Targeting Fas in osteoresorptive disorders

Scientific paper - Original scientific paper

• Author: Nataša Kovačić
• Author: Danka Grčević
• Author: Vedran Katavić
• Author: Ivan Krešimir Lukić
• Author: Ana Marušić
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences

Abstract (english)

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.

• Keywords (english): 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
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Accepted version
• Journal title: Expert Opinion on Therapeutic Targets
• Numbering: vol. 14, no. 10, pp. 1121-1134
• p-ISSN: 1472-8222
• DOI: https://doi.org/10.1517/14728222.2010.522347
• URN:NBN: urn:nbn:hr:105:130016
• Publication: 2010-10
• Document URL: https://doi.org/10.1517/14728222.2010.522347
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-27 19:11:06