Myofibroblast cells are preferentially expressed early in a rabbit model of joint contracture

Abstract

Studies have demonstrated increased myofibroblasts in contractures. However, the timeline is largely unknown. The aim of this study was to determine the number of myofibroblasts in contracting joint capsules at 3-time points over a 24-week period. Eighteen rabbits subjected to a surgical procedure designed to elicit a knee joint contracture were divided into three groups of six. Rabbits were sacrificed at each respective time point and myofibroblasts in the joint capsules were quantified using immunohistochemistry. The percent of myofibroblasts was significantly elevated in the operated limbs compared to the control limbs at 2 weeks (20% vs. 7%, respectively; p ¼ 0.014). There was no difference in the percent of myofibroblasts between the operated and control limbs at 8 or 24 weeks (p ¼ 0.96 and 0.07, respectively). The percent of myofibroblasts dropped from 20% at 2 weeks to 3.0% at 8 weeks (p < 0.001). The decrease from 8 to 24 weeks was not significant (p ¼ 0.19). A large proportion of myofibroblasts are present in contracted joints at 2 weeks. By week 8, the proportion of myofibroblasts seem to return to normal. Interventions aimed at affecting the myofibroblast cell in order to prevent fibrosis should be instituted early. ß

Temporary Presence of Myofibroblasts in Human Elbow Capsule After Trauma

“…In contrast to these findings is a recent study by Abdel and colleagues showing that myofibroblast cells are only expressed early in a rabbit model of joint contracture and return to normal in chronic stages of posttraumatic joint contractures 37 . As Hildebrand and colleagues evaluated the initiation of the process in the early stages of the rabbit model, the authors mentioned that this type of study would not be possible in humans 40 .…”

“…T emporal myofibroblast differentiation in human elbow capsules after acute trauma and in the posttraumatic period has not been described 37 . Increased proliferation of fibroblasts and production of extracellular matrix in the posttraumatic elbow capsule result in a thick, scarred joint capsule that can limit elbow motion clinically 10,11 .…”

“…Our data do not eliminate a causative relation between myofibroblasts and elbow contractures. However, they suggest that any potential interventions to inhibit or limit myofibroblast proliferation should start early (within weeks after injury) 37 , as myofibroblasts are not present in the chronic (contracture) phase. We further speculate that aggressive stretching as an early intervention by means of continuous passive motion 51 or dynamic splinting 7,8 might be counterproductive in the first two weeks, as myofibroblast differentiation is known to be upregulated by mechanical tension 48,49,52 .…”

“…Indeed, myofibroblasts and one of their key inducing growth factors (TGF-b) have been reported to be elevated in both human elbow joint contracture capsules [34][35][36] as well as in a rabbit contracture model [37][38][39][40] . In related clinical studies, myofibroblasts are believed to be responsible for capsular contraction in posttraumatic arthrofibrosis of the knee 41 with subsequent loss of motion.…”

Effect of pERK2 on extracellular matrix turnover of the fibrotic joint capsule in a post-traumatic joint contracture model

“…By contrast, other animal models of post-traumatic immobilization have revealed reversible joint motion loss following periods of remobilization equal to the duration of initial immobilization (9)(10)(11), bringing into question the unique pathological changes occurring following trauma that render the joint susceptible to irreversible joint contractures. Based on previous studies in animals and humans, joint capsule fibrosis observed in post-traumatic joint contractures may account for this irreversible loss of joint motion; myofibroblasts are considered to be the cell type predominantly involved in the development of joint capsule fibrosis (12)(13)(14), and elbow extension-flexion motion is inversely proportional to the number of myofibroblasts present within the capsule of the elbow joint (15). A previous study using the current model also supports this hypothesis, as the joint capsules from rats of the ORC group were densely filled with myofibroblasts (7).…”