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.
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DOI：
10.1111/acel.12828
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发表时间：
2018-12
期刊：
影响因子：
7.8
通讯作者：
Tidball JG
中科院分区：
文献类型：
--
作者：
Wang Y;Welc SS;Wehling-Henricks M;Tidball JG
肌肉减少症是缺乏有效治疗干预的年龄相关性肌肉萎缩。我们发现，全身消融肿瘤坏死因子-α（TNF-α）可预防肌肉减少症，并预防肌纤维表型的年龄相关变化。此外，TNF-α消融减少了衰老肌肉中卫星细胞的数量，并促进了体内和体外肌细胞融合。由于CD 68+巨噬细胞是TNF-α的重要来源，并且CD 68+巨噬细胞的数量在衰老肌肉中增加，因此我们测试了巨噬细胞源性TNF-α是否影响肌生成。与野生型巨噬细胞条件培养基相比，TNF-α-null巨噬细胞条件培养基在体外增加了肌细胞融合。此外，将来自野生型小鼠的骨髓细胞移植到TNF-α-null受体中增加了卫星细胞数量并减少了中央有核肌纤维的数量，表明髓样细胞分泌的TNF-α减少了肌细胞融合。将野生型小鼠的骨髓细胞移植到TNF-α-null受体中也会增加肌肉减少症，尽管移植并不能恢复肌纤维表型的年龄相关变化。总的来说，我们表明髓样细胞来源的TNF-α通过影响肌肉减少症和肌细胞与老化肌纤维的融合而促进肌肉老化。我们的研究结果还表明，肌肉固有的TNF-α和免疫细胞分泌的TNF-α共同影响肌肉衰老。
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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影响因子：
64.8
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