Skeletal Stem/Progenitor Cells in Periosteum and Skeletal Muscle Share a Common Molecular Response to Bone Injury.
Skeletal Stem/Progenitor Cells in Periosteum and Skeletal Muscle Share a Common Molecular Response to Bone Injury.
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DOI：
10.1002/jbmr.4616
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发表时间：
2022-08
影响因子：
6.2
通讯作者：
Colnot, Celine
中科院分区：
文献类型：
--
作者：
Julien, Anais;Perrin, Simon;Martinez-Sarra, Ester;Kanagalingam, Anuya;Carvalho, Caroline;Luka, Marine;Menager, Mickael;Colnot, Celine
骨再生涉及从骨髓、骨膜和邻近骨骼肌中募集的骨干/祖细胞（SSPCs）。为了实现损伤后的骨重建，这些细胞群需要协调的细胞和分子反应。在这里，我们发现来自骨膜和骨骼肌的SSPCs富含骨软骨祖细胞，与骨髓基质细胞相比，它们在骨折修复过程中更有效地促进软骨内成骨。骨膜细胞的单细胞RNA测序（RNAseq）分析揭示了骨膜在稳定状态和骨折时的细胞异质性。骨折后，骨膜和骨骼肌SSPCs在软骨形成之前从干/祖细胞转变为纤维细胞状态。骨膜和骨骼肌SSPCs的这种常见激活模式是由骨形态发生蛋白（BMP）信号介导的。功能上，Bmpr1a基因失活在血小板衍生的生长因子受体α (Pdgfra)衍生的SSPC中会损害骨愈合，并减少SSPC的增殖、迁移和骨软骨分化。这些结果揭示了一个协调的分子程序，驱动骨膜和骨骼肌中SSPC的激活，以促进骨再生过程中的软骨内成骨。©2022作者。由Wiley期刊有限责任公司代表美国骨与矿物研究协会（ASBMR）出版的骨与矿物研究杂志。
Bone regeneration involves skeletal stem/progenitor cells (SSPCs) recruited from bone marrow, periosteum, and adjacent skeletal muscle. To achieve bone reconstitution after injury, a coordinated cellular and molecular response is required from these cell populations. Here, we show that SSPCs from periosteum and skeletal muscle are enriched in osteochondral progenitors, and more efficiently contribute to endochondral ossification during fracture repair as compared to bone‐marrow stromal cells. Single‐cell RNA sequencing (RNAseq) analyses of periosteal cells reveal the cellular heterogeneity of periosteum at steady state and in response to bone fracture. Upon fracture, both periosteal and skeletal muscle SSPCs transition from a stem/progenitor to a fibrogenic state prior to chondrogenesis. This common activation pattern in periosteum and skeletal muscle SSPCs is mediated by bone morphogenetic protein (BMP) signaling. Functionally, Bmpr1a gene inactivation in platelet‐derived growth factor receptor alpha (Pdgfra)‐derived SSPCs impairs bone healing and decreases SSPC proliferation, migration, and osteochondral differentiation. These results uncover a coordinated molecular program driving SSPC activation in periosteum and skeletal muscle toward endochondral ossification during bone regeneration. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
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：
5.2
作者：
Grcevic, Danka;Pejda, Slavica;Matthews, Brya G.;Repic, Dario;Wang, Liping;Li, Haitao;Kronenberg, Mark S.;Jiang, Xi;Maye, Peter;Adams, Douglas J.;Rowe, David W.;Aguila, Hector L.;Kalajzic, Ivo
通讯作者：
Kalajzic, Ivo
影响因子：
4.1
作者：
Ferretti, Concetta;Mattioli-Belmonte, Monica
通讯作者：
Mattioli-Belmonte, Monica