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Occurrence and role of Tph cells in various renal diseases. Tph 细胞在各种肾病中的出现和作用。
IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-11 DOI: 10.1186/s10020-024-00919-3
Junyi Ren, Kuai Ma, Xiangheng Lu, Haoyu Peng, Jia Wang, Moussa Ide Nasser, Chi Liu

A new population of peripheral helper T (Tph) cells has been identified and contributed to various autoimmune diseases. Tph cells can secrete interleukin-21 (IL-21), interferon (IFN) and C-X-C motif chemokine ligand 13 (CXCL13) to moderate renal disease. Moreover, Tph cells can congregate in huge numbers and immerse within inflamed tissue. Compared to Tfh cells, Tph cells express high programmed cell death protein 1 (PD-1), major histocompatibility complex II (MHC-II), C-C chemokine receptor 2 (CCR2) and C-C chemokine receptor 5 (CCR5) but often lack expression of the chemokine receptor C-X-C chemokine receptor 5 (CXCR5). They display features distinct from other T cells, which are uniquely poised to promote responses and antibody production of B cells within pathologically inflamed non-lymphoid tissues and a key feature of Tph cells. In this review, we summarize recent findings on the role of Tph cells in chronic kidney disease, acute kidney injury, kidney transplantation and various renal diseases.

人们发现了一种新的外周辅助性 T 细胞(Tph)群体,它们是各种自身免疫性疾病的诱因。Tph 细胞能分泌白细胞介素-21(IL-21)、干扰素(IFN)和 C-X-C motif 趋化因子配体 13(CXCL13),从而缓解肾脏疾病。此外,Tph 细胞能大量聚集并浸入发炎组织。与Tfh细胞相比,Tph细胞高表达程序性细胞死亡蛋白1(PD-1)、主要组织相容性复合体II(MHC-II)、C-C趋化因子受体2(CCR2)和C-C趋化因子受体5(CCR5),但往往缺乏趋化因子受体C-X-C趋化因子受体5(CXCR5)的表达。它们显示出与其他 T 细胞不同的特征,在病理发炎的非淋巴组织中促进 B 细胞的反应和抗体生成,是 Tph 细胞的一个独特特征。在这篇综述中,我们总结了 Tph 细胞在慢性肾病、急性肾损伤、肾移植和各种肾病中的作用的最新发现。
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引用次数: 0
Drp1 acetylation mediated by CDK5-AMPK-GCN5L1 axis promotes cerebral ischemic injury via facilitating mitochondrial fission. CDK5-AMPK-GCN5L1轴介导的Drp1乙酰化通过促进线粒体裂变促进脑缺血损伤。
IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-10 DOI: 10.1186/s10020-024-00948-y
Jiejie Zhang, Shan Wang, Haitao Zhang, Xiaotong Yang, Xin Ren, Lei Wang, Yihan Yang, Yi Yang, Ya Wen

The aberrant acetylation of mitochondrial proteins is involved in the pathogenesis of multiple diseases including neurodegenerative diseases and cerebral ischemic injury. Previous studies have shown that depletion of mitochondrial NAD+, which is necessary for mitochondrial deacetylase activity, leads to decreased activity of mitochondrial deacetylase and thus causes hyperacetylation of mitochondrial proteins in ischemic brain tissues, which results in altered mitochondrial dynamics. However, it remains largely unknown about how mitochondrial dynamics-related protein Drp1 is acetylated in ischemic neuronal cells and brain tissues. Here, we showed that Drp1 and GCN5L1 expression was up-regulated in OGD-treated neuronal cells and ischemic brain tissues induced by dMCAO, accompanied by the increased mitochondrial fission, mtROS accumulation, and cell apoptosis. Further, we confirmed that ischemia/hypoxia promoted Drp1 interaction with GCN5L1 in neuronal cells and brain tissues. GCN5L1 knockdown attenuated, while its overexpression enhanced Drp1 acetylation and mitochondrial fission, indicating that GCN5L1 plays a crucial role in ischemia/hypoxia-induced mitochondrial fission by acetylating Drp1. Mechanistically, ischemia/hypoxia induced Drp1 phosphorylation by CDK5 upregulation-mediated activation of AMPK in neuronal cells, which in turn facilitated the interaction of GCN5L1 with Drp1, thus enhancing Drp1 acetylation and mitochondrial fission. Accordingly, inhibition of AMPK alleviated ischemia/hypoxia- induced Drp1 acetylation and mitochondrial fission and protected brain tissues from ischemic damage. These findings provide a novel insight into the functional roles of GCN5L1 in regulating Drp1 acetylation and identify a previously unrecognized CDK5-AMPK-GCN5L1 pathway that mediates the acetylation of Drp1 in ischemic brain tissues.

