IL-18-Mediated SLC7A5 Overexpression Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells via the c-MYC Pathway

Ni, Feifei; Zhang, Tao; Xiao, Wan'an; Dong, Hong; Gao, Jian; Liu, YaFeng; Li, Jianjun

doi:10.3389/fcell.2021.748831

Cited by 5 publications

(5 citation statements)

References 48 publications

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“…We further observed downregulation of many other amino acid transporters such as Slc1a5 and Slc7a5 by long-term hyperglycemia. The lack of these two glutamine transporters has been associated with impaired differentiation of osteoblasts ( Ni et al, 2021 ; Sharma et al, 2021 ; Shen et al, 2021 ) indicating that the glutamine/glutamate to proline ratio may be important for osteoblast differentiation and proliferation.…”

Section: Discussionmentioning

confidence: 99%

Short- and long-term exposure to high glucose induces unique transcriptional changes in osteoblasts in vitro

Jalava,

Arponen,

Widjaja

et al. 2024

Biology Open

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Bone is increasingly recognized as a target for diabetic complications. In order to evaluate the direct effects of high glucose on bone, we investigated the global transcriptional changes induced by hyperglycemia in osteoblasts in vitro. Rat bone marrow-derived mesenchymal stromal cells were differentiated into osteoblasts for 10 days, and prior to analysis, they were exposed to hyperglycemia (25 mM) for the short-term (1 or 3 days) or long-term (10 days). Genes and pathways regulated by hyperglycemia were identified using mRNA sequencing and verified with qPCR. Genes upregulated by 1-day hyperglycemia were, for example, related to extracellular matrix organization, collagen synthesis and bone formation. This stimulatory effect was attenuated by 3 days. Long-term exposure impaired osteoblast viability, and downregulated, for example, extracellular matrix organization and lysosomal pathways, and increased intracellular oxidative stress. Interestingly, transcriptional changes by different exposure times were mostly unique and only 89 common genes responding to glucose were identified. In conclusion, short-term hyperglycemia had a stimulatory effect on osteoblasts and bone formation, whereas long-term hyperglycemia had a negative effect on intracellular redox balance, osteoblast viability and function.

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Section: Discussionmentioning

confidence: 99%

Short- and long-term exposure to high glucose induces unique transcriptional changes in osteoblasts in vitro

Jalava,

Arponen,

Widjaja

et al. 2024

Biology Open

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“…SLC7A5 and c-MYC play important roles in the IL-18-induced expression of osteogenic markers in hBMSCs. IL-18 upregulates the expression of SLC7A5 and c-MYC at the early stage of hBMSC osteogenic differentiation, and SLC7A5 and c-MYC inhibition blocks the osteogenic differentiation induced by IL-18 ( 34 ). The bone density of elderly patients with osteoporosis increases significantly after anti-osteoporosis treatment.…”

Section: Discussionmentioning

confidence: 99%

The causal role of circulating inflammatory markers in osteoporosis: a bidirectional Mendelian randomized study

Dong,

Wu,

Zhang

et al. 2024

Front. Immunol.

