The online version of this article (doi:10.1186/s12891-015-0844-3) contains supplementary material, which is available to authorized users.
The authors declare that none of them has any competing interests.
TS performed and planed the in vitro and in vivo experiments. Further, he performed the data analysis. He wrote the main body of the manuscript. PW and KL synthesized the dPGS used in the study. PW contributed worthful advices and discussions of data. PW and KL revised the manuscript. RH: was an important supervisor of the study. He revised the manuscript. GST: planned and supervised the study. She performed together with TS the in vivo experiments. She contributed parts to the manuscript and thoroughly revised it. She interpreted the data. All authors read and approved the final manuscript.
Tobias Schneider: Department of Orthopaedic, Trauma and Reconstructive Surgery, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany and Institute of Anatomy, Paracelsus Medical University, Salzburg and Nuremberg, Germany, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany
Pia Welker, Kai Licha: IC Discovery GmbH, Robert Koch Platz 4, 10115 Berlin, Germany
Rainer Haag: Institute for Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
Gundula Schulze-Tanzil: Institute of Anatomy, Paracelsus Medical University, Salzburg and Nuremberg, Germany, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany
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.
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.
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.
dPGS presented overall cyto- and biocompatibility, no accumulation in metabolizing organs and chondroprotective properties in the osteoarthritic knee joint.
Additional file 1: Figure S1a1-e2. Characterization of cultured rat primary knee joint chondrocytes. Primary chondrocytes immediately after isolation (passage 0, upper row, a1-e1) and in the first passage (lower row, a2-e2) are depicted light microscopically (a1-2) and were characterized for the expression of type II collagen (green, b1-2), type I collagen (green, c1-2), sox9 (green, d1-2) and vinculin (red)/F-actin (green) (e1-2). Cell nuclei are counterstained using DAPI (blue). a1-2: scale bar 100 μm, b1-e2: scale bar 50 μm. (TIF 7376 kb)12891_2015_844_MOESM1_ESM.tif
Roach H, Tilley S. The Pathogenesis of Osteoarthritis. In: Bronner F, Farach-Carson M, editors. Bone and Osteoarthritis. Topics in Bone Biology: Springer London; United Kingdom: 2007. p. 1–18.
Fernandes JC, Martel-Pelletier J, Pelletier JP. The role of cytokines in osteoarthritis pathophysiology. Biorheology. 2002;39(1–2):237–46. PubMed
Schneider T, Welker P, Haag R, Dernedde J, Hug T, Licha K, et al. Effects of dendritic polyglycerol sulfate onarticular chondrocytes. Inflamm Res. 2015;64(11):917-28.
Iijima H, Aoyama T, Ito A, Tajino J, Nagai M, Zhang X, et al. Destabilization of the medial meniscus leads to subchondral bone defects and site-specific cartilage degeneration in an experimental rat model. Osteoarthritis Cartilage. 2014;22(7):1036–43. doi: 10.1016/j.joca.2014.05.009. CrossRefPubMed
Bove SE, Laemont KD, Brooker RM, Osborn MN, Sanchez BM, Guzman RE, et al. Surgically induced osteoarthritis in the rat results in the development of both osteoarthritis-like joint pain and secondary hyperalgesia. Osteoarthritis Cartilage. 2006;14(10):1041–8. doi: 10.1016/j.joca.2006.05.001. CrossRefPubMed
Wang Y, de Isla N, Huselstein C, Wang B, Netter P, Stoltz JF, et al. Effect of alginate culture and mechanical stimulation on cartilaginous matrix synthesis of rat dedifferentiated chondrocytes. Bio-Med Mater Eng. 2008;18(1 Suppl):S47–54.
Elsaid KA, Zhang L, Waller K, Tofte J, Teeple E, Fleming BC, et al. The impact of forced joint exercise on lubricin biosynthesis from articular cartilage following ACL transection and intra-articular lubricin’s effect in exercised joints following ACL transection. Osteoarthritis Cartilage. 2012;20(8):940–8. doi: 10.1016/j.joca.2012.04.021. CrossRefPubMed
Schleh C, Semmler-Behnke M, Lipka J, Wenk A, Hirn S, Schaffler M, et al. Size and surface charge of gold nanoparticles determine absorption across intestinal barriers and accumulation in secondary target organs after oral administration. Nanotoxicology. 2012;6(1):36–46. doi: 10.3109/17435390.2011.552811. PubMedCentralCrossRefPubMed
- Influence of dendritic polyglycerol sulfates on knee osteoarthritis: an experimental study in the rat osteoarthritis model
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