IU School of Dentistry oral biology professor Dr. Angela Bruzzaniti and one of her IU School of Medicine colleagues, Dr. Melissa Kacena of the Department of Orthopaedic Surgery, are using a new grant from the National Institutes of Health to study the process of bone formation and the complex series of signals involved in bone growth and bone loss – protein signals that have often been likened to “on” and “off” switches that regulate bone. The long-term goal of such research is to help in the development of treatment therapies for osteoporosis and other bone-loss diseases.
Drs. Bruzzaniti and Kacena are the principal investigators of a five-year Research Project Grant (RO1) awarded by the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases. The medical and dental schools share the grant, which will provide about $350,000 in funding annually between 2011 and 2016, for a total of more than $1.7 million.
The researchers work with osteoblasts, which are cells that make new bone. They are specifically interested in regulation of the osteoblast function by megakaryocytes (MKs), which are bone marrow cells that produce the blood platelets necessary for normal blood clotting. MKs interact with the osteoblasts and increase the number of osteoblast cells in bone, and therefore increase the amount of new bone formed.
The focus of the current study is on a protein kinase (enzyme) known as Pyk2, which serves as a catalyst in signal transmission in osteoblasts. The investigators have found that Pyk2 levels in osteoblasts are controlled by MKs. The researchers hypothesize that MKs promote bone formation by controlling Pyk2 function in osteoblasts. They have designed a three-part, 60-month research study to assess Pyk2’s various activities in osteoblasts as well as its role in mice. By studying the interaction of MKs and osteoblasts, and the proteins that control osteoblast growth, they hope to identify novel therapeutic approaches that stimulate bone formation for the treatment of debilitating bone diseases such as osteoporosis.
Dr. Bruzzaniti holds a Ph.D. from the University of Melbourne, Australia. She was a postdoctoral fellow at Johns Hopkins University School of Medicine, Department of Neuroscience, from 1997 to 2000. Prior to her appointment at IU in 2008, she had served since 2000 as an associate research scientist at Yale University School of Medicine in the department of Orthopaedics and Cell Biology.