{"title":"PKCβ表达参与M1巨噬细胞诱导的牙周韧带干细胞成骨分化损伤。","authors":"Yang Liu, Zhaocen Liu","doi":"10.1007/s11626-025-01032-3","DOIUrl":null,"url":null,"abstract":"<p><p>Protein kinase Cβ (PRKCB) is expressed in THP-1 cells and has been found upregulated in periodontitis. Exploring the specific molecular mechanisms that promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is beneficial to optimizing periodontal regeneration. THP-1 cells were induced to differentiate into macrophages, and the levels of PRKCB in macrophages with different phenotypes were examined, including PKC activity. The effect of pg-LPS induction on osteogenic differentiation of hPDLSCs was measured by measuring alkaline phosphatase, osteocalcin, osteogenic-related proteins, and mineralized nodules. Ruboxistaurin, an inhibitor of PRKCB, was used to treat M1 macrophages to examine its effect on macrophage polarization. Additionally, the cascade effect of ruboxistaurin on osteogenic differentiation was investigated by co-incubating hPDLSCs with medium from macrophages. The results indicated that PRKCB upregulation and increased PKC activity were induced in M1 macrophages upon stimulation with LPS/IFN-γ. pg-LPS resulted in decreased levels of osteogenic-related genes in hPDLSCs, accompanied by a decrease in mineralized nodules. PRKCB inhibitor reduced PKC activity, inhibited macrophage M1 polarization, and reduced M1-related inflammatory cytokine secretion. Exposure of hPDLSCs to M1 macrophage-derived conditioned medium impaired their osteogenic differentiation potentials, which was significantly attenuated by pretreatment of M1 macrophages with ruboxistaurin. Together, inhibition of PRKCB suppressed inflammatory M1 macrophage polarization, thus attenuating M1 macrophage-induced impairment in the osteogenic differentiation of hPDLSCs. These results provide a theoretical and scientific basis for optimizing the potential clinical application of hPDLSC therapy in periodontal regeneration.</p>","PeriodicalId":13340,"journal":{"name":"In Vitro Cellular & Developmental Biology. Animal","volume":" ","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PKCβ expression contributes to M1 macrophage-induced impairment in the osteogenic differentiation of periodontal ligament stem cells.\",\"authors\":\"Yang Liu, Zhaocen Liu\",\"doi\":\"10.1007/s11626-025-01032-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Protein kinase Cβ (PRKCB) is expressed in THP-1 cells and has been found upregulated in periodontitis. Exploring the specific molecular mechanisms that promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is beneficial to optimizing periodontal regeneration. THP-1 cells were induced to differentiate into macrophages, and the levels of PRKCB in macrophages with different phenotypes were examined, including PKC activity. The effect of pg-LPS induction on osteogenic differentiation of hPDLSCs was measured by measuring alkaline phosphatase, osteocalcin, osteogenic-related proteins, and mineralized nodules. Ruboxistaurin, an inhibitor of PRKCB, was used to treat M1 macrophages to examine its effect on macrophage polarization. Additionally, the cascade effect of ruboxistaurin on osteogenic differentiation was investigated by co-incubating hPDLSCs with medium from macrophages. The results indicated that PRKCB upregulation and increased PKC activity were induced in M1 macrophages upon stimulation with LPS/IFN-γ. pg-LPS resulted in decreased levels of osteogenic-related genes in hPDLSCs, accompanied by a decrease in mineralized nodules. PRKCB inhibitor reduced PKC activity, inhibited macrophage M1 polarization, and reduced M1-related inflammatory cytokine secretion. Exposure of hPDLSCs to M1 macrophage-derived conditioned medium impaired their osteogenic differentiation potentials, which was significantly attenuated by pretreatment of M1 macrophages with ruboxistaurin. Together, inhibition of PRKCB suppressed inflammatory M1 macrophage polarization, thus attenuating M1 macrophage-induced impairment in the osteogenic differentiation of hPDLSCs. These results provide a theoretical and scientific basis for optimizing the potential clinical application of hPDLSC therapy in periodontal regeneration.</p>\",\"PeriodicalId\":13340,\"journal\":{\"name\":\"In Vitro Cellular & Developmental Biology. Animal\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2025-06-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"In Vitro Cellular & Developmental Biology. Animal\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s11626-025-01032-3\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"In Vitro Cellular & Developmental Biology. Animal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11626-025-01032-3","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
PKCβ expression contributes to M1 macrophage-induced impairment in the osteogenic differentiation of periodontal ligament stem cells.
Protein kinase Cβ (PRKCB) is expressed in THP-1 cells and has been found upregulated in periodontitis. Exploring the specific molecular mechanisms that promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is beneficial to optimizing periodontal regeneration. THP-1 cells were induced to differentiate into macrophages, and the levels of PRKCB in macrophages with different phenotypes were examined, including PKC activity. The effect of pg-LPS induction on osteogenic differentiation of hPDLSCs was measured by measuring alkaline phosphatase, osteocalcin, osteogenic-related proteins, and mineralized nodules. Ruboxistaurin, an inhibitor of PRKCB, was used to treat M1 macrophages to examine its effect on macrophage polarization. Additionally, the cascade effect of ruboxistaurin on osteogenic differentiation was investigated by co-incubating hPDLSCs with medium from macrophages. The results indicated that PRKCB upregulation and increased PKC activity were induced in M1 macrophages upon stimulation with LPS/IFN-γ. pg-LPS resulted in decreased levels of osteogenic-related genes in hPDLSCs, accompanied by a decrease in mineralized nodules. PRKCB inhibitor reduced PKC activity, inhibited macrophage M1 polarization, and reduced M1-related inflammatory cytokine secretion. Exposure of hPDLSCs to M1 macrophage-derived conditioned medium impaired their osteogenic differentiation potentials, which was significantly attenuated by pretreatment of M1 macrophages with ruboxistaurin. Together, inhibition of PRKCB suppressed inflammatory M1 macrophage polarization, thus attenuating M1 macrophage-induced impairment in the osteogenic differentiation of hPDLSCs. These results provide a theoretical and scientific basis for optimizing the potential clinical application of hPDLSC therapy in periodontal regeneration.
期刊介绍:
In Vitro Cellular & Developmental Biology - Animal is a journal of the Society for In Vitro Biology (SIVB). Original manuscripts reporting results of research in cellular, molecular, and developmental biology that employ or are relevant to organs, tissue, tumors, and cells in vitro will be considered for publication. Topics covered include:
Biotechnology;
Cell and Tissue Models;
Cell Growth/Differentiation/Apoptosis;
Cellular Pathology/Virology;
Cytokines/Growth Factors/Adhesion Factors;
Establishment of Cell Lines;
Signal Transduction;
Stem Cells;
Toxicology/Chemical Carcinogenesis;
Product Applications.