Scientists have discovered a protein naturally produced by the body that appears to be a potent stimulator of new bone growth. The finding could lead to the development of new drugs to treat osteoporosis and other diseases that occur when the body doesn’t make enough bone.
“We have been looking for new ways to stimulate bone formation,” said principal investigator Fanxin Long, PhD, Department of Orthopedic Surgery, Washington University School of Medicine, in St. Louis, Missouri. “The tools we already have are very good at slowing the breakdown of bone, but we need better ways to stimulate new bone growth.”
Osteoporosis is caused by a decline in mineral bone density, which makes bones weaker and more likely to fracture. Postmenopausal women are especially vulnerable to osteoporosis and are more likely to experience rapid bone loss.
The disease affects over half of Americans age 50 and older. One in three women and one in 12 men are believed to have osteoporosis, which causes 1.5 million fractures annually, mostly in the hips, wrist or lower back.
In studies on mice, Long and his research team focused on a pathway – called the mTOR pathway – which regulates tissue and bone formation in mammals, including humans. So-called WNT proteins carry messages into cells and interpret a cell’s nutritional and energy status.
“By analyzing 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,” explained Long, a professor of orthopaedic surgery.
“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.”
The researchers studied mice that had either normal levels of WNT proteins or an extra amount; and found that a particular protein, WNT7B, greatly increasing the number of bone-manufacturing cells. Mice engineered to make additional WNT7B manufactured new bone at much higher rates than normal mice.
“The human bone tissue is of considerable regenerative capacity as reflected in bone remodeling and in fracture healing. However, bone tissue regeneration deteriorates with age, and tremendous unmet medical needs exist for safe and effective strategies to stimulate bone formation in older individuals commonly inflicted with osteoporosis or osteopenia,” said Long.
“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. 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.”
Drugs that inhibit the mTOR pathway are also used to suppress the immune response in patients after undergoing organ transplants. Interestingly, bone problems are common in those patients.
Long plans to look more deeply at the mechanism at the way WNT proteins stimulate bone cells to produce new bone. If more specific targets can be identified in the bone-formation process, drugs potentially could be developed to naturally stimulate bone formation in people with osteoporosis.