The role of the FaS/FasL apoptotic pathway on osteoclastogenesis in the mouse model of controlled tibial fractures

master's thesis

• Author: Nina Lukač
• Mentor: Vedran Katavić (mentor)
• Committee member: Nataša Kovačić (predsjednik povjerenstva)
• Committee member: Zdravko Petanjek (član povjerenstva)
• Committee member: Vedran Katavić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2016-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Anatomy

Abstract

The Fas/FasL apoptotic system serves as a regulator of the immune system, but also has an influence on osteoclast survival and differentiation. The model of internally fixated controlled tibial fractures was used to evaluate its role on osteoclastogenesis in formation of new bone, as fracture healing serves as a model for embryonic skeletal development. The aim of this study was to evaluate the role of the apoptotic system on osteoclastogenesis in vivo, by evaluating the osteoclastogenic potential of different tissues; and in vitro, by analyzing the numbers of osteoclasts and eroded surface on histological sections of tibiae. The roles of Fas and FasL were investigated using knockout mice for the receptor and its ligand. We hypothesized that the number of osteoclasts would increase in the knockout strains because of a lacking of osteoclast apoptosis when Fas/FasL pathway is not functioning.
Observation of the histological sections of calluses in fractured tibiae confirmed that the healing of the fracture occurred by endochondral ossification. Our results showed that the loss of Fas or FasL caused an increase in the number of osteoclasts and the eroded surface in fracture calluses in the second week after the fracture, which was not observed in the B6 control. The analysis of osteoclasts on cartilage surfaces showed that the loss of Fas or its ligand did not cause a change in the number of osteoclasts on the cartilaginous part of the callus in the second week and did not cause a difference between the osteoclast numbers on the growth plate cartilage. The number of osteoclasts on those two cartilage surfaces did not differ between each other as well.
These results show that the Fas/FasL apoptotic system has a role in osteoclastogenesis during new bone formation, but further research is necessary to further elucidate its exact function.

• Keywords: bone; Fas; FasL; fracture; osteoclast
• Language: english
• URN:NBN: urn:nbn:hr:105:655501
• Study programme: Title: Medicine (in English language); Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-08-30 11:12:00