Researchers have found ap rotein that could be used to develop new treatments for bone injuries.
Researchers in Michigan have zeroed in on a key protein and developed a new therapeutic approach to treat fractured bones that will not heal properly.
The new method delivers additional Jagged-1—a potent osteoinductive protein known to activate the Notch signaling pathway that regulates bone healing—at the location of a bone injury.
“We’ve hypothesized for many years that by binding the Jagged-1 to a biomaterial and delivering it to a bone injury site, we could enhance healing,” Kurt Hankenson, PhD, a professor of orthopaedic surgery at Michigan Medicine, said in a statement.
Occasionally, broken bones do not heal properly or quickly, despite the use of pins, plates or a cast to aid in the recovery. Bone morphogenetic proteins (BMP)— designed to promote spinal fusion and bone repair— don’t always offer a solution because the molecules can overperform and cause excessive or misdirected bone growth.
“Novel therapies have gone underdeveloped because of this assumption that bones heal without problem,” Hankenson said. “The reality is there’s a huge number of fractures that occur each year that don’t heal very well.”
During the study, the researchers found that rodents who received Jagged-1 through a wet collagen sponge saw improvements to skull and femoral bone injuries, while the rodents treated with BMPs benefited, but developed the same problematic bone hypertrophy associated with human use of the proteins.
The signaling of Jagged-1 is unique because this particular ligand typically binds to a delivery cell to activate bone healing in an adjacent cell—a vital trait to help ensure that a supplemental Jagged-1 dose, administered at the spot of injury, stays in place and carries out its intended function.
According to Hankenson, as a result bone will only form where bone is supposed to form.
BMPs, by comparison, are soluble, so they can migrate from the site of delivery and settle elsewhere in the body, triggering other cells that are not supposed to form bone.
However, because the body produces Jagged-1 on its own, new potential therapies would require a synthetic version of the ligand to be produced and administered to a patient.
“We do not think there is necessarily a deficiency,” Hankenson said. “But when we think about biological molecules delivered for therapy, we’re usually identifying something that’s there normally and trying to promote more activity by giving more of it.”
The study was published in npj Regenerative Medicine.
