Targeting Fas in osteoresorptive disorders

Kovačić, Nataša and Grčević, Danka and Katavić, Vedran and Lukić, Ivan Krešimir and Marušić, Ana (2010) Targeting Fas in osteoresorptive disorders. Expert Opinion on Therapeutic Targets, 14 (10). pp. 1121-1134. ISSN 1472-8222

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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.

Item Type: Article
MeSH: Animals ; Antigens, CD95/antagonists & inhibitors ; Antigens, CD95/metabolism ; Apoptosis ; Bone Resorption/genetics ; Bone Resorption/physiopathology ; Bone and Bones/physiology ; Bone and Bones/physiopathology ; Cell Differentiation ; Cell Lineage ; Fas Ligand Protein/metabolism ; Fas Ligand Protein/pharmacology ; Fas Ligand Protein/therapeutic use ; Gene Expression ; Humans ; Molecular Targeted Therapy ; Osteoblasts/cytology ; Osteoblasts/drug effects ; Osteoblasts/metabolism ; Osteoclasts/cytology ; Osteoclasts/drug effects ; Osteoclasts/metabolism ; Osteogenesis ; Signal Transduction/drug effects
Departments: Katedra za anatomiju i kliničku anatomiju
Katedra za fiziologiju i imunologiju
Depositing User: Marijan Šember
Status: Published
Kovačić, NatašaUNSPECIFIED
Katavić, VedranUNSPECIFIED
Lukić, Ivan KrešimirUNSPECIFIED
Date: October 2010
Date Deposited: 12 Jan 2012 11:19
Last Modified: 12 Jan 2012 11:19
Subjects: /
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