The Lachnospiraceae-butyric acid axis and its role in glucocorticoid-associated osteonecrosis DOI Creative Commons

Mingbin Guo,

Shuai He, Wei Song

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 11, 2024

Glucocorticoids (GCs) are key inducers of osteonecrosis, yet not all patients treated with GCs develop glucocorticoid-associated osteonecrosis (GAON). The factors mediating this relationship unclear. Studies have shown that gut microbiota and their metabolites influence bone metabolism, but role in GAON is This study aimed to explore the connection between microbiota. Through bidirectional Mendelian randomization analysis, we identified 14 microbial taxa, including Lachnospiraceae (IVW, P = 0.011), associated GAON. RNA-seq analysis revealed differentially expressed genes (DEGs) were enriched for intestinal inflammatory response mechanisms. We then compared who developed (17 cases), those did (GAnON, 15 untreated (Blank, cases) composition, short-chain fatty acids (SCFAs), serum factors. Our findings indicated a decrease abundance (GAON 17.13%, GAnON 12.51%, Blank 24.52%) GC-treated patients. Serum (IL-17 A, IL-33, TNF-α) (59.603 ± 12.147, 89.337 20.714, 42.584 9.185) showed significant differences (1.446 0.683, 11.534 4.705, 4.682 1.48) (25.353 8.181, 32.527 7.352, 12.49 3.217) groups, negative correlation these levels. Butyric acid levels SCFAs varied among groups (P<0.01) correlated Controlled experiments rats demonstrated butyric acid's osteoprotective development (P<0.01). In conclusion, our suggests reduced levels, along increased inflammation due use, contribute may mediate effects inflammation. Butyrate supplementation could potentially reduce incidence, offering novel approach its clinical management.

Language: Английский

Precisely Regulating M2 Subtype Macrophages for Renal Fibrosis Resolution DOI
Lihua Luo, Sijie Wang, Yilong Hu

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(22), P. 22508 - 22526

Published: Nov. 10, 2023

Macrophages are central to the pathogenesis of kidney disease and serve as an effective therapeutic target for injury fibrosis. Among them, M2-type macrophages have double-edged effects regarding anti-inflammatory tissue repair. Depending on polarization M2 subtypes (M2a or M2c) in diseased microenvironment, they can either mediate normal repair drive In renal fibrosis, M2a promotes progression through macrophage-to-myofibroblast transition (MMT) cells, while M2c possesses potent functions repair, is inhibited. The mechanisms underlying this differentiation complex currently not well understood. Therefore, study, we first confirmed that M2a-derived MMT cells responsible development fibrosis demonstrated intensity TGF-β signaling a major factor determining differential M2c. Under excessive stimulation, undergoes process known whereas moderate stimulation favors phenotype macrophages. Based these findings, employed targeted nanotechnology codeliver endoplasmic reticulum stress (ERS) inhibitor (Ceapin 7, Cea C) conventional glucocorticoids (Dexamethasone, Dex D), precisely modulating ATF6/TGF-β/Smad3 axis within This approach calibrated level macrophages, promoting their toward suppressing polarization. study indicates combination ERS first-line drug holds promise resolution.

Language: Английский

Citations

29
MiR-370-3p regulate TLR4/SLC7A11/GPX4 to alleviate the progression of glucocorticoids-induced osteonecrosis of the femoral head by promoting osteogenesis and suppressing ferroptosis DOI Creative Commons

Rongtai Zuo,

Bojun Cao, Lingchi Kong

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
Targeting different phenotypes of macrophages: A potential strategy for natural products to treat inflammatory bone and joint diseases DOI
Yuhe Gao, Xilin Xu, Xiaofeng Zhang

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 118, P. 154952 - 154952

Published: July 12, 2023

Language: Английский

Citations

18
Construction of oxidized icariin functionalized collagen composite with promoting osteogenesis, vascularization and anti-inflammatory properties potential for bone repair application DOI

Fufen Li,

Min Gong,

Yining Chen

et al.

