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Jagged-1 as a More Selective Signal to Spur Bone Regrowth

Researchers here report on a more selective way to trigger the accelerated or enhanced regeneration of bone tissue, delivering jagged-1 to injuries rather than the bone morphogenetic proteins (BMPs) that have been used in the past. It appears to cause fewer issues related to inappropriate excess bone growth, as it influences mechanisms that are more closely associated with the process of regeneration in response to damage. The delivery of signals rather than cells or pharmaceuticals to produce regeneration will be a growing theme in the years ahead, and the approaches will only grow in sophistication and degree of control. The advance here is a small step in the grand scheme of the possible and the plausible; it will be interesting to see how this part of the industry evolves over the next few decades.

When a patient breaks a bone, there's a possibility the fracture won't heal properly or quickly, and use of a restorative tactic known as bone morphogenetic proteins, or BMPs, is increasingly less likely. Designed to promote spinal fusion and bone repair more than a decade ago, these molecules can overperform, causing excessive or misdirected bone growth, studies have shown. But because bone-healing biological research has often been limited, few other options exist. "Novel therapies have gone underdeveloped because of this assumption that bones heal without problem. The reality is there's a huge number of fractures that occur each year that don't heal very well."

The divide recently inspired scientists to examine a new therapeutic approach. Their method: deliver additional Jagged-1 - a potent osteoinductive protein known to activate the Notch signaling pathway that regulates bone healing - at the spot 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." The results affirm that hunch: Rodents that received Jagged-1, applied via wet collagen sponge, saw improvements to skull and femoral bone injuries. Rodents treated with BMPs, by contrast, also benefited but developed the same problematic bone hypertrophy associated with human use of those proteins. Those findings suggest that the former therapy could one day benefit people.

It's not fully known why some bones don't heal the way they should - nor do scientists know whether a genetic component plays a role. What researchers have studied for years, meanwhile, is the capacity of the Jagged-1 ligand to promote bone-forming cells. The signaling 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 on task) to carry out its intended function. 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 aren't supposed to form bone.

Link: https://labblog.uofmhealth.org/body-work/boosting-a-key-protein-to-help-bones-wont-heal

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