Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia

Fry, Christopher S.; Lee, Jonah D.; Mula, Jyothi; Kirby, Tyler J.; Jackson, Janna R.; Liu, Fujun; Yang, Lin; Mendias, Christopher L.; Dupont‐Versteegden, Esther E.; McCarthy, John J.; Peterson, Charlotte A.

doi:10.1038/nm.3710

Cited by 381 publications

(381 citation statements)

References 44 publications

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“…However, neither investigation completely eliminated satellite cells. In addition, genetic ablation of Pax7‐expressing cells caused deletion of satellite cells early in their myogenic lineage (Fry et al, 2015), while the current investigation caused significant reductions in satellite cell numbers only in older mice, apparently by biasing them toward a more differentiated state. Thus, the relationship between satellite cell numbers and sarcopenia may be influenced by the presence of injury, the magnitude and age at which satellite cell numbers are reduced and by the method used for their reduction.…”

Section: Discussionmentioning

confidence: 52%

“…Although the age‐related decline in satellite cell number contributes to the reduced regenerative capacity of injured, aging muscle (Brack, Bildsoe, & Hughes, 2005; Fry et al, 2015), whether satellite cell loss is sufficient to cause reduction in muscle mass in uninjured, aging muscle is controversial. Targeted ablation of Pax7+ satellite cells that produced a lifelong reduction in satellite cell numbers by approximately 70%–90% did not increase sarcopenia in sedentary mice (Fry et al, 2015) and findings in the current study show that satellite cell numbers can be reduced by about 45% in aging muscle, which leads to a reduction in sarcopenia. However, neither investigation completely eliminated satellite cells.…”

Section: Discussionmentioning

confidence: 99%

“…Together, these changes lead to increased risk of falling, loss of physical independence, and increased morbidity and mortality (Landi et al, 2012; Patel et al, 2014; Xue, Walston, Fried, & Beamer, 2011). Although sarcopenia is influenced by intrinsic changes in muscle (Sousa‐Victor et al, 2014) and by extrinsic factors from other systems (Carlson & Faulkner, 1989; Fry et al, 2015), the specific mechanisms that drive sarcopenia are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Myeloid cell‐derived tumor necrosis factor‐alpha promotes sarcopenia and regulates muscle cell fusion with aging muscle fibers

et al. 2018

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Sarcopenia is age‐related muscle wasting that lacks effective therapeutic interventions. We found that systemic ablation of tumor necrosis factor‐α (TNF‐α) prevented sarcopenia and prevented age‐related change in muscle fiber phenotype. Furthermore, TNF‐α ablation reduced the number of satellite cells in aging muscle and promoted muscle cell fusion in vivo and in vitro. Because CD68+ macrophages are important sources of TNF‐α and the number of CD68+ macrophages increases in aging muscle, we tested whether macrophage‐derived TNF‐α affects myogenesis. Media conditioned by TNF‐α‐null macrophages increased muscle cell fusion in vitro, compared to media conditioned by wild‐type macrophages. In addition, transplantation of bone marrow cells from wild‐type mice into TNF‐α‐null recipients increased satellite cell numbers and reduced numbers of centrally nucleated myofibers, indicating that myeloid cell‐secreted TNF‐α reduces muscle cell fusion. Transplanting bone marrow cells from wild‐type mice into TNF‐α‐null recipients also increased sarcopenia, although transplantation did not restore the age‐related change in muscle fiber phenotype. Collectively, we show that myeloid cell‐derived TNF‐α contributes to muscle aging by affecting sarcopenia and muscle cell fusion with aging muscle fibers. Our findings also show that TNF‐α that is intrinsic to muscle and TNF‐α secreted by immune cells work together to influence muscle aging.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Myeloid cell‐derived tumor necrosis factor‐alpha promotes sarcopenia and regulates muscle cell fusion with aging muscle fibers

et al. 2018

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“…Once damage occurs, satellite cells became activated and triggered the regeneration and reconstruction of skeletal muscles (Charge & Rudnicki, 2004; Collins et al., 2005; Meeson et al., 2004). A previous study indicated that muscle regeneration was attenuated due to the depletion of satellite cells in adult muscle (Fry et al., 2015). The molecular mechanism of this phenomenon remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Synergistic effects of TGFβ2, WNT9a, and FGFR4 signals attenuate satellite cell differentiation during skeletal muscle development

Zhang

et al. 2018

Aging Cell

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SummarySatellite cells play a key role in the aging, generation, and damage repair of skeletal muscle. The molecular mechanism of satellite cells in these processes remains largely unknown. This study systematically investigated for the first time the characteristics of mouse satellite cells at ten different ages. Results indicated that the number and differentiation capacity of satellite cells decreased with age during skeletal muscle development. Transcriptome analysis revealed that 2,907 genes were differentially expressed at six time points at postnatal stage. WGCNA and GO analysis indicated that 1,739 of the 2,907 DEGs were mainly involved in skeletal muscle development processes. Moreover, the results of WGCNA and protein interaction analysis demonstrated that Tgfβ2, Wnt9a, and Fgfr4 were the key genes responsible for the differentiation of satellite cells. Functional analysis showed that TGFβ2 and WNT9a inhibited, whereas FGFR4 promoted the differentiation of satellite cells. Furthermore, each two of them had a regulatory relationship at the protein level. In vivo study also confirmed that TGFβ2 could regulate the regeneration of skeletal muscle, as well as the expression of WNT9a and FGFR4. Therefore, we concluded that the synergistic effects of TGFβ2, WNT9a, and FGFR4 were responsible for attenuating of the differentiation of aging satellite cells during skeletal muscle development. This study provided new insights into the molecular mechanism of satellite cell development. The target genes and signaling pathways investigated in this study would be useful for improving the muscle growth of livestock or treating muscle diseases in clinical settings.

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“…In fact, a recent study clearly showed that the number of satellite cells decreases with age, and muscle regeneration is insufficient in aged mice 24) . However, this hypothesis has recently been challenged by two research groups independently, using a mouse model of ablated satellite cells in young adult muscle throughout the life of the animal 25,26) .…”

Section: Contribution Of Satellite Cells To Muscle Maintenance Duringmentioning

confidence: 99%

Role of satellite cells in skeletal muscle plasticity: Beyond muscle regeneration

Tamura

Furuichi

Manabe

et al. 2017

JPFSM

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Satellite cells are resident muscle stem cells located between the basal lamina and the plasma membrane of myofibers. They play crucial roles in muscle growth during the postnatal stage and muscle regeneration following postnatal development. However, the roles of satellite cells in adult muscles -in muscle growth, function, and adaptation -are poorly understood. Recently, by studying genetically engineered mice with conditionally ablated satellite cells, it has been reported that satellite cells play important roles in muscle growth and maintenance of muscle spindles or neuromuscular junctions, and produce growth factors that affect other organs. Here, we review the recent studies using tamoxifen-inducible Pax7-DTA mice and describe the novel roles of satellite cells in the maintenance of skeletal muscle plasticity.

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Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia

Cited by 381 publications

References 44 publications

Myeloid cell‐derived tumor necrosis factor‐alpha promotes sarcopenia and regulates muscle cell fusion with aging muscle fibers

Myeloid cell‐derived tumor necrosis factor‐alpha promotes sarcopenia and regulates muscle cell fusion with aging muscle fibers

Synergistic effects of TGFβ2, WNT9a, and FGFR4 signals attenuate satellite cell differentiation during skeletal muscle development

Role of satellite cells in skeletal muscle plasticity: Beyond muscle regeneration

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