Inhibition of Leukotriene A Hydrolase Suppressed Cartilage Degradation and Synovial Inflammation in a Mouse Model of Experimental Osteoarthritis.

OBJECTIVE

Chronic inflammation plays an important role in the osteoarthritis (OA) pathology but how this influence OA disease progression is unclear. Leukotriene B4 (LTB) is a potent proinflammatory lipid mediator generated from arachidonic acid through the sequential activities of 5-lipoxygenase, 5-lipoxygenase-activating protein, Leukotriene A hydrolase (LTAH) and its downstream product LTB. The aim of this study is to investigate the involvement and the potential therapeutic target of the LTB pathway in OA disease progression.

DESIGN

Both clinical human cartilage samples ( = 7) and mice experimental OA models ( = 6) were used. The levels of LTAH 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 LTAH pathway was associated with cartilage degeneration and synovitis inflammation in OA mice models and human articular chondrocytes.

RESULTS

We found that both LTAH and LTB receptor (BLT1) were highly expressed in human and mice OA cartilage. Inhibition of LTAH suppressed cartilage degeneration and synovitis in OA mice model. Furthermore, inhibition of LTAH promoted cartilage regeneration by upregulating chondrogenic genes expression such as aggrecan (), collagen 2A1 (), and SRY-Box transcription factor 9 ().

CONCLUSIONS

Our results indicate that the LTAH pathway is a crucial regulator of OA pathogenesis and suggest that LTAH could be a therapeutic target in combat OA.