The Multifarious Functions of Leukotrienes in Bone Metabolism

Bone profile of 5-LO –deficient mouse model. We investigated the effects of leukotrienes on bone metabolism using a 5-LO KO mouse model. Long bones phenotype of females and males lacking 5-LO present thicker cortical bone and increased marrow area but decreased trabecular bone only in females. Osteoblasts from 5-LO KO mice show overexpression of bone formation markers leading to a decreased proliferation and increased osteoblast differentiation and mineralization. The osteoclastogenic profile of 5-LO KO mice presents impaired osteoclasts with the downregulation of bone resorption markers and cytokines, leading t o a dysfunctional cell, and impaired resorptive function. The increased bone formation and reduced bone resorption lead to an increased bone turnover, demonstrating that the absence of 5-LO is related to the greater osteogenic profile. ABSTRACTLeukotrienes (LTs) are derived from arachidonic acid metabolism by the 5-lipoxygenase (5-LO) enzyme. The production of LTs is stimulated in the pathogenesis of rheumatoid arthritis (RA), osteoarthritis, and periodontitis, with a relevant contribution to bone resorption. However, its role in bone turnover, particularly the suppression of bone formation by modulating the function of osteoclasts and osteoblasts, remains unclear. We investigated the effects of LTs on bone metabolism and their impact on osteogenic differentiation and osteoclastogenesis using a 5-LO knockout (KO) mouse model. Results from micro-computed tomography (...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Research Article Source Type: research