LRP5 gene may control bone density, potentially leading to osteoporosis treatments
Flipping a genetic switch that controls specialized cells in human bone may one day be an effective way to reverse osteoporosis, according to researchers at the Children's Hospital Boston.
Their study, which contained significant contributions from scientists in Indiana, Ohio, Texas, Germany and the Netherlands, focused on one particular subsection of human DNA called low-density lipoprotein receptor-related protein 5 (LRP5).
Previous studies have associated LRP5 mutations with high bone mass disorders, as opposed to low bone mass conditions like osteoporosis.
In this new investigation, published in the journal Nature Medicine
, scientists set out to determine what effect the LRP5 gene can have if it is upregulated, or turned on, in some bones but not in others.
The team already knew from prior studies that this genetic region appears to control the formation of new bone by regulating osteocytes. Unlike osteoblasts, the relatively young cells that produce new bone matrix, the similar but older bone tissue-producing osteocytes reside within the matrix itself.
To examine the effect of upregulating LRP5, researchers switched on the gene in selected bone sites in laboratory rodents.
Specifically, the team turned on the gene in osteocytes found within the animals' leg bones. They left those in the mice's vertebrae alone.
Sites given the genetic treatment eventually hardened, thickened and grew more dense, while the others remained relatively weak. Researchers concluded that the effects of LRP5 expression remain localized, staying within range of the mature osteocytes affected by the upregulation process.
Additionally, the study took into account the effects of this process on the body's serotonin levels, and vice versa. Serotonin is a neurotransmitter in the brain, though it is also found in the intestines and elsewhere throughout the body.
A study appearing in a 2008 issue of the journal Cell
came to the conclusion that LRP5 improves bone density by increasing the amount of serotonin found in the gastrointestinal tract.
In the new report, researchers found no connection between serotonin and LRP5, indicating that the gene affects bone growth through osteocytes, rather than by way of neurotransmitters in the gut.
Lead author Matthew Warman concluded that manipulation of LRP5 holds great promise in the ongoing fight against osteoporosis, although he tempered this notion by pointing out the differences between the study's sample and humans suffering from progressive bone loss.
"In our mice, the LRP5 mutations causing increased bone mass were present at birth, whereas if we want to design therapies that could improve bone strength in adults with osteoporosis...we would need to study the effect of inducing the [high bone mass] mutations in aged mice, instead of newborn mice," Warman noted.
The National Osteoporosis Foundation estimates that the female body creates as much as 90 percent of its adult bone mass by the age of 18, while the male body has largely completed its rapid bone production by the age of 20.
The organization states that after those ages, adults steadily lose bone mass at a rate of about 1 percent each year.