The 12/15-lipoxygenase pathway promotes osteoclast development and differentiation.
Although 12/15-lipoxygenase (12/15-LO) has been implicated as negative regulator of systemic bone mass in mice and humans, the underlying mechanisms remain elusive. Here, we show that 12/15-LO is a positive regulator of osteoclast (OC) development. Enzymatic inhibition as well as genetic ablation of 12/15-LO significantly impaired osteoclastogenesis. Conversely, addition of the 12/15-LO-derived eicosanoids 12- and 15-HETE augmented differentiation of precursors into fully matured OCs. Together these data point towards a crucial role of 12/15-LO in the regulation of OC development. Therefore, 12/15-LO and its human homologue 15-LO may display novel targets for the treatment of diseases such as osteoporosis and rheumatoid arthritis.
Krönke
Gerhard
G
Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054, Erlangen, Germany. gerhard.kroenke@uk-erlangen.de
Uderhardt
Stefan
S
Katzenbeisser
Julia
J
Schett
Georg
G
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology* / Q000201:enzymology*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
D004791:Enzyme Inhibitors; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase