title: Gallium modulates osteoclastic bone resorption in vitro without affecting osteoblasts.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  Gallium dose-dependently (0-100 microM) 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
  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.
authors.affiliation: Inserm U, Lioad, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Verron
authors.forename: Martial
authors.initials: M
authors.lastname: Masson
authors.forename: Solmaz
authors.initials: S
authors.lastname: Khoshniat
authors.forename: Laurence
authors.initials: L
authors.lastname: Duplomb
authors.forename: Yohann
authors.initials: Y
authors.lastname: Wittrant
authors.forename: Marc
authors.initials: M
authors.lastname: Baud'huin
authors.forename: Zahi
authors.initials: Z
authors.lastname: Badran
authors.forename: Bruno
authors.initials: B
authors.lastname: Bujoli
authors.forename: Pascal
authors.initials: P
authors.lastname: Janvier
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Scimeca
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bouler
authors.forename: Jérôme
authors.initials: J
authors.lastname: Guicheux
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001862:Bone Resorption; D002454:Cell Differentiation; D002478:Cells, Cultured; D017931:DNA Primers; D005708:Gallium / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D017931:DNA Primers; D007527:Isoenzymes; D005708:Gallium; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase
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