Collagen gel contraction as a measure of fibroblast function in an animal model of subsynovial connective tissue fibrosis.

Abstract

Carpal tunnel syndrome (CTS) is a peripheral neuropathy characterized by non-inflammatory fibrosis of the subsynovial connective tissues (SSCT). A rabbit model of CTS was developed to test the hypothesis that SSCT fibrosis causes the neuropathy. We used a cell-seeded collagen-gel contraction model to characterize the fibrosis in this model in terms of cellular mechanics, specifically to compare the ability of SSCT cells from the rabbit model and normal rabbits to contract the gel, and to assess the effect of transforming growth factor-&#x3b2;1,which is upregulated in CTS, on these cells. SSCT fibrosis was induced in six retired breeder female rabbits which were sacrificed at 6 weeks (N&#x2009;=&#x2009;3) and 12 weeks (n&#x2009;=&#x2009;3). An additional two rabbits served as controls. SSCT was harvested according to a standard protocol. Gels seeded with SSCT cells from rabbits sacrificed at 6 weeks had significantly higher tensile strength (p&#x2009;<&#x2009;0.001) and Young's modulus (p&#x2009;<&#x2009;0.001) than gels seeded with cells from rabbits sacrificed at 12 weeks or control animals. TGF-&#x3b2;1 significantly increased the decay time constant (p&#x2009;<&#x2009;0.001), tensile strength (p&#x2009;<&#x2009;0.001), and Young's modulus (p&#x2009;<&#x2009;0.001) regardless of the cell source. This model may be useful in screening therapeutic agents that may block SSCT fibrosis, identifying possible candidates for CTS treatment.