PAPER 011: MODIFYING JOINT CAPSULE CELLS CONTRACTILE PROPERTIES

Abstract

Purpose: To determine if cells isolated from the rabbit joint capsule in post-traumatic joint contractures have altered responses to stimuli and inhibitors.

Method: The right knee of three rabbits had cortical windows removed from the femoral condyles followed by 4 weeks of immobilization, a recently developed model of post-traumatic contractures. The contralateral knee served as an unoperated control. Primary cells (2.5 × 105 cells/ml) isolated from the posterior capsule were mixed with neutralized bovine collagen solution and then cast into tissue culture plate wells. Gelation occurred overnight and then the cells were treated with 1% serum replacement (control), 10 ng/mL TGF-beta1, and the TGF-beta1 receptor kinase inhibitor SB431542 at 10 microM or 0.1 microM. Gel contraction was measured at 24 post release from the edges of the well using captured images of the gels and computer software.

Results: In all groups the contracture (injured) knees displayed significantly greater collagen gel contraction than control capsule cells. The addition of the TGF-beta1 increased, while SB431542 at the higher dose decreased, the extent of contraction by contracture and control cells. The TGF-beta1 contraction effect was neutralized by the addition of the inhibitor at the higher dose. In terms of sensitivity to the manipulations, the contracture capsule cells had greater responses to the stimulant and inhibitor.

Conclusion: This work is significant as this is the first description of joint capsule cell properties. In post-traumatic contractures, these cells have an intrinsically increased contraction ability at baseline conditions (serum replacement), and these cells also have heightened responses to TGF-beta1 and the TGF-beta1 receptor kinase inhibitor SB431542, a known pathway associated with fibrosis. These results support future work modifying this pathway directly, or by manipulating cells that liberate TGF-beta1. One such strategy would be to prevent mast cells from degranulating as they are a source of TGF-beta1 and other profibrotic growth factors, cytokines and enzymes.