线粒体蛋白的乙酰化异常与神经退行性疾病和脑缺血损伤等多种疾病的发病机制有关。先前的研究表明,线粒体脱乙酰化酶活性所必需的线粒体 NAD+ 的耗竭会导致线粒体脱乙酰化酶活性降低,从而引起缺血性脑组织中线粒体蛋白的高乙酰化,导致线粒体动力学改变。然而,线粒体动力学相关蛋白Drp1在缺血性神经元细胞和脑组织中如何发生乙酰化,目前仍是一个未知数。在这里,我们发现,Drp1和GCN5L1在OGD处理的神经元细胞和dMCAO诱导的缺血脑组织中表达上调,并伴随线粒体裂变、mtROS积累和细胞凋亡的增加。此外,我们还证实缺血/缺氧促进了神经元细胞和脑组织中 Drp1 与 GCN5L1 的相互作用。GCN5L1敲除可减轻Drp1的乙酰化,而过表达则可增强Drp1的乙酰化和线粒体裂解,这表明GCN5L1通过乙酰化Drp1在缺血缺氧诱导的线粒体裂解中起着关键作用。从机理上讲,缺血/缺氧通过CDK5上调激活AMPK诱导神经细胞中的Drp1磷酸化,进而促进GCN5L1与Drp1的相互作用,从而增强Drp1乙酰化和线粒体裂解。因此,抑制 AMPK 可缓解缺血/缺氧诱导的 Drp1 乙酰化和线粒体分裂,保护脑组织免受缺血损伤。这些发现为了解 GCN5L1 在调控 Drp1 乙酰化中的功能作用提供了新的视角,并确定了一种之前未被认识的 CDK5-AMPK-GCN5L1 通路,该通路介导缺血脑组织中 Drp1 的乙酰化。
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引用次数: 0
Acetylcholine receptor-β inhibition by interleukin-6 in skeletal muscles contributes to modulating neuromuscular junction during aging. 白细胞介素-6对骨骼肌乙酰胆碱受体-β的抑制有助于调节衰老过程中的神经肌肉接头。
IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-10 DOI: 10.1186/s10020-024-00943-3
Yanling Zhao, Han Yan, Ke Liu, Jiangping Ma, Wenlan Sun, Hejin Lai, Hongli Li, Jianbang Gu, He Huang

Background: Aging-related strength decline contributes to physiological deterioration and is a good predictor of poor prognosis. However, the mechanisms underlying neuromuscular junction disorders affecting contraction in aging are not well described. We hypothesized that the autocrine effect of interleukin (IL)-6 secreted by skeletal muscle inhibits acetylcholine receptor (AChR) expression, potentially causing aging-related strength decline. Therefore, we investigated IL-6 and AChR β-subunit (AChR-β) expression in the muscles and sera of aging C57BL/6J mice and verified the effect of IL-6 on AChR-β expression.

Methods: Animal experiments, in vitro studies, bioinformatics, gene manipulation, dual luciferase reporter gene assays, and chromatin immunoprecipitation experiments were used to explore the role of the transcription cofactor peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) and its interacting transcription factors in the IL-6-mediated regulation of AChR-β expression.

Results: IL-6 expression gradually increased during aging, inhibiting AChR-β expression, which was reversed by tocilizumab. Both tocilizumab and the PGC1α agonist reversed the inhibiting effect of IL-6 expression on AChR-β. Compared to inhibition of signal transducer and activator of transcription 3, extracellular signal-regulated kinases 1/2 (ERK1/2) inhibition suppressed the effects of IL-6 on AChR-β and PGC1α. In aging mouse muscles and myotubes, myocyte enhancer factor 2 C (MEF2C) was recruited by PGC1α, which directly binds to the AChR-β promoter to regulate its expression.

Conclusions: This study verifies AChR-β regulation by the IL-6/IL-6R-ERK1/2-PGC1α/MEF2C pathway. Hence, evaluating muscle secretion, myokines, and AChRs at an earlier stage to determine pathological progression is important. Moreover, developing intervention strategies for monitoring, maintaining, and improving muscle structure and function is necessary.

