Objective: Chronic inflammation plays an important role in the osteoarthritis (OA) pathology but how this influence OA disease progression is unclear. Leukotriene B4 (LTB 4 ) is a potent proinflammatory lipid mediator generated from arachidonic acid through the sequential activities of 5-lipoxygenase, 5-lipoxygenase-activating protein, Leukotriene A 4 hydrolase (LTA 4 H) and its downstream product LTB 4 . The aim of this study is to investigate the involvement and the potential therapeutic target of the LTB 4 pathway in OA disease progression.
Design: Both clinical human cartilage samples ( n = 7) and mice experimental OA models ( n = 6) were used. The levels of LTA 4 H and leukotriene B4 receptor 1 were first examined using immunostaining in human OA/non-OA cartilage and mice experimental OA models. We also determined whether the LTA 4 H pathway was associated with cartilage degeneration and synovitis inflammation in OA mice models and human articular chondrocytes.
Results: We found that both LTA 4 H and LTB 4 receptor (BLT1) were highly expressed in human and mice OA cartilage. Inhibition of LTA 4 H suppressed cartilage degeneration and synovitis in OA mice model. Furthermore, inhibition of LTA 4 H promoted cartilage regeneration by upregulating chondrogenic genes expression such as aggrecan ( ACAN ), collagen 2A1 ( COL2A1 ), and SRY-Box transcription factor 9 ( SOX9 ).
Conclusions: Our results indicate that the LTA 4 H pathway is a crucial regulator of OA pathogenesis and suggest that LTA 4 H could be a therapeutic target in combat OA.
Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.