Intraoperative delivery of the Notch ligand Jagged-1 regenerates appendicular and craniofacial bone defects
Year: 2017
Type: article
Abstract: Each year, 33% of US citizens suffer from a musculoskeletal condition that requires medical intervention, with direct medical costs approaching $1 trillion USD per year. Despite the ubiquity of skeletal dysfunction, there are currently limited safe and efficacious bone growth factors in clinical use. Notch is a cell-cell communication pathway that regulates self-renewal and differentiation within the mesenchymal/osteoblast lineage. The principal Notch ligand in bone, Jagged-1, is a potent osteoinductive protein that positively regulates post-traumatic bone healing in animals. This report describes the temporal regulation of Notch during intramembranous bone formation using marrow ablation as a model system and demonstrates decreased bone formation following disruption of Jagged-1 in mesenchymal progenitor cells. Notch gain-of-function using recombinant Jagged-1 protein on collagen scaffolds promotes healing of craniofacial (calvarial) and appendicular (femoral) surgical defects in both mice and rats. Localized delivery of Jagged-1 promotes bone apposition and defect healing, while avoiding the diffuse bone hypertrophy characteristic of the clinically problematic bone morphogenetic proteins. It is concluded that Jagged-1 is a bone-anabolic agent with therapeutic potential for regenerating traumatic or congenital bone defects.
Source: npj Regenerative Medicine
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: U.S. Department of Defense, University of Pennsylvania, Institute for Translational Medicine and Therapeutics, National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research, National Center for Research Resources, Congressionally Directed Medical Research Programs
Awards: Notch-induced intramembranous bone regeneration, G256492535, G2800195642, G4119534169, Institutional Clinical and Translational Science Award, G556100993, G5850682332, Enhancing Notch Activation for Improved Bone Regeneration, Disruption of CD47 signaling promotes healing in ischemic fractures and bone allografts, Overall: Resource-based Center for Musculoskeletal Disorders Research (Overall Application)
OpenAlex ID: W2774019875