CX3CL1 and CX3CR1 Expressing Tendon Cells – A novel Immune Cell Population in the Tendon Core

Abstract

Tendon disorders frequently occur and recent evidence has clearly implicated the presence of immune cells and inflammatory events during early tendinopathy. However, the origin and properties of these cells remain poorly defined. Therefore, the aim of this study was to determine the presence of myleoid cells in healthy rodent and human tendon tissue and to characterize them. Using various transgenic reporter mouse models, we demonstrate the presence of tendon cells in the dense matrix of the tendon core expressing the fractalkine (Fkn) receptor CX3CR1 and its cognate ligand CX3CL1/Fkn. Pro-inflammatory stimulation of 3D tendon-like constructsin vitroresulted in a significant increase in the expression of IL-1β, IL-6, Mmp3, Mmp9, Cx3cl1, and epiregulin which has been reported to contribute to inflammation, wound healing, and tissue repair. Furthermore, we demonstrate that inhibition of the fractalkine receptor blocked tendon cell migrationin vitroand show the presence of CX3CR1/CX3CL1/EREG expressing cells in healthy human tendons. Taken together, we demonstrate the presence of CX3CL1+/CX3CR1+ “tenophages” within the healthy tendon proper potentially fulfilling surveillance functions in tendons.Summary StatementHere, we demonstrate the presence of a macrophage-like, CX3CL1/CX3CR1-expressing cell population within the healthy tendon proper potentially fulfilling a surveillance function.

Extrinsic Macrophages Protect While Tendon Progenitors Degrade: Insights from a Tissue Engineered Model of Tendon Compartmental Crosstalk

“…Also, core‐resident “tenophage” or “tenoclast” populations have recently been gaining more attention as potential role players in early tendinopathy, especially in combination with increased expression of Tnf‐α, Il‐6 , Mmp‐3 , and Mmp‐9 . [ 44,46,49–52 ] If we complement our flow cytometry data with the gene‐level increase of these markers in the extrinsic compartment of rapidly degrading core//progenitor tenostructs, (initially core‐resident but outward‐migrating) tenophages are likely to be involved in the observed core explant degeneration. [ 46 ]…”