Endothelin‑1 induces oncostatin M expression in osteoarthritis osteoblasts by trans‑activating the oncostatin M gene promoter via Ets‑1
| Autor: | Wanchun Wang, Xin-Zhan Mao, Qi Tang, You Chen, Guoliang Huang, Ren Wu, Lele Liao |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Transcriptional Activation Cancer Research Morpholines Cell Molecular Sequence Data Aminopyridines Oncostatin M Biology Biochemistry Peptides Cyclic Proto-Oncogene Protein c-ets-1 03 medical and health sciences 0302 clinical medicine Piperidines Genes Reporter Osteoarthritis Genetics medicine Humans RNA Messenger RNA Small Interfering Promoter Regions Genetic Molecular Biology PI3K/AKT/mTOR pathway Cells Cultured 030203 arthritis & rheumatology Gene knockdown Binding Sites Osteoblasts Oncogene Base Sequence Endothelin-1 fungi Osteoblast Promoter Molecular biology Endothelin 1 030104 developmental biology medicine.anatomical_structure Oncology biology.protein Molecular Medicine RNA Interference Oligopeptides Protein Binding |
| Zdroj: | Molecular medicine reports. 13(4) |
| ISSN: | 1791-3004 |
| Popis: | Oncostatin M (OSM) contributes to cartilage degeneration in osteoarthritis (OA) and was demonstrated to be expressed in OA osteoblasts. Endothelin‑1 (ET‑1) is implicated in the degradation of OA articular cartilage, and osteoblast proliferation and bone development. In the present study, the effects of ET‑1 on OSM expression in human OA osteoblasts were investigated, to the best of our knowledge, for the first time. Primary human OA osteoblasts were treated with ET‑1 (1, 5, 10, 20 and 30 nM) for 0.5, 1, 2, 3 and 4 h with or without the selective ETA receptor (ETAR) antagonist, BQ123, ETB receptor antagonist, BQ788 or the phosphatidylinositol 3‑kinase (PI3K) inhibitor, BKM120. ET‑1 treatment induced OSM mRNA expression, and the intracellular and secreted protein levels of OA osteoblasts in a dose‑dependent manner. This effect was suppressed by BQ123 and BKM120, but not BQ788 administration. In combination with electrophoretic mobility shift assays, deletional and mutational analyses on the activity of a human OSM promoter/luciferase reporter demonstrated that ET‑1 induced OSM expression in OA osteoblasts by trans‑activating the OSM gene promoter through specific binding of Ets‑1 to an Ets‑1 binding site in the OSM promoter in an ETAR‑ and PI3K‑dependent manner. Furthermore, ET‑1 treatment increased the expression of Ets‑1 in a dose‑dependent manner, however the knockdown of Ets‑1 suppressed the ET1‑induced expression of OSM in OA osteoblasts. In conclusion, the present study demonstrated that ET‑1 induces the expression of OSM in OA osteoblasts by trans‑activating the OSM gene promoter primarily through increasing the expression level of Ets‑1 in an ETAR‑ and PI3K‑dependent manner. The current study suggested novel insights into the mechanistic role of ET‑1 in the pathophysiology of OA. |
| Databáze: | OpenAIRE |
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