Moderate Exercise Mitigates the Detrimental Effects of Aging on Tendon Stem Cells

• Published in: PloS one Vol. 10; no. 6; p. e0130454
• Main Authors: Zhang, Jianying, Wang, James H-C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.06.2015; Public Library of Science (PLoS)
• Subjects: Aging; Aging (artificial); Animal models; Animals; Calcification; Cell culture; Cell Differentiation; Cell Proliferation; Cells (biology); Cells, Cultured; Collagen; Collagen (type I); Degeneration; Fibroblasts; Fitness equipment; Gene expression; Gene Expression Regulation; Genes; Hypotheses; In vivo methods and tests; Laboratories; Mice; Morphology; Nucleostemin; Oct-4 protein; Patellar Ligament - cytology; Patellar Ligament - metabolism; Patellar Ligament - ultrastructure; Physical Conditioning, Animal; Physical training; Progenitor cells; Running; Stem cell transplantation; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Stress, Mechanical; Stretching; Tendons; Weight-Bearing; United States > US; Pittsburgh Pennsylvania; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0130454

Aging is known to cause tendon degeneration whereas moderate exercise imparts beneficial effects on tendons. Since stem cells play a vital role in maintaining tissue integrity, in this study we aimed to define the effects of aging and moderate exercise on tendon stem/progenitor cells (TSCs) using in vitro and in vivo models. TSCs derived from aging mice (9 and 24 months) proliferated significantly slower than TSCs obtained from young mice (2.5 and 5 months). In addition, expression of the stem cell markers Oct-4, nucleostemin (NS), Sca-1 and SSEA-1 in TSCs decreased in an age-dependent manner. Interestingly, moderate mechanical stretching (4%) of aging TSCs in vitro significantly increased the expression of the stem cell marker, NS, but 8% stretching decreased NS expression. Similarly, 4% mechanical stretching increased the expression of Nanog, another stem cell marker, and the tenocyte-related genes, collagen I and tenomodulin. However, 8% stretching increased expression of the non-tenocyte-related genes, LPL, Sox-9 and Runx-2, while 4% stretching had minimal effects on the expression of these genes. In the in vivo study, moderate treadmill running (MTR) of aging mice (9 months) resulted in the increased proliferation rate of aging TSCs in culture, decreased lipid deposition, proteoglycan accumulation and calcification, and increased the expression of NS in the patellar tendons. These findings indicate that while aging impairs the proliferative ability of TSCs and reduces their stemness, moderate exercise can mitigate the deleterious effects of aging on TSCs and therefore may be responsible for decreased aging-induced tendon degeneration.