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Researcher elucidates role of bone as endocrine organ
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AUSTIN, Texas — Osteocalcin, a hormone produced in cells responsible for bone remodeling, may be the link connecting the mechanical function of bone with energy metabolism, reproduction and even learning and memory — in other words, bone is an endocrine organ, Gerard Karsenty, MD, PhD, said during the opening plenary session at the American Association of Clinical Endocrinologists Annual Scientific and Clinical Congress.
“What I would like to show you today is that there is no discontinuity between the mechanical function of bone ... and the endocrine functions of bone that were also survival tools and can now be harnessed for therapeutic purposes,” Karsenty, the Paul A. Marks, MD, Professor and chairman of the genetics and development department at Columbia University, told the audience here. Karsenty is also the 2017 recipient of the AACE Frontiers in Science Award.
Karsenty and colleagues hypothesized that hormones affecting energy metabolism should regulate bone mass. The researchers focused on the role of leptin, a hormone that can suppress appetite and favor fertility.
“If there is no food intake, there is osteoporosis in adults. And, as we know, gonadal failure causes bone loss,” Karsenty said. “So, putting these observations together ... we came up 15 years ago with a hypothesis that there must be a coordinated regulation of an endocrine nature — because the organs are not close to each other — of bone growth ... energy metabolism and reproduction.”
Through a series of mouse experiments, the researchers identified a novel, osteoblast-specific protein — osteocalcin — present in high levels in the general circulation that acted like a hormone.
“It has all the features of a hormone, and now we have to prove that it was one,” Karsenty said, referring to the discovery.
In a gain-of-function mouse model, the researchers determined that mice that produced increased osteocalcin were born hypoglycemic and died early; they had increased insulin secretion and sensitivity. Mice without osteocalcin were “the mirror image,” with hyperglycemia and hypoinsulinemia. Osteocalcin proved to be an insulin secretagogue, Karsenty said.
Additional mouse studies showed that osteoblasts quadrupled testosterone production by testis explants, and decreased osteocalcin was associated with small testes in vivo. This suggests that bone is important in male reproduction, Karsenty said.
The discovery that osteocalcin crosses the blood-brain barrier led to experiments indicating that bone may play a role in depression and anxiety and in memory and cognition, according to Karsenty.
“This is now how bone beyond osteocalcin looks: It regulates functions that are needed to survive in a hostile environment — working, running, memory, insulin sensitivity, adaptation to circumstance,” Karsenty said.
Asked by AACE president and session moderator Pauline Camacho, MD, to speculate on future clinical benefits of osteocalcin research, Karsenty said, “The first application that I see is for sarcopenia and for age-related memory loss ... those are the two applications I see as the most immediate.”– by Jill Rollet
Reference:
Karsenty G. But Why Bone? Presented at: AACE Annual Scientific and Clinical Congress; May 3-7, 2017; Austin, Texas.
Disclosures: Karsenty reports no relevant financial disclosures.