European Polymer Journal, Journal Year: 2024, Volume and Issue: 205, P. 112755 - 112755

Published: Jan. 9, 2024

Language: Английский

Citations

7
Potential mechanisms of rheumatoid arthritis therapy: Focus on macrophage polarization DOI

Xinyu Yang,

Jinling Li, Chengchao Xu

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113058 - 113058

Published: Sept. 4, 2024

Language: Английский

Citations

5
Early depletion of M1 macrophages retards the progression of glucocorticoid-associated osteonecrosis of the femoral head DOI Creative Commons
Yannan Cheng, Hui Chen, Ping Duan

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 122, P. 110639 - 110639

Published: July 21, 2023

Inflammation stands as a pivotal factor in the pathogenesis of glucocorticoid-associated osteonecrosis femoral head (GA-ONFH). However, vital role played by M1 macrophages, principal constituents inflammatory process, remains largely underexplored. In this study, we employed reverse transcription-quantitative polymerase chain Reaction (RT-PCR), western blot, and flow cytometry to assess impact M1-conditioned medium on cultures mouse bone marrow-derived mesenchymal stem cells (BMSCs) Murine Long Osteocyte-Y4 (MLO-Y4) vitro. Moreover, quantified levels cytokines through employment an enzyme-linked immunosorbent assay (ELISA). For vivo analysis, examined macrophages investigated NF-kB signaling pathway specimens obtained from heads animals humans. We found that number GA-ONFH patients grew significantly, mice remarkably increase, maintaining high intramedullary. vitro, macrophage-conditioned elicited apoptosis BMSCs MLO-Y4 cells, shedding light intricate interplay between these cell types. The presence TNF-α within activated NF-κB pathway, providing mechanistic insight into apoptotic induction. employing robust rat macrophage clearance model model, demonstrated remarkable attenuation expression subsequent clearance. This pronounced reduction engenders diminished cellular decelerated trajectory progression. conclusion, our study reveals crucial involvement GA-ONFH, highlighting their indispensable disease Furthermore, early emerges promising strategy for impeding development GA-ONFH.

Language: Английский

Citations

11
Novel Clinical Insights into the Pathogenesis of Posttraumatic Elbow Stiffness: An Expression Profile Analysis of Contracted Joint Capsule in Human DOI Creative Commons
Nan Liu, Jinlei Dong, Lianxin Li

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 167 - 182

Published: Jan. 1, 2025

Posttraumatic elbow stiffness is a complex complication with two characteristics of capsular contracture and heterotopic ossification. Currently, genomic mechanisms pathogenesis posttraumatic remain inadequately understood. This study aims to identify differentially expressed genes (DEGs) elucidate molecular networks stiffness, providing novel insights into disease at transcriptome level. Global sequencing was conducted on six samples from individuals three control fractures. Differentially (DEGs), microRNAs, long non-coding RNAs (LncRNAs) were identified analyzed. Functional enrichment analysis performed, the associated protein-protein interaction (PPI) network constructed. MicroRNAs targeting these DEGs identified, transcription factors (TFs) predicted using ENCODE database. Finally, key validated by quantitative real-time polymerase chain reaction (qRT-PCR). A total 4909 protein-coding, LncRNA microRNA detected, including 2124 upregulated 2785 downregulated. Kyoto Encyclopedia Genes Genomes (KEGG) pathway revealed that significantly enriched in 36 signaling pathways, notably involving inflammatory responses extracellular matrix (ECM) receptor interactions. The highlighted such as SPP1, IBSP, MMP13 MYO1A having higher degrees connectivity. Key microRNAs (hsa-miR-186-5p, hsa-miR-515-5p, hsa-miR-590-3p) (TFDP1 STAT3) be implicated through microRNA-transcription factor regulatory analysis. provided underlying changes contracted capsules stiffness. Hub MMP13, MYO1A, (has-miR-186-5p, has-miR-515-5p, TFs may serve prognostic therapeutic targets provide new idea for future research direction clinical treatment.

