The role of caspase activation in the regulation of osteoclast fusion and bone homeostasis
Final Report Abstract
Osteoclasts are multinucleated, bone resorbing cells formed via fusion of monocyte progenitors. Increased osteoclast activity is regularly observed during pathologic states such as rheumatoid arthritis and different forms of osteoporosis. Existing studies identified several genes involved in osteoclast fusion but the basic cellular regulatory mechanisms underlying multinucleation of osteoclasts are poorly understood. Recent experiments proposed a role of phosphatidylserine exposure as well as of caspases in osteoclast development, but these two events have not been linked and the mechanisms underlying the pro-osteoclastic effect of caspases as well as pathways leading to phosphatidylserine exposure in osteoclast precursors are not understood. We hypothesize that osteoclast precursors display a controlled and non- apoptotic caspase activation that results in phosphatidylserine exposure and osteoclast precursor fusion without inducing cell death. To identify novel pathways and targets genes involved in osteoclast fusion will help to design novel therapeutic strategies for the treatment of osteoporosis and bone-related diseases.
Publications
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Metabolic reprogramming of osteoclasts represents a therapeutic target during the treatment of osteoporosis. Scientific Reports, 10(1).
Taubmann, Jule; Krishnacoumar, Brenda; Böhm, Christina; Faas, Maria; Müller, Dorothea I. H.; Adam, Susanne; Stoll, Cornelia; Böttcher, Martin; Mougiakakos, Dimitrios; Sonnewald, Uwe; Hofmann, Jörg; Schett, Georg; Krönke, Gerhard & Scholtysek, Carina
