Re‐establishment of cytoskeletal tensional homeostasis in lax tendons occurs through an actin‐mediated cellular contraction of the extracellular matrix

Abstract

Cytoskeletal tensional homeostasis is known to be an important factor in controlling catabolic gene expression in tendon cells. Loss of cell tension in lax rat tail tendon fascicles (RTTfs) has been associated with an upregulation of MMP-13 gene expression and protein synthesis. To determine the role of the actin cytoskeleton in re-establishing tensional homeostasis in lax tendons, RTTfs were allowed to freely contract in vitro for 8 days. The cultured RTTfs contracted rapidly, reaching 50% of their initial length by 3 days. This contraction was associated with the presence of a-smooth muscle actin positive cells within the tendon. Disruption of the actin network by cytochalasian D caused an immediate and significant elongation of the contracted RTTfs. Subsequent removal of the cytochalasian D re-initiated the contraction process. When lax RTTfs were allowed to contract between fixed clamps in culture and become taut, they demonstrated a marked decrease in MMP-13 staining intensity when compared to freely contracting RTTfs. The ability of native tendon cells to contract lax tendons and re-establish their homeostatic ''set point'' with respect to collagenase production may be an important mechanism in the recovery of tendons elongated by injury, surgical positioning, or cyclic, viscoelastic creep secondary to repetitive exercise. ß

Hypoxia inhibits primary cilia formation and reduces cell-mediated contraction in stress-deprived rat tail tendon fascicles

“…Prolonged catabolic degradation leads to degeneration of the material properties of the tendon 18 . Cell mediated contraction in tendons that are initially lax but fixed between two points has been shown to regain cellular homeostatic tension and inhibit collagenase protein synthesis 20 . Thus a hypoxic induced decrease in tendon cell-mediated contraction may delay or inhibit the ability of the tendon to regain cellular homeostasis and thus prolong the catabolic degradation that may lead to tissue degeneration.…”

“…When collagen fibrils are damaged, or become lax, and lose the ability to bear load the tendon cells associated with the damaged collagen fibrils lose their cellular homeostatic tension 17,18 . The loss of cellular tensional homeostasis induces catabolic Hypoxia inhibits primary cilia formation and reduces cell-mediated contraction in stress-deprived rat tail tendon fascicles processes associated with tendinopathy 17 and cilia elongation 19,20 . However, a cellular based contraction mechanism has been shown to recover tendon laxity and re-establish the cytoskeletal tensional homeostasis of these tendon cells 20 .…”

“…The loss of cellular tensional homeostasis induces catabolic Hypoxia inhibits primary cilia formation and reduces cell-mediated contraction in stress-deprived rat tail tendon fascicles processes associated with tendinopathy 17 and cilia elongation 19,20 . However, a cellular based contraction mechanism has been shown to recover tendon laxity and re-establish the cytoskeletal tensional homeostasis of these tendon cells 20 . This, in turn, allowed the tendon cells to recalibrate their catabolic gene expression and protein synthesis to its previous normal levels 20 .…”

High magnitude, in vitro, biaxial, cyclic tensile strain induces actin depolymerization in tendon cells

“…These alterations in cytoskeletal structure can also affect the mechanobiological response of the cells, as both changes in cell shape as well as the © C I C E d i z i o n i I n t e r n a z i o n a l i depolymerization of the actin cytoskeleton have been shown to influence collagenase gene expression 2,11,15 . Tendon cells are also capable of actively contracting their extracellular matrix through an alpha smooth muscle actin based mechanism 12,20 . This contraction can re-establish the cytoskeletal tensional homeostasis of these tendon cells in situ by recalibrating their mechanobiological set point with respect to collagenase protein synthesis 20 .…”

“…Tendon cells are also capable of actively contracting their extracellular matrix through an alpha smooth muscle actin based mechanism 12,20 . This contraction can re-establish the cytoskeletal tensional homeostasis of these tendon cells in situ by recalibrating their mechanobiological set point with respect to collagenase protein synthesis 20 .…”