The Effect of Kalirin on Bone in Mice

Osteoporosis affects 50% of women and 20% of men, which may lead to bone fracture. There are three major bone cell types. The primary function of osteoclasts is bone resorption, while osteoblasts work to form bone. Once osteoblasts complete their purpose, they become embedded in the bone matrix and become osteocytes, bone cells which regulate the activity of osteoblasts and osteoclasts. The different bone cells and their functions allow efficient bone homeostasis, but an imbalance can cause diseases such as osteoporosis. Kalirin, a GTP-exchange factor protein, is expressed in osteoclasts, osteoblasts, and osteocytes, but its role is unknown. Kalirin deficiency has been found to be associated with a decrease in bone mass in humans and mice. To understand the impact of Kalirin within osteoblasts and osteocytes, mice were genetically modified to delete Kalirin from these cells. Mice were studied through the analysis of bone mass by micro-CT and by histology to examine osteocyte number and viability. Data shows that the deletion of Kalirin leads to unexpectedly high bone mass and low survival rates in osteocytes. Given that osteocytes are important in bone quality, their increased levels of apoptosis when Kalirin is deleted suggests Kalirin may regulate bone quality.

Supervisor: Dr. Angela Bruzzaniti
Department: Biomedical Sciences and Comprehensive Care