity, accompanied by a significant increase in calcium concentration in tibia and femur and decrease in urinary deoxypyridinoline. In additional osteoporosis model using vitamin C-deficient rat, inhibition of NFkappaB by decoy ODN dramatically improved the bone length, weight, density as assessed by dual-energy X-ray absorptiometry. Overall, inhibition of NFkappaB by decoy strategy preve...Continue Reading

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Citations

Jul 11, 2009·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hideo ShimizuRyuichi Morishita
Sep 2, 2011·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hideo ShimizuRyuichi Morishita
Apr 29, 2015·Molecular Therapy. Nucleic Acids·David PorcianiGiovanni Signore
Feb 8, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hideo ShimizuRyuichi Morishita

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