Effects of dendritic polyglycerol sulfate on articular chondrocytes.
BACKGROUND
Inflammatory processes driven by cytokines play a crucial role during osteoarthritis (OA) progression. Dendritic polyglycerol sulfate (dPGS) was analyzed in vitro for its effects on articular chondrocytes, cartilage and cytokines involved in the OA process.


METHODS
The metabolic activity of cultured human articular chondrocytes stimulated for 24 h with dPGS (10(-3)-10(-6) mol/L) was monitored using AlamarBlue(®) assay. The dPGS uptake was studied using fluorescence labeled nanoparticles. Further, chondrocytes were either treated with 10(-6) M dPGS, TNFα (10 ng/mL) alone or with a combination of both. The influence on extracellular matrix components, pro- and anti-inflammatory cytokines, matrix metalloproteinase (MMP)1 and the anaphylatoxin receptor C3aR was analyzed by RTD-PCR, flow cytometry and ELISA.


RESULTS
Even at higher dosages (10(-3) mol/L), dPGS did not influence chondrocytes viability. Uptake of dPGS was successfully monitored in human articular chondrocytes and synovial fibroblasts, penetration into cartilage chips was up to ~50 µm. Cellular treatment with dPGS had no effect on synthesis of pro-inflammatory cytokines TNFα and IL-6, but expression of the anti-inflammatory IL-10 was upregulated. Cotreatment with TNFα and dPGS reduced the TNFα level, while IL-1β, IL-6 and IL-10 expression did not change. Collagen type II gene expression was significantly reduced after preincubating cells with dPGS, but remained unaffected at the protein level.


CONCLUSIONS
Results indicate that dPGS could play a role in regulation of cytokines associated with the inflammatory aspect of OA progression.
Department of Orthopedic, Trauma and Reconstructive Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Garystrasse 5, 14195, Berlin, Germany.
Tobias
T
Schneider
Mivenion GmbH, Robert Koch Platz 4, 10115, Berlin, Germany.
Pia
P
Welker
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, 14195, Berlin, Germany.
Rainer
R
Haag
Department of Laboratory Medicine and Clinical Chemistry, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
Jens
J
Dernedde
Department of Laboratory Medicine and Clinical Chemistry, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
Thomas
T
Hug
Mivenion GmbH, Robert Koch Platz 4, 10115, Berlin, Germany.
Kai
K
Licha
Department of Orthopedic, Trauma and Reconstructive Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Garystrasse 5, 14195, Berlin, Germany.
Benjamin
B
Kohl
Department of Orthopedic, Trauma and Reconstructive Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Garystrasse 5, 14195, Berlin, Germany.
Stephan
S
Arens
Department of Orthopedic, Trauma and Reconstructive Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Garystrasse 5, 14195, Berlin, Germany.
Wolfgang
W
Ertel
Department of Orthopedic, Trauma and Reconstructive Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Garystrasse 5, 14195, Berlin, Germany. gundula.schulze@pmu.ac.at.|Institute of Anatomy, Paracelsus Medical University, Salzburg and Nuremberg, General Hospital Nuremberg, Prof.-Ernst-Nathan-Strasse 1, 90419, Nuremberg, Germany. gundula.schulze@pmu.ac.at.
Gundula
G
Schulze-Tanzil
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology; D002460:Cell Line; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D050091:Dendrimers / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005990:Glycerol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011108:Polymers / Q000494:pharmacology*; D013552:Swine
D024043:Collagen Type II; D016207:Cytokines; D050091:Dendrimers; D011108:Polymers; C043941:polyglycerol; D005990:Glycerol
Chondrocytes; Cytokines; Nanoparticles; Synovial fibroblasts