A Cysteine Protease Inhibitor Prevents Suspension-Induced Declines in Bone Weight and Strength in Rats
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概要
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Abstract In this study, we examined the effects of a potent cysteine protease inhibitor, N-(L-3-trans-carboxyoxirane-2-cabonyl)-L-leucine-4-aminobutylamide (E-64a), on bone weight and strength in tail-suspended rats. We first administered a vehicle or 4 or 8 mg/rat of E-64a to rats fed with a low calcium diet for 7 wks to determine effective doses of E-64a on bone resorption in vivo. Femoral cathepsin K-like activity and serum hydroxyproline level in rats fed with a low calcium diet were significantly higher than those in rats fed with a standard diet. The intraperitoneal injection of 8 mg/rat of E-64a to rats decreased their serum calcium and hydroxyproline concentrations after 3 to 6 hrs in parallel with changes in femoral cathepsin K-like activity, while 4 mg/rat of E-64a had weaker effects on these parameters. Based on these results, we injected 8 mg/rat of E-64a to tail-suspended rats twice a day for 2 wks and compared the results with those of treatment with 1 mg/rat of etidronate, a bisphosphonate, twice a week. In tail-suspended rats, femoral weight and strength, assessed by three-point bending test, significantly decreased from Day 5 to 21,while femoral cathepsin K-like activity and serum calcium and hydroxyproline concentrations did not change. E-64a inhibited femoral cathepsin K-like activity in tail-suspended rats, but etidronate did not. E-64a as well as etidronate significantly prevented the suspension-induced declines in bone weight and strength. However, more frequent injection and higher doses were required for E-64a to exhibit significant efficacy of antiresorption, compared with those of etidronate. Our results suggest that a cysteine protease inhibitor could improve suspension-induced osteopenia by inhibiting cathepsin K-like activity in bone; however, it needs several improvements in the effect as a clinical drug.
- 日本生理人類学会の論文
著者
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Watanabe Chiho
Department of Human Ecology, Graduate School of Medicine, University of Tokyo
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KATUNUMA Nobuhiko
Institute for Health Sciences, Tokushima Bunri University
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Watanabe Chiho
Department Of Environmental Health Sciences Tohoku University School Of Medicine
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Watanabe Chiho
Department Of Nutrition School Of Medicine The University Of Tokushima
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TOWATARI Takae
Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima
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NIKAWA Takeshi
Department of Nutritional Physiology, Institute of Health Biosciences, The University of Tokushima G
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Nikawa T
Dep. Of Nutrition Tokushima Univ. School Of Medicine
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Nikawa Takeshi
Department Of Nutrition School Of Medicine The University Of Tokushima
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Towatari T
Division Of Enzyme Chemistry Institute For Enzyme Research The University Of Tokushima
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Towatari Takae
Division Of Enzyme Chemistry Institute For Enzyme Research
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KISHI Kyoichi
Department of Nutrition, The University of Tokushima School of Medicine
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Kishi Kyoichi
Department Of Nutritional Physiology Institute Of Health Biosciences The University Of Tokushima Gra
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KANO Mihoko
Department of Dental Anesthesiology, Tokyo Dental College
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Ikemoto Madoka
Department of Nutrition, School of Medicine, The University of Tokushima
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Kitano Takako
Department of Nutrition, School of Medicine, The University of Tokushima
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Yoshimoto Makoto
Medical Research Laboratories, Research Center, Taisho Pharmaceutical Co.
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Shizuka Fujiko
Department of Life Science, Nagano Prefectural College
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Kitano Takako
徳島大学医学部
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Kano Mihoko
徳島大学医学部
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Kano Mihoko
Department Of Dental Anesthesiology Tokyo Dental College
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Ikemoto Madoka
Department Of Nutrition School Of Medicine The University Of Tokushima
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Ikemoto Madoka
徳島大学医学部
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Katunuma Nobuhiko
Institute For Health Sciences Tokushima Bunri University
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Yoshimoto Makoto
Medical Research Laboratories Research Center Taisho Pharmaceutical Co.
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Shizuka Fujiko
Department Of Life Science Nagano Prefectural College
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Katunuma Nobuhiko
Institute For Enzyme Research Dept. Of Enzyme Chemistry Tokushima Univ.
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KISHI Kyoichi
Department of Nutrition, School of Medicine, The University of Tokushima
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