Alpha-smooth muscle actin containing contractile fibroblastic cells in human knee arthrofibrosis tissue. Winner of the AGA-DonJoy Award 2003

Abstract

Introduction: Primary arthrofibrosis is of major concern after joint trauma or knee ligament surgery. The underlying mechanism in detail remains unclear. Highly differentiated fibroblastic cells, so-called myofibroblasts, express the actin isoform alpha-smooth muscle actin (ASMA) and have been found to play a major role in tissue contraction during wound healing and organ fibrosis. We therefore studied the expression of myofibroblasts in human primary knee arthrofibrosis tissue.

Materials and methods: Tissue samples were taken from the infrapatellar fat pad and intercondylar region of nine patients who underwent revision surgery due to arthrofibrosis after anterior cruciate ligament (ACL) reconstruction (study group). Control tissue was taken from five patients who underwent primary ACL reconstruction (control group I) and from eight patients, who underwent second-look arthroscopy after primary ACL reconstruction (control group II). ASMA containing fibroblasts were immunostained with a monoclonal antibody. Histomorphometry was performed for total cell amount, ASMA containing fibroblasts, and vessel cross-sections.

Results: The arthrofibrosis group showed a tenfold higher amount of ASMA containing myofibroblasts (23.4% vs. 2.3%) than in control group I. There was a significantly higher total cell count and lower vessel density than in control group I. Control group II showed an upregulation of myofibroblasts almost five times that in control group I; nevertheless there was no evidence of scar formation or tissue fibrosis.

Conclusions: Myofibroblasts are responsible for scar tissue contraction during wound healing. In arthrofibrosis tissue fibroblast contraction may be involved in tissue fibrosis and contraction with consecutive loss of motion. We found that myofibroblasts are upregulated in arthrofibrosis tissue. ACL reconstruction itself caused an up regulation of myofibroblast content. Nevertheless these patients did not show any clinical or histological signs of arthrofibrosis. Thus it is reasonable to assume that the ratio of myofibroblasts and total cell amount in connective tissue are responsible for the onset of arthrofibrosis. Address the expression of this highly differentiated cell type may therefore present a target for future therapeutic interventions.