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

Abstract

Background and purpose A recently developed animal model of posttraumatic contractures reflects the chronic stages of the human condition. To understand the initiation of the process, we evaluated the cellular, matrix, and growth factor changes in the joint capsule in the early stages of the animal model, which would not be possible in humans.Methods 18 skeletally mature rabbits had intraarticular cortical windows removed from the medial and lateral femoral condyles, and the knee joint was immobilized. The contralateral unoperated limb served as a control. Equal numbers of rabbits were killed 2, 4, and 6 weeks after surgery. Myofibroblast, mRNA, and protein determinations were done with immunohistochemistry, RT-PCR, and western blot, respectively.Results Myofibroblast numbers were statistically significantly elevated in the joint capsules of the experimental knees as compared to control knees. The mRNA and protein levels for collagen types I and III, matrix metalloproteinases 1 and 13, and transforming growth factor β1 were statistically significantly greater, and for tissue inhibitor of matrix metalloproteinases 1 significantly less, in the experimental capsules than in the control capsules.Interpretation The experimental joint capsule changes in the acute stages of posttraumatic contractures are similar to those in the chronic stages of the process in this model. Thus, it appears that the mechanisms that attenuate the acute stages of the response to injury are circumvented, contributing to a prolonged modulation of myofibroblast numbers, matrix molecules and growth factors, and leading to joint contractures.

Joint capsule mast cells and neuropeptides are increased within four weeks of injury and remain elevated in chronic stages of posttraumatic contractures

“…4,5,[24][25][26] The changes in these cellular, matrix molecule, and enzyme and growth factor profiles occur very early in the animal model, supporting the concept that the process leading to joint contractures starts very quickly after the inciting event. 7 The total cellularity in the joint capsules was similar in some cases comparing contracture to control samples or was significantly elevated in the contracture capsules, even in the chronic posttraumatic contractures. These findings are in contrast to what has been published for a healing medial collateral ligament (MCL) where cellularity increases in the first several weeks following injury (acute), but then markedly decreases over the next several months (chronic).…”

“…[3][4][5] Myofibroblast numbers are increased very early in the contracture process, as early as 4 weeks after injury, in this rabbit knee model. 7 The question remains as to what is contributing to this early and sustained increase in myofibroblast numbers.…”

“…[3][4][5] Myofibroblast numbers are increased very early in the contracture process, as early as 4 weeks after injury, in this rabbit knee model. 7 The question remains as to what is contributing to this early and sustained increase in myofibroblast numbers.One possibility contributing to the early and sustained increase in myofibroblast numbers is a mast cell-neuropeptide fibrosis axis as described in skin wound healing. 8 Mast cells are widely distributed throughout connective tissues, including skin and joint capsules.…”

Synovial membrane asks for independence

“…The main clinical problem involving the fibrous part of the joint capsule is posttraumatic stiffness. The affected joint capsule is characterised by irreversible biomechanical and biochemical fibrogenic changes strikingly similar to those observed in many other fibroproliferative human conditions [14,26].…”

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

“…In patients with chronic elbow contractures following trauma, the fibrotic joint capsule becomes markedly thickened and disorganized compared with normal elbows (2,3). Cellular, matrix, and growth factor components of the joint capsule are changed during the formation of fibrotic joint capsules in a post-traumatic contracture model (4). Multiple scientific groups are, therefore, investigating novel strategies to reduce joint capsule fibrosis in order to prevent joint contracture.…”