title: Influence of dendritic polyglycerol sulfates on knee osteoarthritis: an experimental study in the rat osteoarthritis model.
abstract: BACKGROUND
  Anti-inflammatory nanoparticular compounds could represent a strategy to diminish osteoarthritis (OA) progression. The present study was undertaken to prove the uptake of nanoparticular dendritic polyglycerol sulfates (dPGS) by rat-derived articular chondrocytes and to answer the question of whether dPGS could modulate knee joint cartilage degradation in a rat OA model and whether complications could arise.
  
  
  METHODS
  dPGS uptake and cytotoxicity was assessed in cultured primary rat-derived articular chondrocytes. Subsequently, OA was induced in the right knee joints of 12 male Wistar rats by medial collateral ligament and meniscus transection. Unoperated left knees remained as controls. Six weeks post surgery six rats were either treated daily (14 days) with 30 mg/kg dPGS (s.c.) or a similar volume of physiological saline. Animals were analyzed clinically for gait alterations. Explanted knee joints were studied histologically using OA scores according to Mankin (1971), Glasson et al., (2010) and the synovitis score according to Krenn et al., (2006). Liver, spleen and kidneys were analyzed for degenerative changes due to dPGS accumulation.
  
  
  RESULTS
  dPGS was taken up after 2 hours by the chondrocytes. Whereas no significant clinical signs of OA could be detected, at the histological level, all operated rat knee joints revealed features of OA in the medial compartment. The values produced by both OA score systems were lower in rats treated with dPGS compared with saline-treated animals. Synovitis score did not significantly differ between the groups. The analyzed organs revealed no degenerative changes.
  
  
  CONCLUSIONS
  dPGS presented overall cyto- and biocompatibility, no accumulation in metabolizing organs and chondroprotective properties in the osteoarthritic knee joint.
authors.affiliation: Department of Orthopaedic, Trauma and Reconstructive Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. tobias.schneider@charite.de.|Institute of Anatomy, Paracelsus Medical University, Salzburg and Nuremberg, Germany, Prof. Ernst Nathan Str. 1, Nuremberg, 90419, Germany. tobias.schneider@charite.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schneider
authors.affiliation: IC Discovery GmbH, Robert Koch Platz 4, Berlin, 10115, Germany. welker@mivenion.com.
authors.forename: Pia
authors.initials: P
authors.lastname: Welker
authors.affiliation: IC Discovery GmbH, Robert Koch Platz 4, Berlin, 10115, Germany. licha@ic-discovery.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Licha
authors.affiliation: Institute for Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany. rainer.haag@gmx.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
authors.affiliation: Department of Orthopaedic, Trauma and Reconstructive Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. gundula.schulze@pmu.ac.at.|Institute of Anatomy, Paracelsus Medical University, Salzburg and Nuremberg, Germany, Prof. Ernst Nathan Str. 1, Nuremberg, 90419, Germany. gundula.schulze@pmu.ac.at.
authors.forename: Gundula
authors.initials: G
authors.lastname: Schulze-Tanzil
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D050091:Dendrimers / Q000008:administration & dosage / Q000378:metabolism*; D004195:Disease Models, Animal; D005990:Glycerol / Q000008:administration & dosage / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011108:Polymers / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D050091:Dendrimers; D011108:Polymers; D013431:Sulfates; C043941:polyglycerol; D005990:Glycerol