Discovery may lead to new drugs for osteoporosis

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Washington: Scientists have found that activating a biological pathway may help stimulate bone growth.

Scientists at Washington University School of Medicine said the finding could lead to new treatments for osteoporosis, a progressive bone disease that is characterised by a decrease in bone mass and density which can lead to an increased risk of fracture.

"We have been looking for new ways to stimulate bone formation," said principal investigator Fanxin Long.

"The tools we already have are very good at slowing the breakdown of bone, but we need better ways to stimulate new bone growth," Long said.

Long studied mice and focused on a pathway involved in bone formation. The so-called WNT proteins carry messages into cells and regulate embryonic and adult tissue in mammals, including humans.

The WNT proteins enter cells from the outside and then can activate multiple pathways inside those cells.

A specific member of the WNT family of proteins dramatically enhances bone formation, and it works through a mechanism that has not been well-studied in bone before, researchers said.

It's called the mTOR pathway, and it interprets a cell's surrounding environment, and nutritional and energy status.

"By analysing that information, mTOR can determine whether a cell should go into a mode to make lots of stuff, like proteins or, in this case, new bone," said Long.

Long and his colleagues studied mice that made either normal levels or an extra amount of WNT proteins.

 

They found that a particular WNT protein, WNT7B, is a potent stimulator of bone formation in mice. Mice engineered to make additional WNT7B manufactured new bone at much higher rates than normal mice.

The researchers also found that the protein created more bone by greatly increasing the number of bone-manufacturing cells in the mice.

Our bones are in a constant state of flux as the number of bone-making (osteoblast) cells fluctuates, while the number of bone-degrading (osteoclast) cells also adjusts.

The WNT7B protein had no effect on the total activity of bone-degrading osteoclasts but substantially increased the number of bone-building osteoblast cells. And it did so by stimulating the mTOR pathway.

"It's still early, but our finding seems to point out that activating the mTOR pathway may be a good way to stimulate bone growth," said Long.

"This is a new twist because much of the current focus in mTOR-related drug development has been on compounds that inhibit the pathway to shut down cancer cells," Long said.

The study is published in the journal PLOS Genetics.  

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