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Skeletal Involvement in Alagille Syndrome

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Alagille Syndrome

Abstract

Alagille syndrome results in a spectrum of skeletal abnormalities in patients. Distinct facies are pathognomonic for the disease, and butterfly vertebrae are common. Patients have reduced bone mass and a propensity to fracture. While some of these abnormalities are developmental, others may be associated with alterations in nutrition (malabsorption) and systemic metabolism during growth. Emerging data demonstrate that Notch signaling and Jagged1 in particular have direct effects on adult bone cells. Activating Notch signaling with Jagged1 in human cells promotes osteoblast differentiation. However, data in genetically modified mice suggests that the regulation of Jagged1-Notch on the skeleton is complex, and Notch signaling may have variable effects depending on the site of the bone and the differentiation status of the target cell. Excitingly, the most recent work in the field demonstrates that delivery of Jagged1 bound to biomaterials promotes bone formation. This has broad implications for treating Alagille syndrome patients with acute fractures as well as treating patients with osteopenia.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA

    Yadav Wagley, Troy Mitchell & Kurt Hankenson

  2. Department of Biology, Eastern Washington University, Cheney, WA, USA

    Jason Ashley

  3. Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Kathleen M. Loomes

  4. Department of Pediatrics, Children’s Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Kathleen M. Loomes

Authors
  1. Yadav Wagley
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  2. Troy Mitchell
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  3. Jason Ashley
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  4. Kathleen M. Loomes
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  5. Kurt Hankenson
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Corresponding authors

Correspondence to Kathleen M. Loomes or Kurt Hankenson .

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Editors and Affiliations

  1. Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada

    Binita M. Kamath

  2. Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Kathleen M. Loomes

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Wagley, Y., Mitchell, T., Ashley, J., Loomes, K.M., Hankenson, K. (2018). Skeletal Involvement in Alagille Syndrome. In: Kamath, B., Loomes, K. (eds) Alagille Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-319-94571-2_9

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  • DOI: https://doi.org/10.1007/978-3-319-94571-2_9

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  • Online ISBN: 978-3-319-94571-2

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