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Gallium inhibits bone resorption by a direct effect on osteoclasts
Affiliation:1. Merrell Dow Research Institute, 16 Rue d''Ankara, 67084 Strasbourg Cedex France;2. Department of Histopathology, St. George''s Hospital Medical School, London SW17 ORE, England;1. Department of Cardiology, University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany;2. DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg, Germany;1. Divison of Connective Tissue Disease (Rheumatology), Department of Medicine, The University of Tennessee Health Science Center, 956 Court Avenue, Suite G326, Memphis, TN, 38163-0001, USA;2. Section of Immunology, Allergy and Rheumatology, Department of Medicine, Biology of Inflammation Center, Baylor College of Medicine, Houston, TX, USA;1. University of Liège – Gembloux Agro Bio Tech, Unit Analyzes, Quality, Risks, Laboratory of Analytical Chemistry, Passage des Déportés, 2, B-5030 Gembloux, Belgium;2. Kashin–Beck Disease Fund asbl-vzw, Rue de l’Aunee, 6, B-6953 Forrieres, Belgium;3. Department and Laboratory of Pediatric, Free Universities of Brussels, Brussels, Belgium;1. Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Osaka, Japan;2. Department of Medical Technology, Faculty of Health Sciences, Kansai University of Health Sciences, Osaka, Japan;3. Health Care Center, Osaka University, Osaka, Japan
Abstract:Gallium nitrate has been used clinically to treat cancer-related hypercalcemia. It has been suggested that gallium may reduce calcium release from bone by inhibiting bone resorption, but the mechanism(s) involved remain to be elucidated. Therefore, we have examined the effect of gallium on bone resorption in vitro using osteoclasts isolated from neonatal rat long bones cultured on slices of cortical bone. Gallium nitrate (0.01–100 μg/ml) produced a concentration-dependent inhibition of bone resorption. Morphological studies showed that even (100μg/ml) gallium nitrate induced no light microscopical change in osteoclast morphology and did not affect their survival on bone slices. Pretreatment of bone slices with gallium nitrate (100μg/ml for 18 h), followed by extensive washing also inhibited subsequent osteoclastic bone resorption. These results suggest that gallium can be adsorbed onto the calcified surface of bone and inhibit osteoclastic bone resorption.
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