Ablating hedgehog signaling in tenocytes during development impairs biomechanics and matrix organization of the adult murine patellar tendon enthesis.

Andrew P Breidenbach, Lindsey Aschbacher-Smith, Yinhui Lu, Nathaniel A Dyment, Chia-Feng Liu, Han Liu, Chris Wylie, Marepalli Rao, Jason T Shearn, David W Rowe, Karl E Kadler, Rulang Jiang, David L Butler

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Restoring the native structure of the tendon enthesis, where collagen fibers of the midsubstance are integrated within a fibrocartilaginous structure, is problematic following injury. As current surgical methods fail to restore this region adequately, engineers, biologists, and clinicians are working to understand how this structure forms as a prerequisite to improving repair outcomes. We recently reported on the role of Indian hedgehog (Ihh), a novel enthesis marker, in regulating early postnatal enthesis formation. Here, we investigate how inactivating the Hh pathway in tendon cells affects adult (12-week) murine patellar tendon (PT) enthesis mechanics, fibrocartilage morphology, and collagen fiber organization. We show that ablating Hh signaling resulted in greater than 100% increased failure insertion strain (0.10 v. 0.05 mm/mm, p

    Keywords

    • enthesis
    • fibrocartilage
    • hedgehog
    • mineralization
    • serial block face-scanning electron microscopy
    • tendon mechanics

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