My Internship
SITE SUMMARY
My internship position through LHSI is with Dr. Angela Bruzzaniti is mainly focused on working to understand bone mass. The research looks heavily at osteoclasts, osteoblasts, and osteocytes and their roles that work together to break down and repair bone. Kalirin is a GTP-exchange factor protein expressed in the different bone cells that is believed to play a key role in how bone gets rebuilt.
OUR RESEARCH
Kalirin is a very important guanine nucleotide exchange factor that plays a large role in both regulating the function of osteoclasts and osteoblasts as well as bone mass. Osteoclasts are the cell in the bone that break down old bone while osteoblasts are the cells that replace and rebuild new bone. Osteocytes are another type of bone cell that are formed from osteoblasts and are the most prominent cells. They have been found to regulate the function of osteoclasts and osteoblasts. The methodology listed below was used to study the bone in mice with normal levels of Kalirin and those with Kalirin deleted to see the impact this compound has on bone.
Osteocyte Count
Slides with mouse vertebrae were examined under a microscope at 20x and stained to determine which cells were living or dead. Those with a blue hue were still alive and functioning whereas those with a partial or complete brown hue were considered dying/dead. The control and experimental groups' data was compared to see how the levels of apoptosis were effected.
PROJECT ABSTRACT
Bone loss affects billions, and it is estimated that 50% of women and 20% of men will experience a bone fracture related to osteoporosis in their lifetime. The different bone cells and their functions allow efficient bone homeostasis, but an imbalance between the two can causes diseases related to inconsistent bone density. The primary function of osteoclasts is bone resorption, which works with osteoblasts, who work to reform 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. Kalirin, a GTP-exchange factor protein that is expressed in osteoclasts, osteoblasts, and osteocytes, has been found to be associated with bone loss in humans and mice. To understand the impact Kalirin has within the skeletal system, mice were genetically modified to delete Kalirin from osteoblasts and osteocytes. Mice were studied through analysis of bone mass and by the number of osteocytes and their viability. Data shows that the deletion of Kalirin leads to low survival rates in osteocytes and unexpectedly high bone mass. These findings suggest that the deletion of Kalirin indicates poor bone quality and changes in bone mass.
