This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nishimura, F. Articles by Murayama, Y. Search for Related Content PubMed PubMed Citation Articles by Nishimura, F. Articles by Murayama, Y.

(American Journal of Pathology. 2002;161:2047-2052.)
© 2002 American Society for Investigative Pathology

Regular Articles

Cathepsin-L, a Key Molecule in the Pathogenesis of Drug-Induced and I-Cell Disease-Mediated Gingival Overgrowth

A Study with Cathepsin-L-Deficient Mice

Fusanori Nishimura^*, Hisa Naruishi^*, Koji Naruishi^*, Teruo Yamada, Junzo Sasaki, Christoph Peters, Yasuo Uchiyama and Yoji Murayama^*

From the Department of Pathophysiology/Periodontal Science,^* and the Department of Cytology and Histology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan; the Department of Cell Biology and Neuroscience, Osaka University Graduate School of Medicine, Osaka, Japan; and the Institut für Molekulare Medizin und Zellforschung, Albert Ludwigs Universität Freiburg, Freiburg, Germany

Drug-induced gingival overgrowth, the chronic side effect of calcium antagonists, is frequently seen due to the increase in patients with hypertension, although the etiology of the disease is largely unknown. I-cell disease, which accompanies gingival overgrowth, is characterized by a deficiency in UDP-N-acetyl-glucosamine and is classified as one of the lysosomal storage diseases. Here, we hypothesized that a common mechanism may underlie the etiology of gingival overgrowth seen in patients treated with calcium antagonist and in patients with I-cell disease. A calcium antagonist, nifedipine, specifically suppressed cathepsin-L activity and mRNA expression, but not that of cathepsin-B in cultured gingival fibroblasts. The activity of cathepsin-L was suppressed up to 50% at 24 hours after treatment of the cells with the reagent. The selective suppression of cathepsin-L activity appeared not to be dependent on Ca²⁺, since treatment of the cells with thapsigargin suppressed both cathepsin-B and -L activity. Mice deficient in the cathepsin-L gene manifested enlarged gingivae. Histological observation of the gingivae demonstrated typical features of acanthosis, a phenotype very similar to that of experimentally induced gingival overgrowth. Since cathepsin-L deficiency was reported to be associated with thickening of the skin, impaired cathepsin-L activity may play a key role in the establishment of skin and gingival abnormalities seen in I-cell disease. In addition, reduced cathepsin-L activity may play an important role in inducing drug-induced gingival overgrowth.

This article has been cited by other articles:

				P. Bullon, I. Gallardo, G. Goteri, C. Rubini, M. Battino, J. Ribas, and H.N. Newman Nifedipine and Cyclosporin Affect Fibroblast Calcium and Gingiva J. Dent. Res., April 1, 2007; 86(4): 357 - 362. [Abstract] [Full Text] [PDF]

				T. Reinheckel, S. Hagemann, S. Dollwet-Mack, E. Martinez, T. Lohmuller, G. Zlatkovic, D. J. Tobin, N. Maas-Szabowski, and C. Peters The lysosomal cysteine protease cathepsin L regulates keratinocyte proliferation by control of growth factor recycling J. Cell Sci., August 1, 2005; 118(15): 3387 - 3395. [Abstract] [Full Text] [PDF]

				P. C. Trackman and A. Kantarci CONNECTIVE TISSUE METABOLISM AND GINGIVAL OVERGROWTH Crit. Rev. Oral. Biol. Med., May 1, 2004; 15(3): 165 - 175. [Abstract] [Full Text] [PDF]