It takes gut to form a bone

November 27th, 2008 - 1:42 pm ICT by ANI  

Washington, Nov 27 (ANI): When it comes to bone formation, serotonin produced in gut has a major role to play, finds a new study.

The study led by Columbia University researchers have found that too much serotonin released by the gut leads to a decline in bone mass; too little and bones bulk up beyond what is normal.

” This is totally new,” said Gerard Karsenty of Columbia University.

“We had no clue that the gut had control over bone, and in such a powerful manner,” he added.

While serotonin is most familiar for its effects on the brain, 95 percent of all serotonin in the body is actually produced by the gut, Karsenty explained.

The researchers were studying the role of a protein known as LDL-receptor related protein 5 (or LRP5), one of the most intensely studied regulators of bone remodelling which causes osteoporosis pseudoglioma when mutated.

Other mutations in LPR5, which presumably cause overactivity leading to high bone mass syndrome.

The researchers found that mice lacking Lrp5 show a rise in the activity of an enzyme called tryptophan hydroxylase 1 (Tph1).

Tph1 limits the rate of serotonin production in the gut from the amino acid tryptophan. (Amino acids are the building blocks of proteins.) In other words, mice without Lrp5 have too much Tph1, leading them to overproduce gut serotonin.

The researchers found that decreasing serotonin blood levels normalizes bone formation and bone mass in Lrp5-deficient mice, and that gut- but not bone-specific Lrp5 inactivation decreases bone formation.

Moreover, gut-specific activation of Lrp5, or inactivation of Tph1, increases bone mass and prevents bone loss in mice who have had their ovaries removed, a condition that mimics menopause.

Karsenty said that the study they direct application to understanding bone remodelling in humans, and to the development of treatments designed to increase bone mass.

” This is not a mouse story. From the beginning it was a human story that we”ve now worked out in the mouse,” Karsenty said.

The study appears in the journal Cell, a Cell Press publication. (ANI)

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