Pentosan polysulfate inhibits IL-1β-induced iNOS, c-Jun and HIF-1α upregulation in canine articular chondrocytes

Bwalya EC, Kim S, Fang J, Wijekoon HMS, Hosoya K, Okumura M · PLoS One

The anti-inflammatory arm of the mechanism: PPS dose-dependently suppressed interleukin-1β-driven expression of inducible nitric oxide synthase (significant at 15 and 40 µg/mL), c-Jun and HIF-1α (from 5 µg/mL) — the transcriptional route to MMP-13 and nitric-oxide-mediated matrix loss — and abolished iNOS protein induction under combined cytokine and endotoxin stimulation, the only stimulus that induced the protein at all; HIF-2α fell only at 40 µg/mL.

Population

Primary articular chondrocytes from femoral head cartilage of three dogs

Intervention

PPS at 1–40 µg/ml before interleukin-1β stimulation

Comparator

Cytokine-stimulated chondrocytes without PPS

Limitations

Cells from three dogs, two of them juveniles with Legg-Calvé-Perthes disease; messenger-RNA endpoints for most readouts, and concentrations at the upper end of what an injection achieves; the PPS was Cartrophen Vet and the labelled PPS a gift from its developer; no author conflicts declared.