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Heme oxygenase-1 modulates degeneration of the intervertebral disc after puncture in Bach 1 deficient mice

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Abstract

Purpose

Intervertebral disc degeneration is considered to be a major feature of low back pain. Furthermore, oxidative stress has been shown to be an important factor in degenerative diseases such as osteoarthritis and is considered a cause of intervertebral disc degeneration. The purpose of this study was to clarify the correlation between oxidative stress and intervertebral disc degeneration using Broad complex-Tramtrack-Bric-a-brac and cap‘n’collar homology 1 deficient (Bach 1−/−) mice which highly express heme oxygenase-1 (HO-1). HO-1 protects cells from oxidative stress.

Methods

Caudal discs of 12-week-old and 1-year-old mice were evaluated as age-related models. Each group and period, 5 mice (a total of 20 mice, a total of 20 discs) were evaluated as age-related model. C9–C10 caudal discs in 12-week-old Bach 1−/− and wild-type mice were punctured using a 29-gauge needle as annulus puncture model. Each group and period, 5 mice (a total of 60 mice, a total of 60 discs) were evaluated. The progress of disc degeneration was evaluated at pre-puncture, 1, 2, 4, 8 and 12 weeks post-puncture. Radiographic, histologic and immunohistologic analysis were performed to compare between Bach 1−/− and wild-type mice.

Results

In the age-related model, there were no significant differences between Bach 1−/− and wild-type mice radiologically and histologically. However, in the annulus puncture model, histological scoring revealed significant difference at 8 and 12 weeks post-puncture. The number of HO-1 positive cells was significantly greater in Bach 1−/− mice at every period. The apoptosis rate was significantly lower at 1 and 2 weeks post-puncture in Bach 1−/− mice.

Conclusions

Oxidative stress prevention may avoid the degenerative process of the intervertebral disc after puncture, reducing the number of apoptosis cells. High HO-1 expression may also inhibit oxidative stress and delay the process of intervertebral disc degeneration.

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Acknowledgments

This work was supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology-Japan (No. 20591743). The manuscript submitted does not contain information about medical device(s)/drug(s). Foundation funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan

    Ryo Ohta, Nobuhiro Tanaka, Kazuyoshi Nakanishi, Naosuke Kamei, Toshio Nakamae, Bunichiro Izumi, Yuki Fujioka & Mitsuo Ochi

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  1. Ryo Ohta
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  2. Nobuhiro Tanaka
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  3. Kazuyoshi Nakanishi
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  4. Naosuke Kamei
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  5. Toshio Nakamae
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  6. Bunichiro Izumi
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  7. Yuki Fujioka
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  8. Mitsuo Ochi
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Correspondence to Ryo Ohta.

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Ohta, R., Tanaka, N., Nakanishi, K. et al. Heme oxygenase-1 modulates degeneration of the intervertebral disc after puncture in Bach 1 deficient mice. Eur Spine J 21, 1748–1757 (2012). https://doi.org/10.1007/s00586-012-2442-5

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  • DOI: https://doi.org/10.1007/s00586-012-2442-5

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