Metabolic Divergence of Aged Tenocytes: Insights into Tendinopathic Disease Progression 572 views

Chronic tendinopathies commonly affect physically active patients and can be both painful and debilitating. Clinical observations and research in the field suggest that the etiology of this disease encompasses a complex combination of overuse, injury, and aging. Chronic tendinopathy is characterized by a lack of tissue maintenance resulting in dysfunctional tissue composition with poor architectural organization. The degenerative tissue has altered mechanical properties and consequently, a propensity for a higher incidence of injury. The native tendon cell population serves as the primary regulator of structural (extracellular matrix) synthesis, remodeling, and repair. These cells are the primary therapeutic targets for non-operative means of alleviating tendinopathic pathology. We aimed to elucidate the role of tendon cell aging on chronic tendinopathy by studying cells that were isolated from tissues of older animals. In this investigation, progression of tendinopathy was identified in Achilles tendon from aged, 22-month old, rats. Primary tendon cell cultures from the older rats were characterized and these culture systems were utilized in two subsequent studies detailing age-dependent dysfunction. In the first study, the aged cells were examined for fundamental changes in glycolytic and oxidative function to examine the possibility of an age-dependent basis correlating energy metabolism and the lack of tissue maintenance. Although there is no definitive evidence for the role of mitochondrial dysfunction, cells from the older rats display a distinct glycolytic phenotype in comparison to the juvenile tendon cells. In the second study, cell-mediated regulation of tendon architecture was investigated more directly by examining the age-dependent activity of degradative enzymes responsible for architectural remodeling. We report age-dependent changes in matrix metalloproteinase activities that are consistent with age-related tendon pathology.

MS (Master of Science)

English

All rights reserved (no additional license for public reuse)

2013-04-19