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.

每年，有33％的美国公民患有肌肉骨骼疾病，需要医疗干预，每年的直接医疗费用接近1万亿美元。尽管骨骼功能障碍无处不在，但目前在临床使用中安全有效的骨骼生长因子有限。Notch是一种细胞间通信途径，可调节间充质/成骨细胞谱系中的自我更新和分化。骨骼中主要的Notch配体Jagged-1是一种有效的骨诱导蛋白，可正向调节动物创伤后骨骼的愈合。该报告描述了使用骨髓消融作为模型系统在膜内骨形成过程中Notch的时间调控，并证明了在间充质祖细胞中Jagged-1的破坏后，骨形成的减少。在胶原蛋白支架上使用重组的Jagged-1蛋白进行Notch功能获得可促进小鼠和大鼠颅面（颅骨）和阑尾（股骨）外科缺损的愈合。Jagged-1的局部递送促进了骨并置和缺陷愈合，同时避免了临床上有问题的骨形态发生蛋白的弥漫性骨肥大特征。结论是，Jagged-1是一种骨合成代谢药物，具有治疗外伤或先天性骨缺损的治疗潜力。同时避免了临床上有问题的骨形态发生蛋白的弥漫性骨肥大特征。结论是，Jagged-1是一种骨合成代谢药物，具有治疗外伤或先天性骨缺损的治疗潜力。同时避免了临床上有问题的骨形态发生蛋白的弥漫性骨肥大特征。结论是，Jagged-1是一种骨合成代谢药物，具有治疗外伤或先天性骨缺损的治疗潜力。