Increased apoptosis at the late stage of tendon healing

Abstract

The mechanism for the clearance of excess healing fibroblasts at the end of tendon healing has not been reported despite the importance of maintaining tissue homeostasis. This study investigated the role of apoptosis in cell turnover in a rat central 1/3 patellar tendon donor site injury model. At days 4, 7, 14, 28, months 2 and 6, the rats were killed. Patellar tendons without injury served as control. Apoptotic cells were determined by an in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay and anti-active caspase-3 antibodies, while proliferating cells were determined by anti-proliferating cell nuclear antigen antibodies. The total fibroblast-like cell density in the center of the wound increased from day 4 and thereafter steadily returned to normal. In situ TUNEL assay showed few positive staining cells in the wound at days 4 and 7. The percentages of TUNEL-positive fibroblast-like cells showing morphological characteristics of apoptosis increased sharply and reached the maximum on day 28 (median %: 31.38%). No fibroblast-like cell was stained at month 6 and the healed tissue was similar to that in a normal uninjured tendon. A similar trend was observed with active caspase-3 immunohistochemistry. In conclusion, an increase in apoptosis at the end of tendon healing coincided with a decrease in cellularity.

Tendon Healing with Growth Factors

“…Loading and mobilization of the tendon seem to decrease the expression of TGF-β (Eliasson et al, 2009), possibly reducing the initial inflammation in the healing tendon. At the end stage of tendon healing TGF-β may also promote the apoptosis of fibrocytes (Jorgensen et al, 2005;Lui et al, 2007). In our one studies we observe a high concentration of TGF-β initially, which then decreased for 2 and 4 weeks and then increase massively at 8 weeks, possibly reflecting the initial inflammation and activation of cells, followed by an intermediary period and then the remodeling of the tendon with increased apoptosis of no longer necessary cells.…”

Chondrocyte Phenotype and Ectopic Ossification in Collagenase-induced Tendon Degeneration

“…After deparaffination, the sections were stained with hematoxylin-eosin. IHC was done as described previously (Fu et al 2003;Lui et al 2007). Briefly, after removal of paraffin and rehydration, the sections were decalcified with 9% formic acid for 10 min and washed for 1 min.…”

Complete Achilles Tenotomy: A New Improved Experimental Surgical Technique in Rats

“…The cell density could be elevated by six to sevenfold during tendon healing [27]. Our microscopic findings describe the tendon healing process after a complete rupture, showing a trend to cellular proliferation and fibrilogenesis two weeks after injury.…”