Disrupted Cellularity in Partial Tendon Enthesis Injury of Fibrillin-1 Deficient Mice

Introduction: The tendon enthesis is the site of tendon-bone attachment and includes four zones: tendon, uncalcified fibrocartilage, calcified fibrocartilage, and bone. Enthesis injuries demonstrate impaired healing due to this complex cellular architecture. Previous research has shown TGF-β upregulation worsens tendon enthesis healing. Mutations in Fibrillin-1 lead to an increase and dysregulation of TGF-β tissue levels. However, it is unknown how tendon enthesis healing may be affected in transgenic Fibrillin-1 transgenic mice, which our study aimed to explore.

Methods: Using Fibrillin-1 transgenic mice, we performed a partial horizontal incision at the Achilles tendon enthesis site. Using the contralateral leg as a sham control, we harvested the enthesis site at postoperative (POD) 3, 7, 14, and 28. Histological analyses were conducted using Movat’s modified pentachrome staining to assess tissue architecture, distinct stratification of enthesis zones, and the linear alignment of collagen and cells at the enthesis site.

Results: Injured Fibrillin-1 mice showed greater disruption of collagen organization at the enthesis site compared to the uninjured controls across all postoperative days, especially POD7. Specifically, there was a marked loss of linear organizations of cells and a diminished definition within the injured four enthesis zones, particularly within the calcified fibrocartilaginous zone.

Conclusion: These findings highlight the cellular alterations that occur during tendon enthesis healing in the setting of increased TGF-β bioavailability. Future research should compare these findings to wildtype mice and investigate the gene expression changes that are responsible for these modifications in tissue architecture to inform targets for enhancing tendon healing.