|
A gene in the load-sensing machinery of bone may hold the key to developing new drugs for brittle bone disorders like osteoporosis in adults or osteogenesis imperfecta (OI) in children.
In bones, cells called osteocytes sense mechanical stress, like that caused by exercise, and in response call for other cells called osteoblasts to start producing more bone tissue, giving the bones greater density and strength. A team of researchers led by Matthew Warman, MD, of Children's Orthopedic Research Laboratories, has engineered mice with unusually dense bones using mutations in a gene called Lrp5 (which is part of the osteocytes' stress-sensing system) that cause high bone mass in people.
"These high bone mass mutations seem to fool the osteocytes, the most mature bone cells, into thinking they hadn't made enough bone tissue," said Dr. Warman. "These results tell us that targeting mature bone cells might be enough to increase bone mass and treat diseases like osteoporosis and other skeletal fragility disorders."
The model is helping Dr. Warman and others understand the precise role Lrp5 plays in turning strain into bone, information that could have strong implications for pharmaceutical companies seeking to develop drugs for osteoporosis and other diseases characterized by skeletal fragility. "In fact," Dr. Warman notes, "several companies are pursuing these strategies, and our data provides strong support for continuing this line of investigation."
Dr. Warman is particularly interested in figuring out whether tricking osteocytes could help children with OI. The osteoblasts in these children don't properly produce type 1 collagen, a protein that acts like a scaffold for bone growth. As a result, their bones remain exceedingly brittle and prone to fracture. Dr. Warman believes it may be possible to use Lrp5 to work around the collagen defect and help at least some of these children grow stronger bones, a concept he is already starting to pursue in the laboratory.
More information: on.chbos.org/pv0811bones
|
