title: A phosphorus-based dendrimer targets inflammation and osteoclastogenesis in experimental arthritis.
abstract: Dendrimers are highly branched "tree-like" polymers that have demonstrated therapeutic potential in drug delivery, medical imaging, and tissue engineering in recent years. In addition, we have shown that an azabisphosphonate (ABP)-capped dendrimer selectively targets monocytes and directs them toward anti-inflammatory activation. We explored this property to assess the therapeutic potential of dendrimer ABP in the treatment of an inflammatory disease, rheumatoid arthritis. Intravenous injections of dendrimer ABP inhibited the development of inflammatory arthritis in two animal models: IL-1ra(-/-) mice and mice undergoing K/BxN serum transfer. Suppression of disease was characterized by normal synovial membranes, reduced levels of inflammatory cytokines, and the absence of cartilage destruction and bone erosion. Dendrimer ABP also exhibited anti-osteoclastic activity on mouse and human cells, mediated by c-FMS (cellular-feline McDonough strain sarcoma virus oncogene homolog) inhibition. These preclinical demonstrations suggest the potential use of dendrimer ABP as a nanotherapeutic for rheumatoid arthritis.
authors.affiliation: INSERM, U1043, Toulouse F-31300, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Hayder
authors.forename: Mary
authors.initials: M
authors.lastname: Poupot
authors.forename: Michel
authors.initials: M
authors.lastname: Baron
authors.forename: Delphine
authors.initials: D
authors.lastname: Nigon
authors.forename: Cédric-Olivier
authors.initials: CO
authors.lastname: Turrin
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Caminade
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Majoral
authors.forename: Robert A
authors.initials: RA
authors.lastname: Eisenberg
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
authors.forename: Alain
authors.initials: A
authors.lastname: Cantagrel
authors.forename: Rémy
authors.initials: R
authors.lastname: Poupot
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Davignon
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D015153:Blotting, Western; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry*; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D010758:Phosphorus / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050071:Bone Density Conservation Agents; D050091:Dendrimers; D004164:Diphosphonates; D004337:Drug Carriers; D010758:Phosphorus