Bone formation goes with the gut, study finds

[Guest guest]

Colleagues, the following is FYI and does not necessarily reflect my own

opinion. I have no further knowledge of the topic. If you do not wish to

receive these posts, set your email filter to filter out any messages

coming from @nutritionucanlivewith.com and the program will remove

anything coming from me.

---------------------------------------------------------

Public release date: 26-Nov-2008

http://www.eurekalert.org/pub_releases/2008-11/cp-bfg112008.php

Contact: Cathleen Genova

cgenova@...

Cell Press

Bone formation goes with the gut, study finds

When it comes to remodeling our bones—an ongoing process of break down

and renewal that goes on throughout adulthood--researchers have new

evidence that our guts play a surprisingly important role. The findings

point toward novel methods for increasing bone mass in patients with

diseases characterized by impaired bone formation, including

postmenopausal osteoporosis, according to the report in the November

26th issue of the journal Cell, a Cell Press publication.

" 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. "

Too much serotonin released by the gut leads to a decline in bone mass;

too little and bones bulk up beyond what is normal, their study shows.

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. Just what that serotonin did, however, had remained

a matter of considerable debate.

The current study was aimed at clearing up the role of a gene that

encodes LDL-receptor related protein 5 (LRP5), one of the most intensely

studied regulators of bone remodeling. Patients with a genetic mutation

that leads to a loss of that protein's function have a rare disease

known as osteoporosis pseudoglioma (OPPG), characterized by a severe

decline in bone formation and other symptoms. Other, presumably

activating, mutations in LRP5 cause high bone mass syndrome. " That

different mutations in this gene cause two bone diseases of opposite

nature underscores the critical importance in the regulation of bone

formation of the pathway or pathways controlled by Lrp5, " the

researchers said.

Earlier studies had suggested LRP5 might operate on bone through one

developmental pathway, but Karsenty's team wasn't convinced that was the

whole story. They've now confirmed that hunch.

They find that the bones of 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.

Further study showed 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.

Although the findings were made in mice, Karsenty says they have direct

application to understanding bone remodeling in humans, and to the

development of treatments designed to increase bone mass.

" This is not a mouse story, " Karsenty said. " From the beginning it was

a human story that we've now worked out in the mouse. "

The findings suggest that OPPG and high bone mass syndrome are actually

more gut- than bone-originating diseases. It also provides an

explanation for another observation: that patients with autism who have

high blood serotonin levels often have osteoporosis. Patients taking

synthetic serotonin reuptake inhibitors (SSRIs) chronically, a class of

antidepressant drugs that increase extracellular serotonin

concentration, can also have reduced bone mass, the researchers noted.

They emphasized however, that it's too soon to say whether this new

connection between gut serotonin and bone will explain that side effect

of the drugs or not.

So, given the gut's newfound pull over bone, might diet play a role?

While the researchers did show in mice that a diet low in the

tryptophan—the raw ingredient for serotonin's manufacture--can have an

effect on bone mass, at least in the Lrp5-deficient mice, Karsenty

thinks that serotonin inhibiting drugs are a more likely method than

diet for building bone mass in people. Coincidentally, however, one of

the highest sources of tryptophan is the Thanksgiving turkey.

###

The researchers include Vijay K. Yadav, Columbia University, New York,

NY; Je-Hwang Ryu, Columbia University, New York, NY; Nina Suda, Columbia

University, New York, NY; Kenji F. Tanaka, Columbia University, New

York, NY; Jay A. Gingrich, Columbia University, New York, NY; Gunther

Schutz, German Cancer Research Center, Heidelberg, Germany; Francis H.

Glorieux, Shriners Hospital for Children, McGill University, Montreal,

Canada; Cherie Y. Chiang, University of Melbourne, Heidelberg,

Australia; D. Zajac, University of Melbourne, Heidelberg,

Australia; Karl L. Insogna, Yale School of Medicine, New Haven, CT; J.

Mann, Columbia University, New York, NY; Rene Hen, Columbia

University, New York, NY; Ducy, Columbia University, New York,

NY, and Gerard Karsenty, Columbia University, New York, NY.

--

ne Holden, MS, RD

" Ask the Parkinson Dietitian " http://www.parkinson.org/

" Eat well, stay well with Parkinson's disease "

" Parkinson's disease: Guidelines for Medical Nutrition Therapy "

http://www.nutritionucanlivewith.com/