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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

Immunostaining of nucleostemin (NS) (A–C), semi-quantitation (D) and qRT-PCR analysis of gene expression (E, F) in aging TSCs subjected to mechanical loading in vitro.Patellar TSCs isolated from aging mice (9 months old) were subjected to no stretching (Control), 4% stretching or 8% stretching followed by the analyses. Immunostaining (A–C) and semi-quantitation (D) showed that compared to the control without stretching, 4% stretching increased the number of NS-expressing TSCs, whereas 8% stretching further decreased it. qRT-PCR analysis of the expression of three stem cell and tenocyte-related genes, Nanog, collagen I and tenomodulin (E) and three non-tenocyte related genes, LPL, Sox-9 and Runx-2 (F) showed that 4% stretching effectively up-regulated Nanog, collagen I and tenomodulin, but 8% was less effective (E). Moreover, while 4% stretching did not alter LPL and Runx-2 expression, and slightly up-regulated Sox-9 level, 8% stretching up-regulated the expression of all three genes (F). Data are mean ± SD, and *P < 0.05, compared to the respective controls. Bar—100 μm.
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pone.0130454.g005: Immunostaining of nucleostemin (NS) (A–C), semi-quantitation (D) and qRT-PCR analysis of gene expression (E, F) in aging TSCs subjected to mechanical loading in vitro.Patellar TSCs isolated from aging mice (9 months old) were subjected to no stretching (Control), 4% stretching or 8% stretching followed by the analyses. Immunostaining (A–C) and semi-quantitation (D) showed that compared to the control without stretching, 4% stretching increased the number of NS-expressing TSCs, whereas 8% stretching further decreased it. qRT-PCR analysis of the expression of three stem cell and tenocyte-related genes, Nanog, collagen I and tenomodulin (E) and three non-tenocyte related genes, LPL, Sox-9 and Runx-2 (F) showed that 4% stretching effectively up-regulated Nanog, collagen I and tenomodulin, but 8% was less effective (E). Moreover, while 4% stretching did not alter LPL and Runx-2 expression, and slightly up-regulated Sox-9 level, 8% stretching up-regulated the expression of all three genes (F). Data are mean ± SD, and *P < 0.05, compared to the respective controls. Bar—100 μm.

Mentions: To evaluate the effect of mechanical loading on aging, TSCs isolated from aging mice (9 months) were subjected to two levels of stretching that corresponded to low (4%) and high (8%) magnitudes. Such cyclic mechanical stretching in vitro was specifically designed to mimic in vivo mechanical loading conditions [24]. After the mechanical loading, immunocytochemical staining for NS was performed. Compared to the control (Fig 5A), the 4% stretched cells showed increased staining for NS (Fig 5B). However, after 8% stretching (Fig 5C) staining for NS was similar to the control (Fig 5A). Semi-quantitation of the NS positive cells showed that when compared to the control, 4% stretching led to a 38% increase in NS-positive TSCs, whereas 8% stretching resulted in a 29% decline in NS-positive TSCs (Fig 5D).


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

Zhang J, Wang JH - PLoS ONE (2015)

Immunostaining of nucleostemin (NS) (A–C), semi-quantitation (D) and qRT-PCR analysis of gene expression (E, F) in aging TSCs subjected to mechanical loading in vitro.Patellar TSCs isolated from aging mice (9 months old) were subjected to no stretching (Control), 4% stretching or 8% stretching followed by the analyses. Immunostaining (A–C) and semi-quantitation (D) showed that compared to the control without stretching, 4% stretching increased the number of NS-expressing TSCs, whereas 8% stretching further decreased it. qRT-PCR analysis of the expression of three stem cell and tenocyte-related genes, Nanog, collagen I and tenomodulin (E) and three non-tenocyte related genes, LPL, Sox-9 and Runx-2 (F) showed that 4% stretching effectively up-regulated Nanog, collagen I and tenomodulin, but 8% was less effective (E). Moreover, while 4% stretching did not alter LPL and Runx-2 expression, and slightly up-regulated Sox-9 level, 8% stretching up-regulated the expression of all three genes (F). Data are mean ± SD, and *P < 0.05, compared to the respective controls. Bar—100 μm.
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Related In: Results  -  Collection

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pone.0130454.g005: Immunostaining of nucleostemin (NS) (A–C), semi-quantitation (D) and qRT-PCR analysis of gene expression (E, F) in aging TSCs subjected to mechanical loading in vitro.Patellar TSCs isolated from aging mice (9 months old) were subjected to no stretching (Control), 4% stretching or 8% stretching followed by the analyses. Immunostaining (A–C) and semi-quantitation (D) showed that compared to the control without stretching, 4% stretching increased the number of NS-expressing TSCs, whereas 8% stretching further decreased it. qRT-PCR analysis of the expression of three stem cell and tenocyte-related genes, Nanog, collagen I and tenomodulin (E) and three non-tenocyte related genes, LPL, Sox-9 and Runx-2 (F) showed that 4% stretching effectively up-regulated Nanog, collagen I and tenomodulin, but 8% was less effective (E). Moreover, while 4% stretching did not alter LPL and Runx-2 expression, and slightly up-regulated Sox-9 level, 8% stretching up-regulated the expression of all three genes (F). Data are mean ± SD, and *P < 0.05, compared to the respective controls. Bar—100 μm.
Mentions: To evaluate the effect of mechanical loading on aging, TSCs isolated from aging mice (9 months) were subjected to two levels of stretching that corresponded to low (4%) and high (8%) magnitudes. Such cyclic mechanical stretching in vitro was specifically designed to mimic in vivo mechanical loading conditions [24]. After the mechanical loading, immunocytochemical staining for NS was performed. Compared to the control (Fig 5A), the 4% stretched cells showed increased staining for NS (Fig 5B). However, after 8% stretching (Fig 5C) staining for NS was similar to the control (Fig 5A). Semi-quantitation of the NS positive cells showed that when compared to the control, 4% stretching led to a 38% increase in NS-positive TSCs, whereas 8% stretching resulted in a 29% decline in NS-positive TSCs (Fig 5D).

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