title: Dual effect of inorganic polymeric phosphate/polyphosphate on osteoblasts and osteoclasts in vitro.
abstract: Inorganic polymeric phosphate/polyphosphate (polyP) is a natural polymer existing in both pro- and eukaryotic systems. In the present study the effect of polyP as well as of polyP supplied in a stoichiometric ratio of 2 m polyP:1 m CaCl2 [polyP (Ca(2+) complex)] on the osteoblast-like SaOS-2 cells and the osteoclast-like RAW 264.7 cells was determined. Both polymers are non-toxic for these cells up to a concentration of 100 µm. In contrast to polyP, polyP (Ca(2+) complex) significantly induced hydroxyapatite formation at a concentration > 10 µm, as documented by alizarin red S staining and scanning electron microscopic (SEM) inspection. Furthermore, polyP (Ca(2+) complex) triggered in SaOS-2 cells transcription of BMP2 (bone morphogenetic protein 2), a cytokine involved in maturation of hydroxyapatite-forming cells. An additional activity of polyP (Ca(2+) complex) is described by showing that this polymer impairs osteoclastogenesis. At concentrations > 10 µm polyP (Ca(2+) complex) slows down the progression of RAW 264.7 cells to functional osteoclasts, as measured by the expression of TRAP (tartrate-resistant acid phosphatase). Finally, it is shown that 10-100 µm polyP (Ca(2+) complex) inhibited phosphorylation of IκBα by the respective kinase in RAW 264.7 cells. We concluded that polyP (Ca(2+) complex) displays a dual effect on bone metabolizing cells. It promotes hydroxyapatite formation in SaOS-2 cells (osteoblasts) and impairs maturation of the osteoclast-related RAW 264.7 cells.
authors.affiliation: National Research Centre for Geoanalysis, Chinese Academy of Geological Sciences, Beijing, People's Republic of China; ERC Advanced Investigator Grant Research Group, Institute for Physiological Chemistry, University Medical Centre, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Heinz C
authors.initials: HC
authors.lastname: Schröder
authors.forename: Bärbel
authors.initials: B
authors.lastname: Diehl-Seifert
authors.forename: Klaus
authors.initials: K
authors.lastname: Kropf
authors.forename: Ute
authors.initials: U
authors.lastname: Schlossmacher
authors.forename: Matthias
authors.initials: M
authors.lastname: Wiens
authors.forename: Werner E G
authors.initials: WE
authors.lastname: Müller
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017886:Durapatite / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011108:Polymers / Q000494:pharmacology*; D011122:Polyphosphates / Q000494:pharmacology*; D053245:RANK Ligand / Q000494:pharmacology; D013194:Staining and Labeling
chemical_list: D000880:Anthraquinones; D055396:Bone Morphogenetic Protein 2; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D011108:Polymers; D011122:Polyphosphates; D053245:RANK Ligand; D000072000:NF-KappaB Inhibitor alpha; C010078:alizarin; D017886:Durapatite