MYOFIBROBLASTS IN THE HEALING LAPINE MEDIAL COLLATERAL LIGAMENT - POSSIBLE MECHANISMS OF CONTRACTION

The specific objective of this study was to determine the chronology o f the appearance of the myofibroblast in the healing ligament. The ove rall goal of our work is to elucidate the cellular mechanism of contra ction in this tissue. The myofibroblast has been found to be responsib le for wound contraction in many tissues and to be the cause of the co ntracture in several pathological conditions. This cell type contains the actin isoform previously thought to be unique to smooth muscle cel ls and displays certain characteristic features at the ultrastructural level. In 26 New Zealand White male rabbits, the right medial collate ral ligament was transected, whereas the left medial collateral ligame nt received a sham operation. The central third of the ligament (ligam ent scar tissue) was evaluated at 2, 3, 6, 8, 10, and 12 weeks postope ratively by immunohistochemical techniques, transmission electron micr oscopy, and Western blot analyses. Three other rabbits served as anato mic controls. During the early reparative phase (2 and 3 weeks after t ransection), there was an increase in the number of cells containing a lpha-smooth muscle actin as well as augmentation of the alpha-smooth m uscle actin content within each cell-a finding attributed to smooth mu scle cells and pericytes associated with neovascularity. No myofibrobl asts were detected at this stage, immediately postoperatively, or in t he sham-operation controls. Ligaments in the remodeling phase of heali ng (6, 8, 10, and 12 weeks) exhibited alpha-smooth muscle actin in fib roblasts (myofibroblasts) as well as in vascular pericytes and smooth muscle cells. During this stage of healing, transmission electron micr oscopy demonstrated an increase in the number of cells displaying myof ibroblastic features. It was estimated that at 12 weeks of healing 10% of the cells at the site of injury were myofibroblasts. This is the f irst definitive finding of myofibroblasts in the injury site of the he aling ligament, to our knowledge. The appearance of myofibroblasts in the 6-12 week healing period, the interval during which the ligament h as been shown to contract in studies by other investigators, is a rati onale for a hypothesis that a cellular contractile apparatus comprisin g or-smooth muscle actin (i.e., the myofibroblast) may contribute to t he recovery of original ligament length (and normal in situ strain).