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| The leg bone of a normal mouse (left) is compared to a leg bone of a mouse with high levels of the signaling protein WNT7B. The pink middle in the picture at right indicates more bone cells.--Courtesy of Washington University School of Medicine |
A newly discovered mechanism that promotes bone growth could lead to novel treatments for osteoporosis, which affects an estimated one in three women and one in 12 men in the U.S.
Overall, about 55% of Americans over 50 have osteoporosis, which causes millions of fractures each year.
Scientists at Washington University School of Medicine in St. Louis have found that the mTOR pathway, which is responsible for interpreting a cell's surrounding environment and nutritional and energy status, is involved in spurring bone formation.
Specifically, investigators found that one of the WNT family of proteins--called WNT7B--dramatically enhances bone formation, and it works through mTOR, which has previously not been well-studied in bone. WNT proteins are responsible for carrying messages into cells and regulating 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.
Principal investigator Fanxin Long, a professor of orthopedic surgery at the Washington University School of Medicine, explained that mTOR can determine whether a cell should go into a mode to produce things like proteins or new bone.
"Bone formation is an energetically expensive process, so it makes sense that some regulator would tell a cell whether there is sufficient energy and material to manufacture new bone," Long said in a statement.
By studying mice with normal levels or mice engineered to produce an extra amount of WNT proteins, Long and his colleagues discovered that the WNT7B protein helps stimulate bone growth. The engineered mice that made more WNT7B than normal mice increased the number of bone-manufacturing cells and consequently manufactured new bone at much higher rates.
The findings were published Jan. 30 in PLOS ONE.
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 bonemaking (osteoblast) cells fluctuates, while the number of bone-degrading (osteoclast) cells also adjusts.
Long and his colleagues hope to identify more specific targets in the bone-formation process so that drugs could be developed to stimulate bone formation in people with osteoporosis without causing unwanted side effects.
- read the press release
- see the study