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Dr. Raj Gopalakrishnan

Dr. Raj Gopalakrishnan's research in bone formation has implications for dentistry and broader applications, such as the treatment of osteoporosis and bone cancer.

Examining bone, not teeth

By Linda Raab

From eNews, November 11, 2005

When people think of the University of Minnesota's School of Dentistry, they naturally first think of teeth. For faculty, staff, and visitors alike, it's hard not to; even the high-rise Moos Tower building that houses the school is shaped like a "molar in the sky." For Raj Gopalakrishnan, an assistant professor in the Department of Diagnostic and Biological Sciences, his research is hardly all about teeth. The basic research he performs on bone biology does have implications for dental implants, periodontal health, oral pathology, oral surgery, endodontics, and orthodontics. But talk to him for a few minutes, and it becomes clear that his work pertains to the whole human body.

Gopalakrishnan, a board-certified oral pathologist, is primarily interested in mechanisms of bone formation; in particular, how molecules involved in the pathways that increase or decrease bone density are regulated and therefore may affect bone development. One major project currently underway in his laboratory is a study of parathyroid hormone (PTH) and its regulation of mineralization, or hardening, of bone that occurs as it matures.

"In the body, PTH is required to maintain calcium balance," says Gopalakrishnan. "If blood calcium levels decrease, the body signals to the parathyroid gland, which secretes PTH. The PTH travels to cells in bone and signals them to start to resorb bone. Calcium is released from [the resorbing] bone and returns blood calcium levels to normal."

Gopalakrishnan studies osteoblasts, the cells in the body that make bone, by growing them in culture dishes. In initial studies, when he added PTH to cultured osteoblasts, he found that the osteoblasts did not undergo mineralization. Through additional studies, he demonstrated that a particular inhibitor protein, called matrix Gla protein, was induced by PTH in cell culture and prevented mineralization from occurring in cultured osteoblasts.

"These studies are important because they help us to understand PTH's basic function and physiology," explains Gopalakrishnan. "But they are also relevant to hyperparathyroidism that can cause a chronic depression of blood calcium levels. One of the major complications of hyperparathyroidism is osteoporosis."

An intriguing aspect of this work, according to Gopalakrishnan, relates to the treatment of osteoporosis, which is an abnormal loss of bone density and weight that can cause pain, loss of physical height, and fractures. Although PTH has been shown in osteoblast cultures to inhibit mineralization and therefore bone formation, when PTH was given to humans and animals in a specific regimen, it actually increased bone formation. The Food and Drug Administration has recently approved the use of PTH for the treatment of osteoporosis. In addition, the use of PTH to regenerate bone is of potential interest to dentists, because preliminary results by others suggest that it could be used to build bone at sites where periodontal disease has caused bone loss.

To read a longer version of this story, including other studies conducted by Gopalakrishnan, see "Spotlight" by the Office of the Vice President for Research.