Piezo1 balances the osteogenic-tenogenic plasticity of periosteal progenitor cells through the YAP pathway.

IF 7.5 1区 生物学 Q1 CELL BIOLOGY
Lijun Wang, Qian Ren, Shuqin Chen, Lixiang Lou, Xuye Hu, Wenhui Xing, Jinlong Suo, Jun Sun, Matthew B Greenblatt, Heng Feng, Weiguo Zou
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Abstract

The extremity tendons and bones are derived from limb bud mesenchyme, which eventually becomes cells of different tissues. Despite their common origin, it was widely believed that tenocytes and skeletal cells are distinct lineages without interconversion. However, we found that periosteal skeletal progenitor cells could transform between osteogenic and tenogenic commitment. SCX can label the periosteal progenitor cell population. Loss of Piezo1 arrests the periosteal progenitor cells in a progenitor state. Piezo1 deficiency leads to upregulation of Scx expression due to the inhibited YAP nuclear localization. Loss of Piezo1 showed increased tenogenic marker genes and decreased osteogenic marker genes. The periosteal progenitor cells can regenerate the injured tendon more robustly when Piezo1 is absent. Taken together, our data reveal that periosteal SCX+ progenitor cells compromise the osteogenic ability and acquire the tenocyte-biased lineage commitment after loss of Piezo1, providing a strategy to modulate the periosteal progenitor cells for tissue regeneration.

Piezo1通过YAP通路平衡骨膜祖细胞的成骨-肌腱可塑性。
四肢肌腱和骨骼来源于肢芽间充质,最终成为不同组织的细胞。尽管它们有共同的起源,但人们普遍认为腱细胞和骨骼细胞是不同的谱系,没有相互转化。然而,我们发现骨膜骨祖细胞可以在成骨和成骨之间转化。SCX可以标记骨膜祖细胞群。Piezo1的缺失使骨膜祖细胞处于祖细胞状态。Piezo1缺失导致Scx表达上调,这是由于YAP核定位受到抑制。Piezo1缺失表现为骨质标记基因增加,成骨标记基因减少。当Piezo1缺失时,骨膜祖细胞能更强健地再生受损肌腱。综上所述,我们的数据表明,骨膜SCX+祖细胞在失去Piezo1后会损害成骨能力,并获得腱细胞偏向谱系,这为调节骨膜祖细胞进行组织再生提供了一种策略。
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来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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