FOR THE SUPPLEMENT Insertional Achilles tendinopathy (IAT) is a debilitating disorder with poor conservative (non-surgical) treatment outcomes. Insufficient understanding of the root cause of this pathology is a barrier to the development of effective interventions. Circumstantial evidence from prior studies by our group and others has implicated impingement by the calcaneus (heel bone) as the initiating cause of IAT. However, direct evidence that impingement triggers IAT-like biological adaptations in the Achilles tendon insertion is lacking. In the parent grant, we are we investigating how excised viable porcine and human tendon explants adapt in vitro to simulated impingement applied using a semi-customized, biaxial tension/indentation device. While this device provides close control over the strain environment, the effects of impingement in vivo may depend on specific anatomical features of the Achilles tendon insertion ? e.g., the angle and area of the Achilles tendon-calcaneus attachment, the presence of surrounding soft tissues, etc. ? that are absent in this model. To address this limitation, in Aim 1 of this supplement, we will establish a novel murine explant model of calcaneal impingement that preserves the native anatomy of the Achilles tendon insertion. Specifically, a custom-built platform developed by the supplement candidate will be used to apply controlled dorsiflexion (upward ankle rotation) to the hindpaw of a multi-tissue, intact mouse hindpaw explant, leading to contact between the Achilles tendon and calcaneus. The baseline tensile strain will be controlled by setting the extension angle of the knee in the device and the mechanical strain environment will be assessed through high frequency ultrasound elastography. We hypothesize that in this model ? as in the human ankle ? dorsiflexion induces progressive impingement of the Achilles tendon insertion as evidenced by the presence of localized transverse compressive strain at the site of contact between the calcaneus and the Achilles tendon. This hypothesis is supported by compelling preliminary data acquired by the supplement candidate.
In Aim 2 of this supplement, we will leverage the platform developed in Aim 1 to assess biological adaptations induced by impingement in the mouse hindlimb. We hypothesize that increased dorsiflexion angle (leading to impingement and increased transverse compressive strain in the Achilles tendon insertion) triggers elevated expression of fibrocartilage markers and enhanced formation of fibrocartilage. However, these effects are blunted by concomitant axial tensile strain in the Achilles tendon insertion generated by knee extension. The proposed experiments will elucidate if calcaneal impingement generates IAT-like tendon alterations in a model that preserves the native anatomy of the Achilles tendon insertion. Moreover, these studies will energize the supplement candidate's research potential by providing her with the opportunity to expand her research skills and acquire new knowledge relevant to her identified career path.
Insufficient understanding of the underlying cause of insertional Achilles tendinopathy (IAT) impedes the development of effective conservative (non-surgical) interventions for this pathology. To address this knowledge gap, this diversity supplement seeks to establish a novel murine explant model of calcaneal impingement ? a hypothesized trigger for IAT ? that preserves the native anatomy of the Achilles tendon insertion. Once established, this model will be deployed to assess biological adaptations induced by impingement in the mouse hindlimb and advance understanding of the root cause of IAT.
| Studentsova, Valentina; Mora, Keshia M; Glasner, Melissa F et al. (2018) Obesity/Type II Diabetes Promotes Function-limiting Changes in Murine Tendons that are not reversed by Restoring Normal Metabolic Function. Sci Rep 8:9218 |
