Targeting Fas in osteoresorptive disorders.
BACKGROUND
Fas receptor is a mediator of the external apoptotic pathway in many cells and tissues. It is proposed that Fas receptor mediates osteoresorptive effects of estrogen deficiency and local/systemic inflammation.


METHODS
This review covers the past two decades of research on the expression and function of the Fas-Fas ligand system on bone cells, involvement in the pathogenesis of osteoresorption and potential therapeutic modulation.


RESULTS
We review the structure, biological function and intracellular signaling pathways of the Fas-Fas ligand system emphasizing the role of the non-apoptotic signaling pathways in bone cells, particularly osteoblast differentiation. We also present data on the in vitro expression and function of the Fas-Fas ligand system on osteoblast/osteoclast lineage cells, animal and human studies confirming its involvement in osteoresorptive disorders and potential therapeutic approaches to modulate its function.


CONCLUSIONS
Tissue specific therapeutic approaches need to be established to modify the Fas-Fas ligand system in osteoresorptive disorders as systemic targeting has many side effects. The most promising approach would be to target Fas signaling molecules coupled with osteoblast/osteoclast differentiation pathways, but a precise definition of these targets is still needed.
Kovacic
Natasa
N
University of Zagreb School of Medicine, Department of Anatomy, Zagreb, HR-10000, Croatia. natasa@mef.hr
Grcevic
Danka
D
Katavic
Vedran
V
Lukic
Ivan Kresimir
IK
Marusic
Ana
A
D000818:Animals; D017209:Apoptosis; D001862:Bone Resorption / Q000235:genetics / Q000503:physiopathology*; D001842:Bone and Bones / Q000502:physiology / Q000503:physiopathology; D002454:Cell Differentiation; D019070:Cell Lineage; D053222:Fas Ligand Protein / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D015870:Gene Expression; D006801:Humans; D058990:Molecular Targeted Therapy; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis; D015398:Signal Transduction / Q000187:drug effects; D019014:fas Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism
D053222:Fas Ligand Protein; D019014:fas Receptor