Epigenetic regulation of 15-lipoxygenase-1 expression in human chondrocytes by promoter methylation.

Abstract

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.

• Authors: Sami G Alsabri, Gadid G Guedi, Mehdi Najar, Makram Merimi, Frédéric Lavoie, Detlev Grabs, Julio Fernandes, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Mohamed Benderdour, Hassan Fahmi
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 72 Issue 12 Pg. 2145-2153 (Dec 2023) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 37874359 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Chemical References

• Arachidonate 15-Lipoxygenase
• Scavenger Receptors, Class E
• ALOX15 protein, human

Topics

• Humans
• Arachidonate 15-Lipoxygenase (genetics, metabolism)
• Chondrocytes (metabolism)
• DNA Methylation
• Epigenesis, Genetic
• Osteoarthritis (genetics, metabolism)
• Scavenger Receptors, Class E (genetics, metabolism)