Modulation of ossification and inflammatory pathways during dexamethasone-induced in vitro osteogenesis
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Le résumé fourni par la source
Abstract Background Dexamethasone (DEX) is used in vitro to promote osteogenic differentiation of human bone marrow mesenchymal stromal cells (hBMSCs). In clinical use, however, glucocorticoids induce osteoblast and osteocyte apoptosis while increasing osteoclast survival, leading overall to osteoporosis and high fracture risk. The overall impact of DEX on the differentiation of human progenitor cells remains contradictory and not fully understood, highlighting the need for further investigation using sequencing approaches as in vitro results will naturally influence further translational research. Methods hBMSCs were induced to osteogenic differentiation for 7 days using different concentrations of either DEX or the nonsteroidal glucocorticoid receptor agonist (+)-ZK216348. cDNA library preparation and RNA sequencing (RNAseq) were performed using Oxford Nanopore Technologies. Differentially expressed genes and pathways associated to the transactivation or transrepression activity of DEX were identified. Sequencing results were validated by qPCR, protein analysis, and with a functional assay on peripheral blood mononuclear cells to determine the overall effect of the BMSC supernatant. Results Hierarchical clustering of RNAseq data identified eight subclusters with shared regulatory patterns. Enrichment analysis revealed that both upregulated and downregulated genes are involved in ossification and extracellular matrix organization pathways. Several pro- and anti-inflammatory genes were differentially regulated. qPCR analysis validated the upregulation of CXCL1 , CXCL8 , IL18 , and COL8A1 , while MMP1 and CXCL12 expression decreased in response to DEX. Comparing DEX results with those obtained using (+)-ZK216348 helped distinguish the potential mechanisms regulating the expression of specific genes. Notably, CXCL8 upregulation occurred through transactivation, whereas COL8A1 upregulation is downstream of a transrepressed gene. Further in vitro experiments confirmed that DEX significantly increased CXCL8 expression and IL-8 secretion. However, hPBMC responses indicated no significant pro- or anti-inflammatory effects from hBMSC conditioned medium. Conclusions In conclusion, the effects of DEX on the transcriptome of hBMSCs in a pro-osteogenic environment do not fully replicate the acquisition of an osteogenic phenotype. Several genes associated with ossification, extracellular matrix organization, and inflammation were dysregulated. The unique expression patterns of pro-inflammatory cytokines and collagen types warrant further investigation to elucidate their roles in osteogenic differentiation and bone homeostasis.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Modulation of ossification and inflammatory pathways during dexamethasone-induced <i>in vitro</i> osteogenesis
- Date Crossref
- 13/02/2026
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Applied Sciences and Arts of Southern Switzerland pays non établi dans la noticeUniversité ou école supérieure
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AO Foundation pays non établi dans la noticeOrganisation à but non lucratif
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University of Basel Department of Biomedical Engineering pays non établi dans la noticeUniversité ou école supérieure
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University of Ferrara Department of Medical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Dalle Molle Institute for Artificial Intelligence Research pays non établi dans la noticeStructure de recherche
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University of Bern Graduate School for Health Sciences pays non établi dans la noticeUniversité ou école supérieure
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University Hospital of Bern pays non établi dans la noticeÉtablissement de santé
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University of Applied Sciences of Southern Switzerland (SUPSI) Laboratory of applied microbiology (LMA) pays non établi dans la noticeUniversité ou école supérieure
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AO Research Institute Davos pays non établi dans la noticeStructure de recherche
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Bern University Hospital Department of Orthopaedic Surgery and Traumatology pays non établi dans la noticeUniversité ou école supérieure
University of Applied Sciences and Arts of Southern Switzerland, AO Foundation et Department of Biomedical Engineering — University of Basel, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.