McMaster researchers pave the way to new drugs for bone diseases
Osteocalcin, a small bone-specific protein that influences bone formation, may facilitate the development of drugs to combat bone-related diseases, such as osteoporosis and bone metastases of cancer, say McMaster University researchers. Their study is to be published in the October 30 issue of Nature, a high-impact scientific journal.
Although it’s generally accepted that osteocalcin, discovered in 1976, binds to the mineral component of bone, called hydroxyapatite, the biological function and the 3-D structure of the protein have never been known. Now McMaster researchers have unlocked the mystery.
Osteocalcin is used as a biological marker for assessing bone disease and is closely linked to bone turnover, a fine balance between bone resorption and formation which goes on constantly during life.
“The 3-D structure of osteocalcin leads one to believe that the protein is the molecular marker or address of bone,” said biochemistry professor Daniel Yang.
It’s important to know the structure of the proteins because, if cells involved in bone metastasis and other bone diseases use the osteocalcin protein to identify where the bone is and where to attack, it may be possible to modify the structure through new drug therapies so that bone disease or metastasis does not set in.
“This is the result of seven years of hard work,” said Yang. “The crystal structure of osteocalcin provides, for the first time, an atomic model for the bone recognition mechanism of osteocalcin. It also allows us to speculate on the function of osteocalcin.”
Quyen Hoang, who worked on the research as a McMaster PhD student, said the study’s results provide essential tools to rationally design drugs that modulate the activity of osteocalcin and bone turnover.
Additionally, when bound to bone, part of osteocalcin is exposed to act as a magnet to recruit bone-processing cells to the bone surface to carry out bone resorption and formation.
“Based on the results of our study, we have designed some potential bone drugs and we are developing a method to screen for more,” said Hoang.
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