Language: Английский

Citations

0
Astaxanthin Prevents Glucocorticoid-Induced Femoral Head Osteonecrosis by Targeting Ferroptosis through the JAK2/STAT3 Signaling Pathway DOI

Yuzhe Lin,

Zi-hao Chen,

Jianfeng Yang

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Glucocorticoid (GC) is extensively used in clinical practice, and the osteonecrosis of femoral head caused by them a common issue orthopedic surgery, yet underlying mechanisms remain unclear. Astaxanthin (AST), potent natural antioxidant, has an unexplored impact on GC-induced (GIONFH). This study explores effects AST counteracting dexamethasone (Dex)-induced ferroptosis GIONFH. We developed rat model GIONFH using intraperitoneal Dex injections conducted vitro analysis culturing osteoblasts (OBs) with treatment. assessed Dex-treated OBs C11-BODIPY FerroOrange staining, mitochondrial functionality tests, protein expression analyses through Western blot immunofluorescence. The influence bone microarchitecture was micro-CT, hematoxylin eosin immunofluorescence, immunohistochemistry at imaging histological levels. Our findings suggest that exerts inhibitory effect Dex-induced In vitro, treatment increased glutathione decreased malondialdehyde, lipid peroxidation, mitochondrial-reactive oxygen species. Additionally, also enhances phosphorylation STAT3, upregulates peroxidase 4 osteogenic-related proteins, stimulates formation. To delve deeper into mechanism, revealed triggered activation JAK2/STAT3 signaling. Moreover, use siRNA-STAT3 blocked beneficial cultivated Dex. brief, combats activating pathway to inhibit ferroptosis.

Language: Английский

Citations

0
Crosstalk Between H-Type Vascular Endothelial Cells and Macrophages: A Potential Regulator of Bone Homeostasis DOI Creative Commons

Jiaxuan Fan,

Yaohui Xie,

Dayin Liu

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 2743 - 2765

Published: Feb. 1, 2025

The crosstalk between H-type endothelial cells (ECs) and macrophages is critical for maintaining angiogenesis osteogenesis in bone homeostasis. As core components of type H vessels, ECs respond to various pro-angiogenic signals, forming specialized vascular structures characterized by high expression platelet-endothelial cell adhesion molecule-1 (CD31) mucin (EMCN), thereby facilitating angiogenesis-osteogenesis coupling during formation. Macrophages, as key immune the perivascular region, are primarily classified into classically activated pro-inflammatory M1 phenotype selectively anti-inflammatory M2 phenotype, performing dual functions regulating local tissue homeostasis innate immunity. In recent years, complex vessel has garnered significant interest context bone-related diseases. Orderly regulation immunity provides a new direction preventing metabolic disorders such osteoporosis osteoarthritis. However, their interactions remain insufficiently understood, with limited clinical data available. This review comprehensively examines intricate diverse phenotypes, Insights signaling pathways that regulate crosstalk, focusing on roles osteogenesis. Furthermore, discusses interventions targeting this challenges remain. These insights may offer perspectives provide theoretical foundation developing novel therapeutic strategies.

Language: Английский

Citations

0
Mechanistic Insights into Salvigenin for Glucocorticoid-Induced Femoral Head Osteonecrosis: A Network Pharmacology and Experimental Study DOI Creative Commons

Zhengjie Zhu,

Yujian Zhong, Ruyuan He

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 614 - 614

Published: March 3, 2025

Background/Objectives: Glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) is a debilitating condition resulting from impaired bone metabolism and vascular disruption due to prolonged glucocorticoid use. This study aimed explore therapeutic potential salvigenin, flavonoid with antioxidative estrogen-like properties, in alleviating GIOFH by modulating estrogen receptor alpha (ESR1) pathways. Methods: A network pharmacology approach was utilized identify salvigenin’s targets their association GIOFH. Protein–protein interaction networks, along Gene Ontology KEGG pathway analyses, were conducted clarify multi-target mechanisms. Molecular docking dynamics simulations assessed between salvigenin ESR1. Experimental validation included vitro assays on MG63 cells treated dexamethasone (Dex) mimic GIOFH, evaluating oxidative stress, apoptosis, osteogenic differentiation, ESR1 expression. Results: Network analysis identified ESR1, NOS3, MMP9 as key hub salvigenin. confirmed stable binding Salvigenin significantly reduced Dex-induced stress apoptosis osteoblasts while restoring differentiation Functional showed improved mineralized nodule formation, ALP activity, mitochondrial integrity salvigenin-treated cells. Conclusions: exhibits significant addressing through ESR1-mediated These results offer strong foundation for future translational studies development salvigenin-based therapies glucocorticoid-induced disorders.

Language: Английский

Citations

0