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Gene Expression Changes in an Early Stage of Intervertebral Disc Degeneration Induced by Passive Cigarette Smoking

Uei, Hiroshi, MD*†; Matsuzaki, Hiromi, MD*; Oda, Hiroshi, MD*; Nakajima, Shinya, MD*†; Tokuhashi, Yasuaki, MD*; Esumi, Mariko, PhD


In the March 2006 issue of Spine in the article by Uei et al, “Gene expression changes in an early stage of intervertebral disc degeneration induced by passive cigarette smoking”, some data had been previously published in “Uei H, Matsuzaki H, Esumi M. Ratto Kitsuen Moderu ni okoru Tsuikanban Hensei to Idenshi Hatsugen Henka no Kaiseki.” “Alternations of Gene expression Associated with Histological Changes of Intervertebral Discs in Smoking Rats” (in Japanese) in The Nihon University Journal of Medicine in Volume 61, 2002.

Spine. 44(10):E632, May 15, 2019.

doi: 10.1097/
Basic Science

Study Design. This study attempts to determine the molecular changes in intervertebral disc degeneration of rats induced by passive cigarette smoking.

Objectives. To quantitate and compare the gene expression levels in intervertebral discs from passively cigarette smoking rats and nonsmoking rats.

Summary of Background Data. The molecular mechanism of intervertebral disc degeneration has been investigated mainly in vitro but little in vivo, and gene expression analysis has been performed in a few studies. The cigarette smoking is a risk factor of low back pain. We developed a smoking box to create a rat model of intervertebral disc degeneration induced by passive cigarette smoking.

Methods. Total RNA was extracted from intervertebral discs of rats that were raised in a cigarette-smoking box for 2 to 7 weeks. After synthesis of cDNA, the quantitative analysis of gene expression was performed by the real-time PCR. The remaining spines were subjected to the histologic examination.

Results. Histologic changes of the nucleus pulposus and the anulus fibrosus were detected after 2 weeks of smoking and were frequently found after 7 weeks. Collagen genes were downregulated remarkably after 7 weeks of smoking. No significant increase was observed in the expressions of matrix metalloproteinase-3, but the expression of tissue inhibitor of metalloproteinases-1 started to increase at 4 weeks of smoking. Aggrecan also started to be up-regulated at 4 weeks.

Conclusions. Changes in gene expression by passive cigarette smoking precede the histologic changes in the intervertebral discs. Reactions to suppress the destruction of tissue matrix and to regenerate the intervertebral discs are occurring at the same time as the degenerative histologic changes.

The quantitative analysis of gene expression in the rat intervertebral disc tissue demonstrates that the effect of passive cigarette smoking decreases the expression of major genes at an early period, but when histologic changes related with degeneration appear, reactions to suppress tissue matrix destruction and to heal the intervertebral discs are occurring.

From the Departments of *Orthopaedic Surgery and †Pathology, Nihon University School of Medicine, Tokyo, Japan.

Acknowledgment date: August 5, 2004. First revision date: February 21, 2005. Acceptance date: March 4, 2005.

The manuscript submitted does not contain information about medical device(s)/drug(s).

No 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.

Address correspondence and reprint requests to Mariko Esumi, PhD, Department of Pathology, Nihon University School of Medicine, 30-1, Ooyaguchikami-machi, Itabashi-ku, Tokyo 173-8610, Japan. E-mail:

© 2006 Lippincott Williams & Wilkins, Inc.