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BackgroundOsteoporosis (OP) associated with aging exerts substantial clinical and fiscal strains on societal structures. An increasing number of research studies have suggested a bidirectional relationship between circulating inflammatory markers (CIMs) and OP. However, observational studies are susceptible to perturbations in confounding variables. In contrast, Mendelian randomization (MR) offers a robust methodological framework to circumvent such confounders, facilitating a more accurate assessment of causality. Our study aimed to evaluate the causal relationships between CIMs and OP, identifying new approaches and strategies for the prevention, diagnosis and treatment of OP.MethodsWe analyzed publicly available GWAS summary statistics to investigate the causal relationships between CIMs and OP. Causal estimates were calculated via a systematic analytical framework, including bidirectional MR analysis and Bayesian colocalization analysis.ResultsGenetically determined levels of CXCL11 (OR = 0.91, 95% CI = 0.85–0.98, P = 0.008, PFDR = 0.119), IL-18 (OR = 0.88, 95% CI = 0.83–0.94, P = 8.66×10–5, PFDR = 0.008), and LIF (OR = 0.86, 95% CI = 0.76–0.96, P = 0.008, PFDR = 0.119) were linked to a reduced risk of OP. Conversely, higher levels of ARTN (OR = 1.11, 95% CI = 1.02–1.20, P = 0.012, PFDR = 0.119) and IFNG (OR = 1.16, 95% CI = 1.03–1.30, P = 0.013, PFDR = 0.119) were associated with an increased risk of OP. Bayesian colocalization analysis revealed no evidence of shared causal variants.ConclusionDespite finding no overall association between CIMs and OP, five CIMs demonstrated a potentially significant association with OP. These findings could pave the way for future mechanistic studies aimed at discovering new treatments for this disease. Additionally, we are the first to suggest a unidirectional causal relationship between ARTN and OP. This novel insight introduces new avenues for research into diagnostic and therapeutic strategies for OP.

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“…[ 59 ] Ni F. et al found that via the SLC7A5/c-MYC pathway IL-18 promoted the osteogenic differentiation of hBMSCs, which showed that MYC was also an important factor in osteogenic differentiation. [ 60 ] TNF-α can regulate the early development of ONFH by mediating osteoblast autophagy and apoptosis [ 61 ] and the onset of steroid-induced osteonecrosis of femoral head is influenced by TNF-α and hypoxia history, [ 62 ] so TNF is an important target of ONFH. IL6 is an important cytokine and ONFH is accompanied by significant inflammatory response, so IL6 is an important target in the process of ONFH.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology-based and molecular docking-based analysis of You-Gui-Yin for the treatment of osteonecrosis of the femoral head

Yao,

Fan,

Song

et al. 2023

Medicine

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You-Gui-Yin (YGY) is a classic prescription for warming up kidney-Yang and filling in kidney essence in traditional Chinese medicine, and has been used to treat osteonecrosis of the femoral head (ONFH) effectively. However, the underlying mechanisms are still unknown. This study is aimed at exploring the possible mechanisms of action of the YGY in the treatment of ONFH based on network pharmacology and molecular docking. TCMSP was used to screen the active components and targets of YGY. The disease targets of ONFH were collected in several public databases. The protein-protein interaction (PPI) Network was constructed using the STRING platform. The Metascape database platform was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The key active components and core target proteins of YGY in the treatment of ONFH were verified by the molecular docking. 120 active components were obtained from YGY, among which 73 components were hit by the 117 drug-disease intersection targets. Key effective components included quercetin, kaempferol, beta-sitosterol, glycitein, beta-carotene, and so on. Core target proteins included ALB, AKT1, TNF, IL6, TP53, and so on. According to GO and KEGG analyses, there were 1762 biological processes, 94 cellular component, 138 molecular function and 187 signaling pathways involved. we selected the top 20 biological processes (BP), cellular components (CC), molecular functions (MF) and signaling pathways to draw the heat maps, showing that Lipid and atherosclerosis signaling pathway, IL-17 signaling pathway, HIF-1 signaling pathway, relaxin signaling pathway and MAPK signaling pathway and other pathways may play a key role in the treatment of ONFH by YGY. The results of molecular docking showed that key effective components and corresponding core target proteins exhibited the good binding activity. YGY can treat ONFH through multicomponents, multitargets, and multipathways, which provides a reference for the subsequent research, development of targeted drugs and clinical application.

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IL-18-Mediated SLC7A5 Overexpression Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells via the c-MYC Pathway

Cited by 5 publications

References 48 publications

Short- and long-term exposure to high glucose induces unique transcriptional changes in osteoblasts in vitro

Short- and long-term exposure to high glucose induces unique transcriptional changes in osteoblasts in vitro

The causal role of circulating inflammatory markers in osteoporosis: a bidirectional Mendelian randomized study

Network pharmacology-based and molecular docking-based analysis of You-Gui-Yin for the treatment of osteonecrosis of the femoral head

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