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Penn vet team uncovers a pathway that stimulates bone growth
Date:2/13/2013

has become clear that BMPs have some issues with safety and efficacy," Hankenson said. "In the field we're always searching for new ways for progenitor cells to become osteoblasts so we became interested in the Notch signaling pathway."

This molecular signaling pathway is found in most animal species and is known to play a role in stem cell differentiation. The researchers chose to investigate one of the proteins that acts in this pathway by binding to the Notch receptor, Jagged-1. The Penn Vet team has previously shown that Jagged-1 is highly expressed in bone-forming cells during fracture healing and that introducing Jagged-1 to mouse stem cells blocked the progression of stem cells to osteoblasts.

"That had been our operating dogma for a year or two," Hankenson said.

Next the researchers decided to see what happened when Jagged-1 was introduced to human stem cells. There they came upon a very different result.

"It was remarkable to find that just putting the cells onto the Jagged-1 ligand seemed sufficient for driving the formation of bone-producing cells," he said.

This finding aligns with other evidence linking Jagged-1 to bone formation. Patients with a rare disease known as Alagille syndrome frequently have mutations in the gene that codes for Jagged-1. Individuals with this condition have problems with their metabolism that severely affect their livers but also tend to have challenges with their skeletal system and break bones easily.

Furthermore, genome-wide association studies, which search large populations for mutations that may be linked with particular characteristics, have found a connection between mutations near the Jagged-1 gene and low bone mass.

Hankenson has multiple collaborations with other researchers at Penn to further investigate how manipulating the Jagged-1 protein may one day help patients. He is working with Kathleen Loomes of Penn's Perelman School of Medicine and the Ch
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Contact: Katherine Unger Baillie
kbaillie@upenn.edu
215-898-9194
University of Pennsylvania
Source:Eurekalert

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