Tendon overuse pathology : clinical and laboratory studies

• Main Author: Scott, Alexander
• Format: Others
• Language: English
• Published: University of British Columbia 2009
• Online Access: http://hdl.handle.net/2429/5621

Background: Painful tendon overuse pathology (tendinosis) is poorly understood. The objectives were to identify major cell populations within clinical tendinosis lesions, and to examine factors involved in the regulation of tendon cell death, survival, or proliferation. The overarching hypothesis was that both cell death and cell proliferation play roles in the development of tendinosis. Methods: 1: Chronic patellar tendinosis tissue was compared with normal, pain-free patellar tendon using Western blot, immunohistochemistry and in situ hybridization. A variety of cell types were examined in relation to relevant features of soft tissue injury and repair including cellular proliferation and versican expression. 2: In adult male rats, early tendinosis was induced in the supraspinatus tendon by 4-16 weeks of mechanical loading (eccentric exercise). Tendons were analyzed morphologically using polarized light and transmission electron microscopy, and by immunolabeling for molecular markers of proliferation and survival. 3: The influence of IGF-I on tenocyte survival was tested in response to chronic hypoxia in a cell-culture setting. Results 1: Tendinosis was characterized by proliferation of tenocytes, endothelial cells, and smooth muscle cells within a versican-enriched extracellular matrix. Mast cells were also more numerous in patient biopsies, whereas macrophages and lymphocytes were virtually absent. VEGF expression was increased in endothelial cells from tendinosis tendons and was more marked in patients with shorter symptom duration. 2: Mechanical loading of the rat supraspinatus tendon by downhill running caused focal tendon lesions characterized by tenocyte proliferation, collagen disarray and glycosaminoglycan accumulation. Tenocytes in these areas of injury demonstrated a proliferative response which correlated with IGF-I expression and phosphorylation of ERK-l/2and IRS-1. 3: Prolonged hypoxia of primary tenocyte cell cultures resulted in tenocyte apoptosis and caspase activation. Apoptosis could be prevented dose-dependently by IGF-I, which activated the PKB survival pathway Conclusions The current studies outlined predominant cell populations present in tendinosis lesions and identified factors which may be involved in regulating their death, survival and activity. These experiments have opened up new avenues of research into the pathophysiology of tendinosis.