title: Osteoclast apoptosis: the role of Fas in vivo and in vitro.
abstract: Both the number and the activity of osteoclasts are critical for maintaining normal bone turnover. The number is determined by rates of cell differentiation and death. Fas-mediated apoptosis is a dominant mechanism for apoptosis. Here, we show the presence of the Fas receptor on mouse, human, avian, and cultured RAW264.7 (murine) derived osteoclasts and the up-regulation of its expression during mouse osteoclast differentiation. Additionally, Fas is a fully functional death receptor in osteoclasts, and its signaling pathway is consistent with classical Fas signaling in other cell systems, involving mitochondrial release of cytochrome c and activation of caspases 3 and 9. This demonstration of Fas-mediated apoptosis in mature osteoclasts provides a new and potent mechanism for the regulation of osteoclast life span. The in vivo significance of Fas-mediated apoptosis in bone (osteoclasts) was demonstrated in aged Lpr and Gld mice, which have a dysfunctional immune system. Lpr mice, which have a defect in the Fas gene, have decreased bone mineral density, bone volume, trabecular thickness, and increased osteoclast number. Gld mice, which have a Fas ligand mutation, have a slight yet insignificant decrease in bone mineral density, but a highly significant increase in osteoclast number. Taken together, these data demonstrate that the Fas/Fas ligand system is important in the regulation of bone turnover and may represent a critical link between the immune system and bone remodeling in development and in various diseases.
authors.affiliation: Department of Pathology, Nutrition Sciences, University of Alabama at Birmingham, Alabama 35294-0007, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wu
authors.forename: Margaret A
authors.initials: MA
authors.lastname: McKenna
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.forename: Tim R
authors.initials: TR
authors.lastname: Nagy
authors.forename: Jay M
authors.initials: JM
authors.lastname: McDonald
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015519:Bone Density; D016723:Bone Remodeling / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000276:immunology; D002645:Chickens; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000502:physiology; D066298:In Vitro Techniques; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009000:Monocytes / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology*; D015398:Signal Transduction / Q000502:physiology; D019014:fas Receptor / Q000502:physiology*
chemical_list: D019014:fas Receptor