Joint capsule matrix turnover in a rabbit model of chronic joint contractures: Correlation with human contractures

Abstract

To evaluate changes in matrix molecules of the joint capsule, the right knees of 24 skeletally mature female NZW rabbits were immobilized while the contralateral limb served as an unoperated control. The immobilization was discontinued at 8 weeks and the rabbits were divided among four groups (n ¼ 6) based on the number of weeks the right knees were remobilized: 0, 8, 16, or 32. Three rabbits (six knees) that did not have operations provided normal control joint capsules. The mRNA levels for collagen types I, II, and III, and MMP-1 and -13 were significantly increased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. In contrast, the mRNA levels for TIMP-1, -2, and -3 were decreased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. The mRNA levels for lumican and decorin were increased in the joint capsules of the contracture knees in all groups when compared to normal capsules. Many of the changes observed in this animal model are similar to those observed in human joint capsules from posttraumatic elbow contractures, supporting the value of this rabbit model. ß

Cellular, matrix, and growth factor components of the joint capsule are modified early in the process of posttraumatic contracture formation in a rabbit model

“…In a few cases, there were some significant time-related effects in the contracture capsule. Our findings regarding the changes in these molecules in the joint capsule during the acute stages are similar to the changes observed in the chronic stages of the rabbit knee model of posttraumatic contractures, and to those in chronic human elbow contractures published previously by our laboratory (Hildebrand et al 2004a(Hildebrand et al , b, 2005(Hildebrand et al , 2006(Hildebrand et al , 2007. In the current study on the acute stages in our animal model of posttraumatic contractures, we did not measure the joint contractures mechanically.…”

“…The pattern of early changes in levels of myofibroblasts, matrix molecules, and enzymes and growth factors in the joint capsules of injured and immobilized rabbit knees is similar to what has been observed in chronic contractures of the human elbow joint and in the chronic stages of the present animal model (Hildebrand et al 2004a(Hildebrand et al , b, 2005(Hildebrand et al , 2006(Hildebrand et al , 2007. It appears that the contracture process is turned on early during the acute phase and that it does not subsequently revert to baseline conditions in more chronic stages, as has been described in a healing ligament (Frank et al 1983).…”

“…Quantification of mRNA was done following methods described previously (Hildebrand et al 2004b(Hildebrand et al , 2006. The TRIspin method was used for isolation of total RNA (Reno et al 1996) and the yield was determined fluorometrically.…”

“…PCR was performed using the Life Technologies kit (Life Technologies, Gaithersburg, MD). Rabbit-specific primers were used, as published previously (Hildebrand et al 2006(Hildebrand et al , 2007. Primer sets were optimized for PCR cycles, and linear amplification curves were plotted.…”

“…Changes in the human elbow joint capsule in chronic posttraumatic contractures have recently been characterized and correlated with chronic changes in a newly developed rabbit knee model of posttraumatic contractures (Hildebrand et al 2004a(Hildebrand et al , b, 2005(Hildebrand et al , 2006(Hildebrand et al , 2007. The joint capsule abnormalities followed similar patterns in both cases.…”