Gallium modulates osteoclastic bone resorption in vitro without affecting osteoblasts

• Published in: British journal of pharmacology Vol. 159; no. 8; pp. 1681 - 1692
• Main Authors: Verron, Elise, Masson, Martial, Khoshniat, Solmaz, Duplomb, Laurence, Wittrant, Yohann, Baud'huin, Marc, Badran, Zahi, Bujoli, Bruno, Janvier, Pascal, Scimeca, Jean‐Claude, Bouler, Jean‐Michel, Guicheux, Jérôme
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2010; Nature Publishing Group; Wiley
• Subjects: Acid Phosphatase; Acid Phosphatase - metabolism; Alkaline Phosphatase; Alkaline Phosphatase - metabolism; Animals; Base Sequence; Biochemistry; Biochemistry, Molecular Biology; Bioengineering; Biological and medical sciences; Biomaterials; Bone Resorption; Cancer; Cell Behavior; Cell Differentiation; Cells, Cultured; Cellular Biology; Diseases of the osteoarticular system; DNA Primers; Gallium; Gallium - pharmacology; Genomics; Human health and pathology; Humans; In Vitro Techniques; Isoenzymes; Isoenzymes - metabolism; Life Sciences; Medical sciences; Mice; Molecular biology; osteoblast; Osteoblasts; Osteoblasts - cytology; Osteoblasts - drug effects; osteoclast; osteoporosis; Osteoporosis. Osteomalacia. Paget disease; Pharmacology. Drug treatments; Rabbits; Research Papers; Reverse Transcriptase Polymerase Chain Reaction; Rhumatology and musculoskeletal system; Tartrate-Resistant Acid Phosphatase; Osteoarticular system; Osteoporosis; Gallium; Diseases of the osteoarticular system; bone resorption; Osteoblast; Resorption; Osteoclast; Bone; In vitro
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2010.00665.x

Background and purpose:  Gallium (Ga) has been shown to be effective in the treatment of disorders associated with accelerated bone loss, including cancer‐related hypercalcemia and Paget's disease. These clinical applications suggest that Ga could reduce bone resorption. However, few studies have studied the effects of Ga on osteoclastic resorption. Here, we have explored the effects of Ga on bone cells in vitro. Experimental approach:  In different osteoclastic models [osteoclasts isolated from long bones of neonatal rabbits (RBC), murine RAW 264.7 cells and human CD14‐positive cells], we have performed resorption activity tests, staining for tartrate resistant acid phosphatase (TRAP), real‐time polymerase chain reaction analysis, viability and apoptotic assays. We also evaluated the effect of Ga on osteoblasts in terms of proliferation, viability and activity by using an osteoblastic cell line (MC3T3‐E1) and primary mouse osteoblasts. Key results:  Gallium dose‐dependently (0–100 µM) inhibited the in vitro resorption activity of RBC and induced a significant decrease in the expression level of transcripts coding for osteoclastic markers in RAW 264.7 cells. Ga also dramatically reduced the formation of TRAP‐positive multinucleated cells. Ga down‐regulated in a dose‐dependant manner the expression of the transcription factor NFATc1. However, Ga did not affect the viability or activity of primary and MC3T3‐E1 osteoblasts. Conclusions and implications:  Gallium exhibits a dose‐dependent anti‐osteoclastic effect by reducing in vitro osteoclastic resorption, differentiation and formation without negatively affecting osteoblasts. We provide evidence that this inhibitory mechanism involves down‐regulation of NFATc1 expression, a master regulator of RANK‐induced osteoclastic differentiation.