| Summary: | 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.
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