Targeting Fas in osteoresorptive disorders.

IMPORTANCE OF THE FIELD 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. AREAS COVERED IN THIS REVIEW 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. WHAT THE READER WILL GAIN 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. TAKE HOME MESSAGE 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.