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

Gene Therapy volume 13, pages 933–941 (2006)Cite this article

Abstract

The transcription factor, nuclear factor-kappa B (NFκB), is believed to play a pivotal role in osteoclast formation. In this study, we focused on NFκB 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 NFκB decoy ODN decreased the number of TRAP-positive cells and attenuated RANKL and M-CSF-induced osteoclast formation. NFκB decoy ODN also inhibited the activity of osteoclasts, as assessed by pit formation. In rat overiectomized model of estrogen deficiency, continuous administration of NFκB 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 NFκB by decoy ODN dramatically improved the bone length, weight, density as assessed by dual-energy X-ray absorptiometry. Overall, inhibition of NFκB by decoy strategy prevented osteoporosis through the inhibition of bone resorption. Targeting of NFκB might be potential therapy in various bone metabolic diseases.

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Acknowledgements

We wish to thank Miss C Kato, N Yasumasa and R Hanayama for their helpful job. This work was partially supported by a Grant-in-Aid from the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), the Organization for Pharmaceutical Safety and Research, a Grant-in-Aid from The Ministry of Public Health and Welfare, a Grant-in-Aid from Japan Promotion of Science, and through Special Coordination Funds of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government.

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Authors and Affiliations

  1. Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

    H Shimizu, H Nakagami & R Morishita

  2. Division of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Osaka, Japan

    H Shimizu, H Nakagami & T Ogihara

  3. Division of Gene Therapy Science, Osaka University Graduate School of Medicine, Osaka, Japan

    H Nakagami & Y Kaneda

  4. Department of Food Science and Nutrition, Nara Women's University, Nara, Japan

    I Tsukamoto

  5. Department of Oral and Maxillofacial Surgery, Osaka Dental University, Osaka, Japan

    S Morita

  6. Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Y Kunugiza, T Tomita & H Yoshikawa

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  1. H Shimizu
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Correspondence to R Morishita.

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Shimizu, H., Nakagami, H., Tsukamoto, I. et al. NFκB decoy oligodeoxynucleotides ameliorates osteoporosis through inhibition of activation and differentiation of osteoclasts. Gene Ther 13, 933–941 (2006). https://doi.org/10.1038/sj.gt.3302711

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  • DOI: https://doi.org/10.1038/sj.gt.3302711

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