{"title":"间充质干细胞与不同糖皮质激素剂量的联合应用可减轻系统性红斑狼疮小鼠模型的骨质疏松症。","authors":"Sisi Ding, Tian Ren, Saizhe Song, Cheng Peng, Cuiping Liu, Jian Wu, Xin Chang","doi":"10.1002/iid3.1319","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>Bone mesenchymal stem cells (BMSCs) have been tentatively applied in the treatment of glucocorticoid-induced osteoporosis (GIOP) and systemic lupus erythematosus (SLE). However, the effects of BMSCs on osteoporosis within the context of glucocorticoid (GC) application in SLE remain unclear. Our aim was to explore the roles of BMSCs and different doses of GC interventions on osteoporosis in SLE murine models.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>MRL/MpJ-Faslpr mice were divided into eight groups with BMSC treatment and different dose of GC intervention. Three-dimensional imaging analysis and hematoxylin and eosin (H&E) staining were performed to observe morphological changes. The concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in serum were measured by enzyme-linked immunosorbent assay (ELISA). The subpopulation of B cells and T cells in bone marrows and spleens were analyzed by flow cytometry. Serum cytokines and chemokines were assessed using Luminex magnetic bead technology.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>BMSCs ameliorated osteoporosis in murine SLE models by enhancing bone mass, improving bone structure, and promoting bone formation through increased bone mineral content and optimization of trabecular morphology. BMSC and GC treatments reduced the number of B cells in bone marrows, but the effect was not significant in spleens. BMSCs significantly promoted the expression of IL-10 while reducing IL-18. Moreover, BMSCs exert immunomodulatory effects by reducing Th17 expression and rectifying the Th17/Treg imbalance.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>BMSCs effectively alleviate osteoporosis induced by SLE itself, as well as osteoporosis resulting from SLE combined with various doses of GC therapy. The therapeutic effects of BMSCs appear to be mediated by their influence on bone marrow B cells, T cell subsets, and associated cytokines. High-dose GC treatment exerts a potent anti-inflammatory effect but may hinder the immunotherapeutic potential of BMSCs. Our research may offer valuable guidance to clinicians regarding the use of BMSC treatment in SLE and provide insights into the judicious use of GCs in clinical practice.</p>\n </section>\n </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.1319","citationCount":"0","resultStr":"{\"title\":\"Combined application of mesenchymal stem cells and different glucocorticoid dosing alleviates osteoporosis in SLE murine models\",\"authors\":\"Sisi Ding, Tian Ren, Saizhe Song, Cheng Peng, Cuiping Liu, Jian Wu, Xin Chang\",\"doi\":\"10.1002/iid3.1319\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>Bone mesenchymal stem cells (BMSCs) have been tentatively applied in the treatment of glucocorticoid-induced osteoporosis (GIOP) and systemic lupus erythematosus (SLE). However, the effects of BMSCs on osteoporosis within the context of glucocorticoid (GC) application in SLE remain unclear. Our aim was to explore the roles of BMSCs and different doses of GC interventions on osteoporosis in SLE murine models.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>MRL/MpJ-Faslpr mice were divided into eight groups with BMSC treatment and different dose of GC intervention. Three-dimensional imaging analysis and hematoxylin and eosin (H&E) staining were performed to observe morphological changes. The concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in serum were measured by enzyme-linked immunosorbent assay (ELISA). The subpopulation of B cells and T cells in bone marrows and spleens were analyzed by flow cytometry. Serum cytokines and chemokines were assessed using Luminex magnetic bead technology.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>BMSCs ameliorated osteoporosis in murine SLE models by enhancing bone mass, improving bone structure, and promoting bone formation through increased bone mineral content and optimization of trabecular morphology. BMSC and GC treatments reduced the number of B cells in bone marrows, but the effect was not significant in spleens. BMSCs significantly promoted the expression of IL-10 while reducing IL-18. Moreover, BMSCs exert immunomodulatory effects by reducing Th17 expression and rectifying the Th17/Treg imbalance.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>BMSCs effectively alleviate osteoporosis induced by SLE itself, as well as osteoporosis resulting from SLE combined with various doses of GC therapy. The therapeutic effects of BMSCs appear to be mediated by their influence on bone marrow B cells, T cell subsets, and associated cytokines. High-dose GC treatment exerts a potent anti-inflammatory effect but may hinder the immunotherapeutic potential of BMSCs. Our research may offer valuable guidance to clinicians regarding the use of BMSC treatment in SLE and provide insights into the judicious use of GCs in clinical practice.</p>\\n </section>\\n </div>\",\"PeriodicalId\":13289,\"journal\":{\"name\":\"Immunity, Inflammation and Disease\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-06-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.1319\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunity, Inflammation and Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/iid3.1319\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunity, Inflammation and Disease","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/iid3.1319","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Combined application of mesenchymal stem cells and different glucocorticoid dosing alleviates osteoporosis in SLE murine models
Objective
Bone mesenchymal stem cells (BMSCs) have been tentatively applied in the treatment of glucocorticoid-induced osteoporosis (GIOP) and systemic lupus erythematosus (SLE). However, the effects of BMSCs on osteoporosis within the context of glucocorticoid (GC) application in SLE remain unclear. Our aim was to explore the roles of BMSCs and different doses of GC interventions on osteoporosis in SLE murine models.
Methods
MRL/MpJ-Faslpr mice were divided into eight groups with BMSC treatment and different dose of GC intervention. Three-dimensional imaging analysis and hematoxylin and eosin (H&E) staining were performed to observe morphological changes. The concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in serum were measured by enzyme-linked immunosorbent assay (ELISA). The subpopulation of B cells and T cells in bone marrows and spleens were analyzed by flow cytometry. Serum cytokines and chemokines were assessed using Luminex magnetic bead technology.
Results
BMSCs ameliorated osteoporosis in murine SLE models by enhancing bone mass, improving bone structure, and promoting bone formation through increased bone mineral content and optimization of trabecular morphology. BMSC and GC treatments reduced the number of B cells in bone marrows, but the effect was not significant in spleens. BMSCs significantly promoted the expression of IL-10 while reducing IL-18. Moreover, BMSCs exert immunomodulatory effects by reducing Th17 expression and rectifying the Th17/Treg imbalance.
Conclusion
BMSCs effectively alleviate osteoporosis induced by SLE itself, as well as osteoporosis resulting from SLE combined with various doses of GC therapy. The therapeutic effects of BMSCs appear to be mediated by their influence on bone marrow B cells, T cell subsets, and associated cytokines. High-dose GC treatment exerts a potent anti-inflammatory effect but may hinder the immunotherapeutic potential of BMSCs. Our research may offer valuable guidance to clinicians regarding the use of BMSC treatment in SLE and provide insights into the judicious use of GCs in clinical practice.
期刊介绍:
Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including:
• cellular and molecular immunology
• clinical immunology
• allergy
• immunochemistry
• immunogenetics
• immune signalling
• immune development
• imaging
• mathematical modelling
• autoimmunity
• transplantation immunology
• cancer immunology