Affiliation:
1. Department of Biomedical Engineering University of Delaware Newark Delaware USA
2. Institute of Anatomy University of Zürich Zürich Switzerland
3. Department of Orthopaedic Surgery University of Michigan Ann Arbor Michigan USA
4. Department of Mechanical Engineering University of Delaware Newark Delaware USA
5. Department of Developmental Biology Washington University School of Medicine St. Louis Missouri USA
Abstract
AbstractBackgroundTendons and ligaments attach to bone are essential for joint mobility and stability in vertebrates. Tendon and ligament attachments (ie, entheses) are found at bony protrusions (ie, eminences), and the shape and size of these protrusions depend on both mechanical forces and cellular cues during growth. Tendon eminences also contribute to mechanical leverage for skeletal muscle. Fibroblast growth factor receptor (FGFR) signaling plays a critical role in bone development, and Fgfr1 and Fgfr2 are highly expressed in the perichondrium and periosteum of bone where entheses can be found.Results and ConclusionsWe used transgenic mice for combinatorial knockout of Fgfr1 and/or Fgfr2 in tendon/attachment progenitors (ScxCre) and measured eminence size and shape. Conditional deletion of both, but not individual, Fgfr1 and Fgfr2 in Scx progenitors led to enlarged eminences in the postnatal skeleton and shortening of long bones. In addition, Fgfr1/Fgfr2 double conditional knockout mice had more variation collagen fibril size in tendon, decreased tibial slope, and increased cell death at ligament attachments. These findings identify a role for FGFR signaling in regulating growth and maintenance of tendon/ligament attachments and the size and shape of bony eminences.
Funder
Delaware Space Grant Consortium
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Center for Medical Rehabilitation Research
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institute of General Medical Sciences
National Science Foundation
University of Delaware Research Foundation
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