Epigenetic regulation of 15-lipoxygenase-1 expression in human chondrocytes by promoter methylation
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG..
OBJECTIVE AND DESIGN: 15-Lipoxygenase-1 (15-LOX-1) catalyzes the biosynthesis of many anti-inflammatory and immunomodulatory lipid mediators and was reported to have protective properties in several inflammatory conditions, including osteoarthritis (OA). This study was designed to evaluate the expression of 15-LOX-1 in cartilage from normal donors and patients with OA, and to determine whether it is regulated by DNA methylation.
METHODS: Cartilage samples were obtained at autopsy from normal knee joints and from OA-affected joints at the time of total knee joint replacement surgery. The expression of 15-LOX-1 was evaluated using real-time polymerase chain reaction (PCR). The role of DNA methylation in 15-LOX-1 expression was assessed using the DNA methyltransferase inhibitor 5-Aza-2'-desoxycytidine (5-Aza-dC). The effect of CpG methylation on 15-LOX-1 promoter activity was evaluated using a CpG-free luciferase vector. The DNA methylation status of the 15-LOX-1 promoter was determined by pyrosequencing.
RESULTS: Expression of 15-LOX-1 was upregulated in OA compared to normal cartilage. Treatment with 5-Aza-dC increased 15-LOX-1 mRNA levels in chondrocytes, and in vitro methylation decreased 15-LOX-1 promoter activity. There was no difference in the methylation status of the 15-LOX-1 gene promoter between normal and OA cartilage.
CONCLUSION: The expression level of 15-LOX-1 was elevated in OA cartilage, which may be part of a repair process. The upregulation of 15-LOX-1 in OA cartilage was not associated with the methylation status of its promoter, suggesting that other mechanisms are involved in its upregulation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:72 |
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| Enthalten in: |
Inflammation research : official journal of the European Histamine Research Society ... [et al. - 72(2023), 12 vom: 24. Dez., Seite 2145-2153 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Alsabri, Sami G [VerfasserIn] |
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| Links: |
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| Themen: |
15-LOX-1 |
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| Anmerkungen: |
Date Completed 29.11.2023 Date Revised 29.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00011-023-01805-0 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363666400 |
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| 245 | 1 | 0 | |a Epigenetic regulation of 15-lipoxygenase-1 expression in human chondrocytes by promoter methylation |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG. | ||
| 520 | |a OBJECTIVE AND DESIGN: 15-Lipoxygenase-1 (15-LOX-1) catalyzes the biosynthesis of many anti-inflammatory and immunomodulatory lipid mediators and was reported to have protective properties in several inflammatory conditions, including osteoarthritis (OA). This study was designed to evaluate the expression of 15-LOX-1 in cartilage from normal donors and patients with OA, and to determine whether it is regulated by DNA methylation | ||
| 520 | |a METHODS: Cartilage samples were obtained at autopsy from normal knee joints and from OA-affected joints at the time of total knee joint replacement surgery. The expression of 15-LOX-1 was evaluated using real-time polymerase chain reaction (PCR). The role of DNA methylation in 15-LOX-1 expression was assessed using the DNA methyltransferase inhibitor 5-Aza-2'-desoxycytidine (5-Aza-dC). The effect of CpG methylation on 15-LOX-1 promoter activity was evaluated using a CpG-free luciferase vector. The DNA methylation status of the 15-LOX-1 promoter was determined by pyrosequencing | ||
| 520 | |a RESULTS: Expression of 15-LOX-1 was upregulated in OA compared to normal cartilage. Treatment with 5-Aza-dC increased 15-LOX-1 mRNA levels in chondrocytes, and in vitro methylation decreased 15-LOX-1 promoter activity. There was no difference in the methylation status of the 15-LOX-1 gene promoter between normal and OA cartilage | ||
| 520 | |a CONCLUSION: The expression level of 15-LOX-1 was elevated in OA cartilage, which may be part of a repair process. The upregulation of 15-LOX-1 in OA cartilage was not associated with the methylation status of its promoter, suggesting that other mechanisms are involved in its upregulation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 15-LOX-1 | |
| 650 | 4 | |a Cartilage | |
| 650 | 4 | |a DNA methylation | |
| 650 | 4 | |a Epigenetics | |
| 650 | 4 | |a Osteoarthritis chondrocyte | |
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| 700 | 1 | |a Najar, Mehdi |e verfasserin |4 aut | |
| 700 | 1 | |a Merimi, Makram |e verfasserin |4 aut | |
| 700 | 1 | |a Lavoie, Frédéric |e verfasserin |4 aut | |
| 700 | 1 | |a Grabs, Detlev |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandes, Julio |e verfasserin |4 aut | |
| 700 | 1 | |a Pelletier, Jean-Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Martel-Pelletier, Johanne |e verfasserin |4 aut | |
| 700 | 1 | |a Benderdour, Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a Fahmi, Hassan |e verfasserin |4 aut | |
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