murine-hind-limb-explant-model-for-studying-mechanobiology-achilles

Murine Hind Limb Explant Model for Studying the Mechanobiology of Achilles Tendon Impingement

Tendon impingement upon bone generates a multiaxial mechanical strain environment with markedly elevated transverse compressive strain, which elicits a ...

University of Rochester

University of Rochester Medical Center

Despite the requirement for -lineage (Scx) cells during tendon development, the function of Scx cells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted Scx cells (ScxLin) prior to tendon injury and repair surgery and hypothesized that ScxLin mice would exhibit functionally deficient healing compared to wild-type littermates. Surprisingly, depletion of Scx cells resulted in increased biomechanical properties without impairments in gliding function at 28 days post-repair, indicative of regeneration. RNA sequencing of day 28 post-repair tendons highlighted differences in matrix-related genes, cell motility, cytoskeletal organization, and metabolism. We also utilized ScxLin mice to define the effects on post-natal tendon growth and adult tendon homeostasis and discovered that adult Scx cell depletion resulted in altered tendon collagen fibril diameter, density, and dispersion. Collectively, these findings enhance our fundamental understanding of tendon cell localization, function, and fate during healing, growth, and homeostasis.

Scleraxis-lineage cell depletion improves tendon healing and disrupts adult tendon homeostasis.

Immediately prior to inserting into bone, many healthy tendons experience impingement from nearby bony structures. However, super-physiological levels of impingement are implicated in insertional tendinopathies. Unfortunately, the mechanisms underlying the connection between impingement and tendon pathology remain poorly understood, in part due to the shortage of well-characterized animal models of impingement at clinically relevant sites. As a first step towards developing a model of excessive tendon impingement, the objective of this study was to characterize the mechanical strain environment in the mouse Achilles tendon insertion under passive dorsiflexion and confirm that - like humans - mice experience impingement of the tendon insertion from the calcaneus (heel bone) in dorsiflexed ankle positions. Based on previous work in humans, we hypothesized that during dorsiflexion, the mouse Achilles tendon insertion would experience high levels of transverse compressive strain due to calcaneal impingement. A custom-built loading platform was used to apply passive dorsiflexion, while an ultrasound transducer positioned over the Achilles tendon captured radiofrequency images. A non-rigid image registration algorithm was then used to map the transverse compressive strain based on the acquired ultrasound image sequences. Our results demonstrate that during passive dorsiflexion, transverse compressive strains were produced throughout the Achilles tendon, with significantly larger strain magnitudes at the tendon insertion than at the midsubstance. Furthermore, there was increasing transverse compressive strain observed within the Achilles tendon as a function of increasing dorsiflexion angle. This study enhances our understanding of the unique mechanical loading environment of the Achilles tendon under physiologically relevant conditions.

Keshia E. Mora

Department of Biomedical Engineering

University of Rochester

Murine Hind Limb Explant Model for Studying the Mechanobiology of Achilles Tendon Impingement

Keshia E. Mora

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University of Rochester

Murine Hind Limb Explant Model for Studying the Mechanobiology of Achilles Tendon Impingement

Department of Biomedical Engineering