Protein Gives Mice Super Skeletons
Blocks fat production, increases bone mass nearly four times
Betterhumans Staff
A protein that blocks the production of fat in mice also gives them a bone mass four times that of normal mice, hinting at new ways of treating osteoporosis in humans.
The engineered mice have increased levels of a protein called Wnt10b.
In 2004, Ormond MacDougald and colleagues at the University of Michigan Medical School reported that over-expression of Wnt10b in fat cells causes mice to have 50% less body fat and fewer fat cells.
MacDougald and colleagues have now shown that high levels of Wnt10b expression in bone marrow increases bone mass and density, which could have implications for treating such conditions as osteoporosis.
"This is the first identification of a specific signaling protein in the Wnt family that regulates bone formation," says MacDougald.
Pathway regulator
Wnt10b is part of a family of 19 proteins that regulate changes that take place as embryos develop.
Wnt10b appears to affect the fate of bone marrow stem cells that can become either fat cells or bone-forming cells.
It now appears that Wnt10b blocks the fat cell pathway and stimulates the bone-forming pathway. "Which means less fat and more bone," says MacDougald.
No age-related decline
The study involved transgenic mice bred from genetically engineered mouse eggs.
Comparing the bone density in the leg of the mice to that of normal mice, the researchers found that the transgenic animals had almost four times as much bone.
Otherwise, say the researchers, there didn't appear to be any abnormal features in the bone.
The super-skeleton mice also kept their high bone mass as they aged, and even mice with induced estrogen deficiency—a cause of bone loss in women—showed no bone loss.
"Because the transgenic mice have more trabecular bone, or bone within the marrow cavity, to begin with, they are doubly protected from the usual loss of bone density due to estrogen deficiency," says MacDougald.
Potential treatments
Further confirming the role of Wnt10b in bone formation, the researchers found that a strain of mice lacking the gene had 30% lower bone volume and bone mineral density than normal mice.
MacDougald now aims to unravel the molecular mechanism behind Wnt10b's bone-building effect.
"It's not only an important scientific question, it's important to the understanding and potential treatment of osteoporosis and other human diseases," he says. "Right now, there is a need for drugs on the market to stimulate new bone formation. Being able to activate Wnt signaling in bone marrow and osteoblasts might help prevent the loss of bone associated with aging or menopause."
The research is reported in the Proceedings of the National Academy of Sciences.
http://www.betterhumans.com/
Betterhumans Staff
A protein that blocks the production of fat in mice also gives them a bone mass four times that of normal mice, hinting at new ways of treating osteoporosis in humans.
The engineered mice have increased levels of a protein called Wnt10b.
In 2004, Ormond MacDougald and colleagues at the University of Michigan Medical School reported that over-expression of Wnt10b in fat cells causes mice to have 50% less body fat and fewer fat cells.
MacDougald and colleagues have now shown that high levels of Wnt10b expression in bone marrow increases bone mass and density, which could have implications for treating such conditions as osteoporosis.
"This is the first identification of a specific signaling protein in the Wnt family that regulates bone formation," says MacDougald.
Pathway regulator
Wnt10b is part of a family of 19 proteins that regulate changes that take place as embryos develop.
Wnt10b appears to affect the fate of bone marrow stem cells that can become either fat cells or bone-forming cells.
It now appears that Wnt10b blocks the fat cell pathway and stimulates the bone-forming pathway. "Which means less fat and more bone," says MacDougald.
No age-related decline
The study involved transgenic mice bred from genetically engineered mouse eggs.
Comparing the bone density in the leg of the mice to that of normal mice, the researchers found that the transgenic animals had almost four times as much bone.
Otherwise, say the researchers, there didn't appear to be any abnormal features in the bone.
The super-skeleton mice also kept their high bone mass as they aged, and even mice with induced estrogen deficiency—a cause of bone loss in women—showed no bone loss.
"Because the transgenic mice have more trabecular bone, or bone within the marrow cavity, to begin with, they are doubly protected from the usual loss of bone density due to estrogen deficiency," says MacDougald.
Potential treatments
Further confirming the role of Wnt10b in bone formation, the researchers found that a strain of mice lacking the gene had 30% lower bone volume and bone mineral density than normal mice.
MacDougald now aims to unravel the molecular mechanism behind Wnt10b's bone-building effect.
"It's not only an important scientific question, it's important to the understanding and potential treatment of osteoporosis and other human diseases," he says. "Right now, there is a need for drugs on the market to stimulate new bone formation. Being able to activate Wnt signaling in bone marrow and osteoblasts might help prevent the loss of bone associated with aging or menopause."
The research is reported in the Proceedings of the National Academy of Sciences.
http://www.betterhumans.com/
posted by Klip7 at
1:12 AM
