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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine >
Peer-reviewed Journal Articles, etc >
Pentosan polysulfate inhibits IL-1 beta-induced iNOS, c-Jun and HIF-1 alpha upregulation in canine articular chondrocytes
This item is licensed under:Creative Commons Attribution 4.0 International
| Title: | Pentosan polysulfate inhibits IL-1 beta-induced iNOS, c-Jun and HIF-1 alpha upregulation in canine articular chondrocytes |
| Authors: | Bwalya, Eugene C. Browse this author | | Kim, Sangho Browse this author | | Fang, Jing Browse this author | | Wijekoon, H. M. Suranji Browse this author | | Hosoya, Kenji Browse this author | | Okumura, Masahiro Browse this author →KAKEN DB |
| Issue Date: | 4-May-2017 |
| Publisher: | PLOS |
| Journal Title: | PLoS ONE |
| Volume: | 12 |
| Issue: | 5 |
| Start Page: | e0177144 |
| Publisher DOI: | 10.1371/journal.pone.0177144 |
| Abstract: | Osteoarthritic (OA) chondrocytes are shown to express inducible nitric oxide synthase (iNOS) which produces high concentrations of nitric oxide (NO), particularly when stimulated with proinflammatory cytokines. NO is involved in OA cartilage degradation. On the other hand, c-Jun N-terminal Kinase (JNK) pathway mediates the activation and transcription of c-Jun, which is required for interleukin-1 (IL-1)-induction of matrix metalloproteinases-13 (MMP-13) in OA pathogenesis. Therefore, the selective inhibition of iNOS and c-Jun is a promising target for treatment and prevention of OA. The purpose of the study was to investigate the inhibitory effects of pentosan polysulfate (PPS) on IL-1 beta-induced iNOS, c-Jun and HIF-alpha isoforms upregulation in canine articular chondrocytes (CACs). Primary (P0) chondrocytes were isolated and cultured from femoral head cartilages of three (3) dogs. First passage (P1) chondrocytes were preincubated with 0, 1, 5, 15 and 40 mu g/mL of PPS for 4 hr before treatment with 10 ng/mL rhIL-1 beta for a further 8 hr. In addition, we evaluated the effects of single and multiple cytokine with or without LPS on iNOS protein induction. PPS significantly inhibited (P < 0.05) IL-1 beta-induced iNOS, c-Jun and HIF-1 alpha mRNA upregulation in a dose-dependent pattern. iNOS mRNA was significantly inhibited at 15 and 40 mu g/mL whereas c-Jun and HIF-1 alpha were significantly downregulated at 5, 15 and 40 mu g/mL of PPS compared to chondrocytes treated with only rhIL-1 beta. Intriguingly, CACs were recalcitrant to single IL-1 beta, TNF-alpha or LPS-induction of iNOS protein including to a combination of IL-1 beta+TNF-alpha, IL-1 beta+LPS except to TNF-alpha+LPS and IL-1 beta+TNF-alpha+LPS suggestive of a protective mechanism from iNOS detrimental effects on perpetuating OA. IL-1 beta+TNF-alpha+LPS-induced iNOS protein expression was significantly abrogated by PPS. We demonstrate for the first time that PPS is a novel inhibitor of IL-1 beta-induced iNOS, c-Jun, and HIF-1 alpha mRNA upregulation and iNOS protein induction which may be beneficial for prevention and treatment OA. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/68315 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 奥村 正裕
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