Direct contribution of skeletal muscle mesenchymal progenitors to bone repair.
Direct contribution of skeletal muscle mesenchymal progenitors to bone repair.
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骨骼肌间充质祖细胞对骨修复的直接贡献。
DOI：
10.1038/s41467-021-22842-5
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发表时间：
2021-05-17
影响因子：
16.6
通讯作者：
Colnot C
中科院分区：
文献类型：
--
作者：
Julien A;Kanagalingam A;Martínez-Sarrà E;Megret J;Luka M;Ménager M;Relaix F;Colnot C
骨骼通过组织驻留干细胞/祖细胞的激活、纤维愈伤组织的形成以及软骨和骨基质的沉积而再生。在这里，我们表明，间充质祖细胞居住在骨骼肌邻近骨介导的初始纤维化反应，骨损伤，也参与软骨和骨的形成。联合谱系和单细胞RNA测序分析显示，骨骼肌间充质祖细胞在骨折后参与软骨形成之前采用纤维化命运。在多发性创伤中，骨和骨骼肌受损，骨骼肌间充质祖细胞表现出改变的纤维形成和软骨形成。这导致骨愈合受损，这是由于源自骨骼肌的纤维化组织的积累，并且可以通过抗纤维化剂伊马替尼来纠正。这些结果阐明了骨骼肌在骨再生中的核心作用，并提供了骨骼肌可以靶向预防持续性骨痂纤维化和改善肌肉骨骼创伤后骨愈合的证据。骨再生涉及组织驻留干细胞的活化。在这里，作者表明，来自骨骼肌的间充质祖细胞介导了对骨损伤的纤维化反应，也有助于骨修复;当肌肉和骨都受伤时，这些过程都会受损。
Bone regenerates by activation of tissue resident stem/progenitor cells, formation of a fibrous callus followed by deposition of cartilage and bone matrices. Here, we show that mesenchymal progenitors residing in skeletal muscle adjacent to bone mediate the initial fibrotic response to bone injury and also participate in cartilage and bone formation. Combined lineage and single-cell RNA sequencing analyses reveal that skeletal muscle mesenchymal progenitors adopt a fibrogenic fate before they engage in chondrogenesis after fracture. In polytrauma, where bone and skeletal muscle are injured, skeletal muscle mesenchymal progenitors exhibit altered fibrogenesis and chondrogenesis. This leads to impaired bone healing, which is due to accumulation of fibrotic tissue originating from skeletal muscle and can be corrected by the anti-fibrotic agent Imatinib. These results elucidate the central role of skeletal muscle in bone regeneration and provide evidence that skeletal muscle can be targeted to prevent persistent callus fibrosis and improve bone healing after musculoskeletal trauma. Bone regeneration involves activation of tissue resident stem cells. Here the authors show that mesenchymal progenitors from skeletal muscle mediate the fibrotic response to bone injury and also contribute to bone repair; processes that are impaired when both muscle and bone are injured.
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影响因子：
16
作者：
Giordani, Lorenzo;He, Gary J.;Le Grand, Fabien
通讯作者：
Le Grand, Fabien
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
2.8
作者：
Harry, Lorraine E.;Sandison, Ann;Nanchahal, Jagdeep
通讯作者：
Nanchahal, Jagdeep
DOI：
10.1073/pnas.1018501108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Glass, Graeme E.;Chan, James K.;Nanchahal, Jagdeep
通讯作者：
Nanchahal, Jagdeep
影响因子：
4.6
作者：
Hu, Diane P.;Ferro, Federico;Bahney, Chelsea S.
通讯作者：
Bahney, Chelsea S.