title: Bone substitute materials supplemented with prolyl hydroxylase inhibitors decrease osteoclastogenesis in vitro.
abstract: OBJECTIVE
  Inhibition of prolyl hydroxylases stimulates bone regeneration. Consequently, bone substitute materials were developed that release prolyl hydroxylase inhibitors. However, the impact of prolyl hydroxylase inhibitors released from these carriers on osteoclastogenesis is not clear. We therefore assessed the effect of bone substitute materials that release prolyl hydroxylase inhibitors on osteoclastogenesis.
  
  
  METHODS
  Dimethyloxalylglycine, desferrioxamine, and l-mimosine were lyophilized onto bovine bone mineral and hydroxyapatite, and supernatants were generated. Osteoclastogenesis was induced in murine bone marrow cultures in the presence of the supernatants from bone substitute materials. The formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and TRAP activity were determined. To test for possible effects on osteoclast progenitor cells, we measured the effect of the supernatants on proliferation and viability. In addition, experiments were performed where prolyl hydroxylase inhibitors were directly added to the bone marrow cultures.
  
  
  RESULTS
  We found that prolyl hydroxylase inhibitors released within the first hours from bone substitute materials reduce the number and activity of TRAP-positive multinucleated cells. In line with this, addition of prolyl hydroxylase inhibitors directly to the bone marrow cultures dose-dependently reduced the number of TRAP-positive multinucleated cells and the overall resorption activity. Moreover, the released prolyl hydroxylase inhibitors decreased proliferation but not viability of osteoclast progenitor cells.
  
  
  CONCLUSIONS
  Our results show that prolyl hydroxylase inhibitors released from bone substitute materials decrease osteoclastogenesis in murine bone marrow cultures.
authors.affiliation: Department of Oral Surgery, Medical University of Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Vinzenz
authors.affiliation: Department of Oral Surgery, Medical University of Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schröckmair
authors.affiliation: Department of Oral Surgery, Medical University of Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.|Laboratory of Oral Cell Biology, School of Dental Medicine, University of Bern, Bern, Switzerland.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Gruber
authors.affiliation: Austrian Cluster for Tissue Regeneration, Vienna, Austria.|Department of Conservative Dentistry and Periodontology, Medical University of Vienna, Vienna, Austria.
authors.forename: Hermann
authors.initials: H
authors.lastname: Agis
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D005260:Female; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D064800:Prolyl-Hydroxylase Inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D018786:Bone Substitutes; D064800:Prolyl-Hydroxylase Inhibitors
keywords: bone; bone graft; bone remodeling; cell differentiation; drug delivery/release