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骨形态发生蛋白-2信号传导与机械转导协同作用，通过Yes相关蛋白/具有PDZ结合基序的转录共激活因子驱动成骨分化。

BMP-2 Signaling and Mechanotransduction Synergize to Drive Osteogenic Differentiation via YAP/TAZ.

作者信息

Wei Qiang, Holle Andrew, Li Jie, Posa Francesca, Biagioni Francesca, Croci Ottavio, Benk Amelie S, Young Jennifer, Noureddine Fatima, Deng Jie, Zhang Man, Inman Gareth J, Spatz Joachim P, Campaner Stefano, Cavalcanti-Adam Elisabetta A

机构信息

College of Polymer Science and Engineering State Key Laboratory of Polymer Materials and Engineering Sichuan University Chengdu 610065 China.

Department of Cellular Biophysics Max Planck Institute for Medical Research Jahnstraße 29 Heidelberg 69120 Germany.

出版信息

Adv Sci (Weinh). 2020 Jun 16;7(15):1902931. doi: 10.1002/advs.201902931. eCollection 2020 Aug.

DOI:10.1002/advs.201902931
PMID:32775147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7404154/
Abstract

Growth factors and mechanical cues synergistically affect cellular functions, triggering a variety of signaling pathways. The molecular levels of such cooperative interactions are not fully understood. Due to its role in osteogenesis, the growth factor bone morphogenetic protein 2 (BMP-2) is of tremendous interest for bone regenerative medicine, osteoporosis therapeutics, and beyond. Here, contribution of BMP-2 signaling and extracellular mechanical cues to the osteogenic commitment of C2C12 cells is investigated. It is revealed that these two distinct pathways are integrated at the transcriptional level to provide multifactorial control of cell differentiation. The activation of osteogenic genes requires the cooperation of BMP-2 pathway-associated Smad1/5/8 heteromeric complexes and mechanosensitive YAP/TAZ translocation. It is further demonstrated that the Smad complexes remain bound onto and active on target genes, even after BMP-2 removal, suggesting that they act as a "molecular memory unit." Thus, synergistic stimulation with BMP-2 and mechanical cues drives osteogenic differentiation in a programmable fashion.

摘要

生长因子和机械信号协同影响细胞功能，触发多种信号通路。这种协同相互作用的分子水平尚未完全了解。由于其在成骨过程中的作用，生长因子骨形态发生蛋白2（BMP-2）在骨再生医学、骨质疏松症治疗等领域具有极大的研究价值。在此，研究了BMP-2信号和细胞外机械信号对C2C12细胞成骨定向分化的作用。结果表明，这两条不同的信号通路在转录水平整合，以提供对细胞分化的多因素控制。成骨基因的激活需要与BMP-2信号通路相关的Smad1/5/8异源三聚体复合物和机械敏感的YAP/TAZ易位的协同作用。进一步证明，即使在去除BMP-2后，Smad复合物仍能与靶基因结合并保持活性，这表明它们起到了“分子记忆单元”的作用。因此，BMP-2与机械信号的协同刺激以可编程的方式驱动成骨分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/6ebe26b86f29/ADVS-7-1902931-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/d29259235a4a/ADVS-7-1902931-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/1fab39b0452a/ADVS-7-1902931-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/1fbe38a37edb/ADVS-7-1902931-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/53c2231b5747/ADVS-7-1902931-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/6ebe26b86f29/ADVS-7-1902931-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/d29259235a4a/ADVS-7-1902931-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/d0da2e65e073/ADVS-7-1902931-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/1fab39b0452a/ADVS-7-1902931-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/1fbe38a37edb/ADVS-7-1902931-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/53c2231b5747/ADVS-7-1902931-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbe/7404154/6ebe26b86f29/ADVS-7-1902931-g006.jpg

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