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Notch: A Protein that Controls Bone Formation and Strength

Brendan Lee, M.D., Ph.D.
Department of Molecular and Human Genetics, Baylor College of Medicine
NIEHS Grant P01ES011253

Notch is a protein known to be involved in governing the determination of cell differentiation; however recent research supported by NIEHS at the Baylor College of Medicine shows that the protein also plays a critical role in bone formation and strength later in life. These findings have implications in understanding osteoporosis and diseases of disrupted bone formation.

The research shows that if there is an increase in Notch activity in bone cells, more bone is produced. Notch stimulated early proliferation of bone building cells known as osteoblasts. However, Notch knock-out mice exhibited age-related osteoporosis similar to that seen in humans. These animals also lost the ability to suppress bone resorption. Future studies will investigate whether the loss of Notch interferes with the signaling between osteoblasts and bone resorbing cells, osteoclasts, necessary for proper homeostasis between the activities of the two cell types.

This line of research began in patients who suffer from a condition called spondylocostal dysplasia, which is characterized by multiple malformations of the vertebrae and ribs coupled with clinical manifestations such as short neck, scoliosis, short trunk, and deformities of the rib cage. This research demonstrates the importance of integrative research—investigations that couple human diseases and conditions with basic laboratory studies. The researchers speculate that Notch and the cellular pathways that express and control it may be targets for drugs to treat debilitating and costly bone disorders such as osteopenia and osteoporosis.

Citation: Engin F, Yao Z, Yang T, Zhou G, Bertin T, Jiang MM, Chen Y, Wang L, Zheng H, Sutton RE, Boyce BF, Lee B. Dimorphic effects of Notch signaling in bone homeostasis. Nat Med. 2008 Mar;14(3):299-305.

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Last Reviewed: April 24, 2008