The purpose of this article was to determine mast cell and neuropeptide nerve fiber numbers in joint capsules in posttraumatic contractures, as elevated numbers have been implicated in other fibrotic and contracture conditions. Twelve skeletally mature rabbits had intraarticular cortical windows removed from the medial and lateral femoral condyles and the knee joint immobilized. The contralateral unoperated limb served as a control. Equal numbers of rabbits were sacrificed 4 weeks after surgery or 40 weeks after the first surgery that included 32 weeks of remobilization. Six patients with chronic posttraumatic elbow joint contractures and six age-matched organ donor controls free of elbow contractures were also studied. Joint capsule myofibroblast, mast cell, and neuropeptide containing nerve fiber numbers were assessed with immunohistochemistry. The numbers of myofibroblasts, mast cells, and neuropeptide containing nerve fibers expressed as a percentage of total cells were significantly greater in the contracture capsules when compared to the control capsules at all time points (p < 0.0001). The range of percentages for the three components in the contracture capsules versus the controls were 41-48% versus 9-10%, 44-50% versus 11-13%, and 45-50% versus 10-12% for the acute and chronic stages of the rabbit model and the chronic stages in the human elbows, respectively. These data support the hypothesis that a myofibroblast-mast cell-neuropeptide fibrosis axis may underlie some of the pathologic changes in the joint capsule in posttraumatic contractures. Approaches designed to manipulate this axis, such as preventing degranulation of mast cells, warrant further investigation.
Keywordscontracture; joint capsule; myofibroblasts; mast cells; neuropeptides Loss of joint motion, or joint contracture, is a common complication following injuries. 1 The joint capsule is a key contributor to the formation of contractures and surgical releases to improve joint motion invariably include its removal. 2 Although the anatomic importance of the joint capsule in the pathogenesis of joint contractures has been known for many years, only recently has there been description of the cellular changes associated with posttraumatic contractures. [3][4][5] It was determined that the myofibroblast, a specialized fibro-
CIHR Author ManuscriptCIHR Author Manuscript CIHR Author Manuscript blast expressing the contractile smooth muscle protein α-smooth muscle actin (α-SMA) and associated with contracture and fibrosis in many organ systems, is increased in numbers in joint capsules from posttraumatic contractures when compared to similar tissues from normal joints. [4][5][6] This is true for the chronic stages of posttraumatic contractures in human elbow joints and a rabbit knee model of posttraumatic contractures. [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...