Details

Autor(en) / Beteiligte

• Lin, S.-S.
• Yuan, L.-J.
• Niu, C.-C.
• Tu, Y.-K.
• Yang, C.-Y.
• Ueng, S.W.N.

Titel

Hyperbaric oxygen inhibits the HMGB1/RAGE signaling pathway by upregulating Mir-107 expression in human osteoarthritic chondrocytes

Ist Teil von

• Osteoarthritis and cartilage, 2019-09, Vol.27 (9), p.1372-1381

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• MicroRNA (miRNA)107 expression is downregulated but high mobility group box 1 (HMGB-1), Toll-like receptors (TLRs), and receptor for advanced glycation end products (RAGE) are upregulated in osteoarthritic (OA) cartilage. We investigated mir-107/HMGB-1 signaling in OA after hyperbaric oxygen (HBO) treatment. MiR-107 mimic was transfected and the HMGB-1 was analyzed in OA chondrocytes. MiRNA targets were identified using bioinformatics and a luciferase reporter assay. After HBO treatment, the mRNA or protein levels of HMGB-1, RAGE, TLR2, TLR4, and inducible nitric oxide (NO) synthase (iNOS) and phosphorylation of mitogen-activated protein kinase (MAPK) were evaluated. The secreted HMGB-1 and matrix metalloproteases (MMPs) levels were quantified. Finally, we detected the HMGB-1 and iNOS expression in rabbit cartilage defects. Overexpression of miR-107 suppressed HMGB-1 expression in OA chondrocytes. The 3′UTR of HMGB-1 mRNA contained a ‘seed-matched-sequence’ for miR-107. MiR-107 was induced by HBO and a marked suppression of HMGB-1 was observed simultaneously in OA chondrocytes. Knockdown of miR-107 upregulated HMGB-1 expression in hyperoxic cells. HBO downregulated the mRNA and protein expression of HMGB-1, RAGE, TLR2, TLR4, and iNOS, and the secretion of HMGB-1. HBO decreased the nuclear translocation of nuclear factor (NF)-κB, downregulated the phosphorylation of MAPK, and significantly decreased the secretion of MMPs. Morphological and immunohistochemical observation demonstrated that HBO markedly enhanced cartilage repair and the area stained positive for HMGB-1 and iNOS tended to be lower in the HBO group. HBO inhibits HMGB-1/RAGE signaling related pathways by upregulating miR-107 expression in human OA chondrocytes.