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

Zhang J, Wang JH - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Cytochemical analysis of the non-tenocyte differentiation of TSCs from young (2.5 months) and aging (9 months) mice (G-L).TSCs were analyzed for their ability to undergo multi-differentiation by incubating in specific differentiation induction media and staining with Oil Red O (G, H), Safranin O (I, J) and Alizarin Red S (K, L). Evidently, young TSCs in culture differentiated more extensively into adipocytes (G), chondrocytes (I), osteocytes (K) than their counterparts—aging TSCs (H, J, L). Semi-quantitation (M) of the positively stained regions was performed by analyzing 12 different images of each tendon section. Data are mean ± SD, and *P < 0.05, compared to young TSCs.
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pone.0130454.g004: Cytochemical analysis of the non-tenocyte differentiation of TSCs from young (2.5 months) and aging (9 months) mice (G-L).TSCs were analyzed for their ability to undergo multi-differentiation by incubating in specific differentiation induction media and staining with Oil Red O (G, H), Safranin O (I, J) and Alizarin Red S (K, L). Evidently, young TSCs in culture differentiated more extensively into adipocytes (G), chondrocytes (I), osteocytes (K) than their counterparts—aging TSCs (H, J, L). Semi-quantitation (M) of the positively stained regions was performed by analyzing 12 different images of each tendon section. Data are mean ± SD, and *P < 0.05, compared to young TSCs.

Mentions: Our second approach was in vitro, where we induced TSCs, isolated from young and aging mice, to differentiate into non-tenocytes by culturing the cells in non-tenogenic induction media. Cytochemical staining showed that young TSCs stained heavily for Oil Red O (Fig 4A), Safranin O (Fig 4C) and Alizarin Red S (Fig 4E) compared to TSCs from aging mice (Fig 4B, 4D, 4F). Semi-quantification (Fig 4G) also confirmed such an increase and further revealed that the extent of Oil Red O and Safranin O staining in young TSCs were higher by ~3-fold each and that Alizarin Red S staining was higher by ~1.5 fold. These results indicate that when compared to young TSCs, aging TSCs have lower potential to differentiate into non-tenocytes in vitro suggesting a decline in the quality of TSCs in aging mice.


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

Zhang J, Wang JH - PLoS ONE (2015)

Cytochemical analysis of the non-tenocyte differentiation of TSCs from young (2.5 months) and aging (9 months) mice (G-L).TSCs were analyzed for their ability to undergo multi-differentiation by incubating in specific differentiation induction media and staining with Oil Red O (G, H), Safranin O (I, J) and Alizarin Red S (K, L). Evidently, young TSCs in culture differentiated more extensively into adipocytes (G), chondrocytes (I), osteocytes (K) than their counterparts—aging TSCs (H, J, L). Semi-quantitation (M) of the positively stained regions was performed by analyzing 12 different images of each tendon section. Data are mean ± SD, and *P < 0.05, compared to young TSCs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4472753&req=5

pone.0130454.g004: Cytochemical analysis of the non-tenocyte differentiation of TSCs from young (2.5 months) and aging (9 months) mice (G-L).TSCs were analyzed for their ability to undergo multi-differentiation by incubating in specific differentiation induction media and staining with Oil Red O (G, H), Safranin O (I, J) and Alizarin Red S (K, L). Evidently, young TSCs in culture differentiated more extensively into adipocytes (G), chondrocytes (I), osteocytes (K) than their counterparts—aging TSCs (H, J, L). Semi-quantitation (M) of the positively stained regions was performed by analyzing 12 different images of each tendon section. Data are mean ± SD, and *P < 0.05, compared to young TSCs.
Mentions: Our second approach was in vitro, where we induced TSCs, isolated from young and aging mice, to differentiate into non-tenocytes by culturing the cells in non-tenogenic induction media. Cytochemical staining showed that young TSCs stained heavily for Oil Red O (Fig 4A), Safranin O (Fig 4C) and Alizarin Red S (Fig 4E) compared to TSCs from aging mice (Fig 4B, 4D, 4F). Semi-quantification (Fig 4G) also confirmed such an increase and further revealed that the extent of Oil Red O and Safranin O staining in young TSCs were higher by ~3-fold each and that Alizarin Red S staining was higher by ~1.5 fold. These results indicate that when compared to young TSCs, aging TSCs have lower potential to differentiate into non-tenocytes in vitro suggesting a decline in the quality of TSCs in aging mice.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus