Clues for new therapeutics in osteoporosis and periodontal disease: new roles for lipoxygenases?
Lipoxygenase (LOX) pathways are well appreciated for their ability to regulate key events contributing to the cardinal signs of inflammation. Recent evidence indicates that LOX genes are associated with osteoporosis. Also, overexpression of the 15-LOX Type 1 in transgenic rabbits leads to a reduced inflammatory phenotype and protection from periodontal disease, as well as atherosclerosis. Osteoporosis and inflammation-associated bone degradation, such as periodontitis, affect many individuals worldwide and are known to have pathogenesis that involves local mediators via communication between osteoclasts and osteoblasts during osteogenesis. Evidence has emerged indicating that LOX gene expression is associated with reduced bone strength in murine models of osteoporosis. Overexpression of the 15-LOX gene and its products, such as lipoxins, confers endogenous anti-inflammation. This article discusses the recent findings that may link aberrant LOX pathway expression in these diseases, suggesting new avenues for therapeutic approaches via activation of endogenous pathways for resolution of local inflammation.
Serhan
Charles N
CN
Brigham and Women's Hospital and Harvard Medical School, Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, 75 Francis Street, Boston, MA 02115, USA. cnserhan@zeus.bwh.harvard.edu
D000818:Animals; D030801:Animals, Genetically Modified; D001092:Arachidonate 12-Lipoxygenase / Q000502:physiology*; D001093:Arachidonate 15-Lipoxygenase / Q000502:physiology*; D001161:Arteriosclerosis / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D016723:Bone Remodeling / Q000502:physiology; D015777:Eicosanoids / Q000378:metabolism; D004790:Enzyme Induction; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D018836:Inflammation Mediators / Q000378:metabolism; D044045:Lipoxins / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D051379:Mice; D010024:Osteoporosis / Q000188:drug therapy* / Q000201:enzymology; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000201:enzymology; D010518:Periodontitis / Q000188:drug therapy* / Q000201:enzymology; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000502:physiology
C489638:16-(4-fluoro)phenoxylipoxin A4 methyl ester; D015777:Eicosanoids; D018836:Inflammation Mediators; D044045:Lipoxins; D016859:Lipoxygenase Inhibitors; D011993:Recombinant Fusion Proteins; C040527:lipoxin A4; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase