Effect of complete abroagation of hyaluronan synthesis on osteogenic differentiation of mesenchymal stem cells (MSc) in vitro
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE271507 | GEO | 2025/07/05
REPOSITORIES: GEO
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Project description:Effect of complete abroagation of hyaluronan synthesis on osteogenic differentiation of mesenchymal stem cells (MSc) in vitro
| PRJNA1132131 | ENA
Project description:Hyaluronan (HA) provides moisturizing benefits and exhibits unique biological activities based on its molecular weight. While the anti-inflammatory effects of high-molecular-weight HA have been well studied, the impact of hyaluronan tetrasaccharide (HA4), an ultralow-molecular-weight HA, on the skin immune system is not fully understood. Thus, we investigated how HA4 affects the differentiation of M1 macrophages, which increase during photoaging. As a result, we added HA4 during the M1 macrophage differentiation phase and conducted a gene expression analysis. HA4 partially decreased the transition from M0 to M1 macrophages and reduced the expression of proinflammatory cytokines like IL-6. However, the M2 marker IL-1ra increased, while IL-10 levels remained constant, suggesting that HA4 does not fully polarize macrophages toward the M2 phenotype. Normal human dermal fibroblasts (NHDF) were treated with an M1 macrophage-conditioned medium (M1-CM) and a modified version containing HA4 (M1+HA4-CM). The M1+HA4-CM notably decreased the expression of IL-6 and IL-8, along with the collagen-degrading enzyme MMP1. Collagen synthesis assays showed that HA4 helped restore collagen fiber formation. Moreover, RNA-seq analysis of NHDF treated with the conditioned medium confirmed that M1+HA4-CM amplified the expression of genes related to collagen production while decreasing collagen-degrading enzyme gene expression. Neutralization assays employing a TLR4 antibody suggested that decreasing IL-6 in NHDF by HA4 may be independent of the TLR4 signaling pathway. HA4 is vital in partially suppressing M1 macrophage differentiation and the release of inflammatory factors, as well as regulating collagen remodeling in NHDF. These findings indicate that HA4 holds promise as a molecule for mitigating inflammation-induced collagen degradation by modulating macrophage activity in photoaged skin.
2025-06-05 | GSE298076 | GEO
Project description:Hyaluronan (HA) provides moisturizing benefits and exhibits unique biological activities based on its molecular weight. While the anti-inflammatory effects of high-molecular-weight HA have been well studied, the impact of hyaluronan tetrasaccharide (HA4), an ultralow-molecular-weight HA, on the skin immune system is not fully understood. Thus, we investigated how HA4 affects the differentiation of M1 macrophages, which increase during photoaging. As a result, we added HA4 during the M1 macrophage differentiation phase and conducted a gene expression analysis. HA4 partially decreased the transition from M0 to M1 macrophages and reduced the expression of proinflammatory cytokines like IL-6. However, the M2 marker IL-1ra increased, while IL-10 levels remained constant, suggesting that HA4 does not fully polarize macrophages toward the M2 phenotype. Normal human dermal fibroblasts (NHDF) were treated with an M1 macrophage-conditioned medium (M1-CM) and a modified version containing HA4 (M1+HA4-CM). The M1+HA4-CM notably decreased the expression of IL-6 and IL-8, along with the collagen-degrading enzyme MMP1. Collagen synthesis assays showed that HA4 helped restore collagen fiber formation. Moreover, RNA-seq analysis of NHDF treated with the conditioned medium confirmed that M1+HA4-CM amplified the expression of genes related to collagen production while decreasing collagen-degrading enzyme gene expression. Neutralization assays employing a TLR4 antibody suggested that decreasing IL-6 in NHDF by HA4 may be independent of the TLR4 signaling pathway. HA4 is vital in partially suppressing M1 macrophage differentiation and the release of inflammatory factors, as well as regulating collagen remodeling in NHDF. These findings indicate that HA4 holds promise as a molecule for mitigating inflammation-induced collagen degradation by modulating macrophage activity in photoaged skin.
2025-06-05 | GSE298073 | GEO
Project description:Efficient osteogenic differentiation of mesenchymal stem cells (MSCs) is crucial to accelerate bone formation. In this context, the use of extracellular matrix (ECM) as natural 3D-framework mimicking in vivo tissue architecture is of interest. The aim of this study was to generate a devitalized human osteogenic MSC-derived ECM and to investigate its impact on MSC osteogenic differentiation to improve MSC properties in bone regeneration. The devitalized ECM significantly enhanced MSC adhesion and proliferation. Osteogenic differentiation and mineralization of MSCs on the ECM was quicker than in standard conditions. The presence of ECM promoted in vivo bone formation by MSCs in a mouse model of ectopic-calcification. We analyzed the ECM composition by mass spectrometry, detecting 846 proteins. Of these, 473 proteins were shared with the human bone proteome we previously described, demonstrating high homology to an in vivo microenvironment. Bioinformatic analysis of the 846 proteins showed involvement in adhesion and osteogenic differentiation, confirming the ECM composition as key modulator of MSC behaviour. In addition to known ECM-components, proteomic analysis revealed novel ECM functions, which could improve culture conditions. In summary, this study provides a simplified method to obtain an in vitro MSC-derived ECM that enhances osteogenic differentiation, and could be applied as natural biomaterial to accelerate bone regeneration.
2022-02-24 | PXD006865 | Pride
Project description:Heterotopic ossification (HO), usually following traumatic challenges, is initiated by the aberrant osteochondral differentiation of mesenchymal stem cell (MSC). However, the role of trauma-induced inflammatory exposure in MSC fate determination remains unclear. Here, we found that quiescent MSC transited into cycling MSC and later gave rise to chondrogenic (cMSC) and/or osteogenic (oMSC) commitment following either muscle or tendon injury via single-cell RNA sequencing and lineage tracing analysis. Further spatial transcriptome analysis revealed that cycling MSC, cMSC and oMSC resided in the inflammatory niche comprised of monocytes/macrophages, neutrophils, dendritic cells (DCs), NK cells, T and B lymphocytes. We uncovered the diversity of each type of immune cells during MSC development and demonstrated that macrophages, including M1 and M2 subtypes, dynamically promotes proliferation and osteochondral differentiation of MSCs. Additionally, neutrophils and NK cells are essential for cycling MSC transition from quiescent MSC. CD4+ and CD8+ T lymphocytes promotes chondrogenesis. CellchatDB analysis and regulon analysis identify several gene networks, which could be essential for aberrant MSC proliferation and osteochondral differentiation respectively. Collectively, our findings indicate that inflammation is necessary to regulate MSC fate and uncovered the molecular landscape of osteoimmunological interactions that occur during aberrant osteochondral differentiation that could be useful for HO treatment.
2025-03-06 | GSE246448 | GEO
Project description:Heterotopic ossification (HO), usually following traumatic challenges, is initiated by the aberrant osteochondral differentiation of mesenchymal stem cell (MSC). However, the role of trauma-induced inflammatory exposure in MSC fate determination remains unclear. Here, we found that quiescent MSC transited into cycling MSC and later gave rise to chondrogenic (cMSC) and/or osteogenic (oMSC) commitment following either muscle or tendon injury via single-cell RNA sequencing and lineage tracing analysis. Further spatial transcriptome analysis revealed that cycling MSC, cMSC and oMSC resided in the inflammatory niche comprised of monocytes/macrophages, neutrophils, dendritic cells (DCs), NK cells, T and B lymphocytes. We uncovered the diversity of each type of immune cells during MSC development and demonstrated that macrophages, including M1 and M2 subtypes, dynamically promotes proliferation and osteochondral differentiation of MSCs. Additionally, neutrophils and NK cells are essential for cycling MSC transition from quiescent MSC. CD4+ and CD8+ T lymphocytes promotes chondrogenesis. CellchatDB analysis and regulon analysis identify several gene networks, which could be essential for aberrant MSC proliferation and osteochondral differentiation respectively. Collectively, our findings indicate that inflammation is necessary to regulate MSC fate and uncovered the molecular landscape of osteoimmunological interactions that occur during aberrant osteochondral differentiation that could be useful for HO treatment.
2025-03-06 | GSE246445 | GEO
Project description:Hyaluronan (HA) is a major component of the skin that exerts a variety of biological functions. Inter-α-trypsin inhibitor heavy chain (ITIH) proteins comprise a family of hyaladherins of which ITIH5 was recently described in skin, playing a functional role in skin morphology and inflammatory skin diseases including allergic contact dermatitis (ACD). The current study focused on the ITIH5-HA interaction and its potential clinical and functional impact in extracellular matrix (ECM) stabilization. Using murine skin models, ITIH5 knockdown fibroblasts and a reactive oxygen species (ROS)-mediated HA degradation assay we proved that ITIH5 binds to HA thereby acting as a stabilizer of HA. Moreover, micro-array profiling revealed the impact of ITIH5 on biological processes such as skin development and ECM homeostasis. To understand more precisely the role of ITIH5 in inflammatory skin diseases such as ACD we generated ITIH5 knockout cells of the KeratinoSens cell line. Performing the in vitro KeratinoSens skin sensitization assay, we detected that ITIH5 decreases the sensitizing potential of moderate and strong contact sensitizers. Taken together, our experiments revealed that ITIH5 forms complexes with HA, thereby on the one hand stabilizing HA and facilitating the formation of ECM structures and on the other hand modulating inflammatory responses.
2019-12-05 | GSE141495 | GEO
Project description:Abundant high molecular weight hyaluronic acid (HMW-HA) contributes to cancer resistance and possibly longevity of the longest-lived rodent, the naked mole-rat1,2. To study whether the benefits of increased HMW-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHAS2). nmrHAS2 mice showed increase in hyaluronan levels in several tissues, and lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHAS2 mice shifted towards that of longer-lived species. The most striking change observed in nmrHAS2 mice was attenuated inflammation across multiple tissues. HMW-HA reduced inflammation via several pathways including direct immunoregulatory effect on immune cells, protection from oxidative stress, and improved gut barrier function during aging. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exploited to other species, and open new avenues for using HMW-HA to improve lifespan and healthspan
2023-09-08 | GSE234154 | GEO
Project description:Abundant high molecular weight hyaluronic acid (HMW-HA) contributes to cancer resistance and possibly longevity of the longest-lived rodent, the naked mole-rat1,2. To study whether the benefits of increased HMW-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHAS2). nmrHAS2 mice showed increase in hyaluronan levels in several tissues, and lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHAS2 mice shifted towards that of longer-lived species. The most striking change observed in nmrHAS2 mice was attenuated inflammation across multiple tissues. HMW-HA reduced inflammation via several pathways including direct immunoregulatory effect on immune cells, protection from oxidative stress, and improved gut barrier function during aging. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exploited to other species, and open new avenues for using HMW-HA to improve lifespan and healthspan.
2023-08-10 | GSE234563 | GEO
Project description:Investigation of the role of hyaluronan in cardiomyocytes . The aims of the study were to determine if cardiomyocytes are capable of detecting hyaluronan and if then intrecellular signaling causes changes in gene expression. The study showed that cardiomyocytes can bind hyaluronan with following change in gene expression.
2011-11-01 | GSE21675 | GEO