Rong-Shen Yang , Shuan-Ji Ou , Wei Zeng , Yu-Dun Qu , Jia-Xuan Li , Jiang-Ping Wen , Jia-Bao Liu , Chang-Liang Xia , Yong Qi , Chang-Peng Xu
{"title":"在骨感染中,Piezo1促进M1巨噬细胞极化并损害成骨分化。","authors":"Rong-Shen Yang , Shuan-Ji Ou , Wei Zeng , Yu-Dun Qu , Jia-Xuan Li , Jiang-Ping Wen , Jia-Bao Liu , Chang-Liang Xia , Yong Qi , Chang-Peng Xu","doi":"10.1016/j.bbadis.2025.168042","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Bone infection induces a strong inflammatory response and leads to impaired bone regeneration, in which macrophages sense mechanistic signals and modulate immune responses in the inflammatory microenvironment through Piezo1. Nonetheless, the regulatory role of Piezo1 in macrophages during bone infection remains elusive.</div></div><div><h3>Methods</h3><div>Rat models of infected bone defects were established for bulk RNA sequencing and single-cell RNA sequencing. Tissues were collected from infected human bones and infected bone marrow cavity tissues of rats for in vivo validation. Indirect co-culture cell experiments were conducted using mouse mononuclear macrophages and mouse bone marrow mesenchymal stem cells for <em>in virto</em> validation.</div></div><div><h3>Results</h3><div>Piezo1 was upregulated in bone marrow macrophages during infection, driving M1 polarization and inflammatory cytokine secretion, which triggered PANoptosis and impaired the osteogenic differentiation of bone marrow mesenchymal stem cells. Piezo1 inhibition attenuated these effects, confirming its regulatory role.</div></div><div><h3>Conclusions</h3><div>Within the inflammatory microenvironment during infection, Piezo1 expression is increased in macrophages and mediates macrophage polarization toward M1 and pro-inflammatory cytokine secretion, inducing PANoptosis and impairing osteogenic differentiation in bone marrow mesenchymal stem cells. Targeting Piezo1-mediated crosstalk between macrophages and bone marrow mesenchymal stem cells offers a novel strategy for restoring bone regeneration in bone infection.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 1","pages":"Article 168042"},"PeriodicalIF":4.2000,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Piezo1 promotes M1 macrophage polarization and impairs osteogenic differentiation in bone infection\",\"authors\":\"Rong-Shen Yang , Shuan-Ji Ou , Wei Zeng , Yu-Dun Qu , Jia-Xuan Li , Jiang-Ping Wen , Jia-Bao Liu , Chang-Liang Xia , Yong Qi , Chang-Peng Xu\",\"doi\":\"10.1016/j.bbadis.2025.168042\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Bone infection induces a strong inflammatory response and leads to impaired bone regeneration, in which macrophages sense mechanistic signals and modulate immune responses in the inflammatory microenvironment through Piezo1. Nonetheless, the regulatory role of Piezo1 in macrophages during bone infection remains elusive.</div></div><div><h3>Methods</h3><div>Rat models of infected bone defects were established for bulk RNA sequencing and single-cell RNA sequencing. Tissues were collected from infected human bones and infected bone marrow cavity tissues of rats for in vivo validation. Indirect co-culture cell experiments were conducted using mouse mononuclear macrophages and mouse bone marrow mesenchymal stem cells for <em>in virto</em> validation.</div></div><div><h3>Results</h3><div>Piezo1 was upregulated in bone marrow macrophages during infection, driving M1 polarization and inflammatory cytokine secretion, which triggered PANoptosis and impaired the osteogenic differentiation of bone marrow mesenchymal stem cells. Piezo1 inhibition attenuated these effects, confirming its regulatory role.</div></div><div><h3>Conclusions</h3><div>Within the inflammatory microenvironment during infection, Piezo1 expression is increased in macrophages and mediates macrophage polarization toward M1 and pro-inflammatory cytokine secretion, inducing PANoptosis and impairing osteogenic differentiation in bone marrow mesenchymal stem cells. Targeting Piezo1-mediated crosstalk between macrophages and bone marrow mesenchymal stem cells offers a novel strategy for restoring bone regeneration in bone infection.</div></div>\",\"PeriodicalId\":8821,\"journal\":{\"name\":\"Biochimica et biophysica acta. 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Piezo1 promotes M1 macrophage polarization and impairs osteogenic differentiation in bone infection
Background
Bone infection induces a strong inflammatory response and leads to impaired bone regeneration, in which macrophages sense mechanistic signals and modulate immune responses in the inflammatory microenvironment through Piezo1. Nonetheless, the regulatory role of Piezo1 in macrophages during bone infection remains elusive.
Methods
Rat models of infected bone defects were established for bulk RNA sequencing and single-cell RNA sequencing. Tissues were collected from infected human bones and infected bone marrow cavity tissues of rats for in vivo validation. Indirect co-culture cell experiments were conducted using mouse mononuclear macrophages and mouse bone marrow mesenchymal stem cells for in virto validation.
Results
Piezo1 was upregulated in bone marrow macrophages during infection, driving M1 polarization and inflammatory cytokine secretion, which triggered PANoptosis and impaired the osteogenic differentiation of bone marrow mesenchymal stem cells. Piezo1 inhibition attenuated these effects, confirming its regulatory role.
Conclusions
Within the inflammatory microenvironment during infection, Piezo1 expression is increased in macrophages and mediates macrophage polarization toward M1 and pro-inflammatory cytokine secretion, inducing PANoptosis and impairing osteogenic differentiation in bone marrow mesenchymal stem cells. Targeting Piezo1-mediated crosstalk between macrophages and bone marrow mesenchymal stem cells offers a novel strategy for restoring bone regeneration in bone infection.
期刊介绍:
BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.