Moving the target for osteoporosis treatment

A major axis that helps regulate the critical balance of bone production and loss has been found within bone cells, according to Medical College of Georgia researchers.

The finding provides a potential new target for treating debilitating osteoporosis and supports the evolving realization that most control of the constant cellular chatter that maintains healthy bone mass occurs in bone, not in the brain as previously believed, says Dr. Carlos M. Isales, endocrinologist.

"Probably the major component of bone regulation is local regulation," says Dr. Isales, who is presenting the findings at the 25th annual meeting of the American Society for Bone and Marrow Research Sept. 19-23 in Minneapolis.

He and colleagues at MCG, Yale University and the Department of Veterans Affairs Medical Center in Augusta have found that bone cells have all the components needed to regulate activity including a large molecule called POMC which makes a hormone called ACTH and its receptors.

ACTH was previously believed to exist mainly in the brain, where it regulates the adrenal gland's secretion of cortisol, another important hormone involved in maintaining blood pressure, electrolytes and blood sugar. "Cortisol is an important hormone for survival," says Dr. Isales. "It acts on the cell to stimulate production of a whole set of proteins that are important in cell survival and function. This was felt to be the main role for ACTH." Ironically, cortisol has a negative impact on bone, increasing bone-eating cells called osteoclasts and impairing calcium absorption.

But Dr. Isales and his colleagues serendipitously found ACTH is also secreted by osteoclasts and their bone-producing counterparts, osteoblasts, have ACTH receptors. And ACTH is very active within bone cells; in fact, his analysis of gene activity showed the expression of 714 genes was altered by ACTH.

"We now know it has multiple functions and one of them is making bone cel

Contact: Toni Baker
Medical College of Georgia

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