背景:与衰老相关的力量衰退会导致生理机能退化,是预后不良的良好预兆。然而,影响衰老收缩的神经肌肉接头紊乱的机制尚未得到很好的描述。我们假设,骨骼肌分泌的白细胞介素(IL)-6 的自分泌效应会抑制乙酰胆碱受体(AChR)的表达,从而可能导致与衰老相关的力量下降。因此,我们研究了 IL-6 和 AChR β-亚基(AChR-β)在衰老的 C57BL/6J 小鼠肌肉和血清中的表达,并验证了 IL-6 对 AChR-β 表达的影响:方法:采用动物实验、体外研究、生物信息学、基因操作、双荧光素酶报告基因检测和染色质免疫沉淀实验等方法,探讨转录辅助因子过氧化物酶体增殖激活受体γ辅助激活因子1-α(PGC1α)及其相互作用的转录因子在IL-6介导的AChR-β表达调控中的作用:结果:IL-6的表达在衰老过程中逐渐增加,抑制了AChR-β的表达,而托珠单抗可逆转这种抑制。托西珠单抗和 PGC1α 激动剂都能逆转 IL-6 表达对 AChR-β 的抑制作用。与抑制信号转导和转录激活因子3相比,抑制细胞外信号调节激酶1/2(ERK1/2)可抑制IL-6对AChR-β和PGC1α的影响。在衰老的小鼠肌肉和肌管中,肌细胞增强因子2 C(MEF2C)被PGC1α招募,后者直接与AChR-β启动子结合,调控其表达:本研究验证了 AChR-β 受 IL-6/IL-6R-ERK1/2-PGC1α/MEF2C 通路的调控。因此,在早期阶段评估肌肉分泌、肌动素和 AChRs 以确定病理进展非常重要。此外,制定监测、维持和改善肌肉结构与功能的干预策略也很有必要。
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引用次数: 0
ELAVL1 regulates glycolysis in nasopharyngeal carcinoma cells through the HMGB3/β-catenin axis. ELAVL1通过HMGB3/β-catenin轴调节鼻咽癌细胞的糖酵解。
IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-10 DOI: 10.1186/s10020-024-00941-5
Yi Cui, Haojie Wen, Jinyong Tang, Jiawen Chen, Juan Zhou, Minghua Hou, Xiaohan Rong, Yuanzhao Lan, Qiong Wu

Background: The role of ELAVL1 in the progression of various tumors has been demonstrated. Our research aims to investigate how ELAVL1 controls the glycolytic process in nasopharyngeal carcinoma cells through the HMGB3/β-catenin pathway.

Methods: The expression of ELAVL1 was detected in clinical tumor samples and nasopharyngeal carcinoma cell lines. A subcutaneous tumor model was established in nude mice to investigate the role of ELAVL1 in tumor progression. The relationship between HMGB3 and ELAVL1 was validated by RNA pull down and RIP assays. TOPFlash/FOPFlash reporter assay was used to detect β-catenin activity. Assay kits were utilized to measure glucose consumption, lactate production, and G6PD activity in nasopharyngeal carcinoma cells. Western blot was conducted to detect the expression of glycolysis-related proteins. The glycolytic capacity was analyzed through extracellular acidification rate (ECAR).

Results: In both clinical samples and nasopharyngeal carcinoma cell lines, the expression levels of ELAVL1 mRNA and protein were found to be upregulated. Knockdown of ELAVL1 significantly inhibited the in vivo proliferation of nasopharyngeal carcinoma and suppressed the glycolytic capacity of nasopharyngeal carcinoma cells. ELAVL1 interacts with HMGB3, leading to an increase in the stability of HMGB3 mRNA. Overexpression of HMGB3 elevated the reduced β-catenin activity caused by sh-ELAVL1 and reversed the inhibitory effect of sh-ELAVL1 on cellular glycolytic capacity. Treatment with β-catenin inhibitor (FH535) effectively suppressed the promotion of glycolytic capacity induced by HMGB3 overexpression.

Conclusions: ELAVL1 promotes glycolysis in nasopharyngeal carcinoma cells by interacting with HMGB3 to stabilize HMGB3 mRNA, thereby activating β-catenin pathway. Therefore, targeting the ELAVL1-HMGB3-β-catenin axis has the potential to be a novel approach for treating nasopharyngeal carcinoma.

背景:ELAVL1在多种肿瘤进展中的作用已被证实。我们的研究旨在探讨 ELAVL1 如何通过 HMGB3/β-catenin 通路控制鼻咽癌细胞的糖酵解过程:方法:在临床肿瘤样本和鼻咽癌细胞系中检测ELAVL1的表达。建立裸鼠皮下肿瘤模型,研究 ELAVL1 在肿瘤进展中的作用。通过 RNA pull down 和 RIP 试验验证了 HMGB3 和 ELAVL1 之间的关系。TOPFlash/FOPFlash报告实验用于检测β-catenin的活性。检测试剂盒用于测量鼻咽癌细胞的葡萄糖消耗、乳酸生成和 G6PD 活性。通过 Western 印迹检测糖酵解相关蛋白的表达。通过细胞外酸化率(ECAR)分析糖酵解能力:结果:在临床样本和鼻咽癌细胞系中,ELAVL1 mRNA和蛋白质的表达水平均上调。敲除 ELAVL1 能显著抑制鼻咽癌的体内增殖,并抑制鼻咽癌细胞的糖酵解能力。ELAVL1 与 HMGB3 相互作用,导致 HMGB3 mRNA 的稳定性增加。过量表达HMGB3可提高sh-ELAVL1导致的β-catenin活性降低,并逆转sh-ELAVL1对细胞糖酵解能力的抑制作用。β-catenin抑制剂(FH535)能有效抑制HMGB3过表达对糖酵解能力的促进作用:结论:ELAVL1通过与HMGB3相互作用稳定HMGB3 mRNA,从而激活β-catenin通路,促进鼻咽癌细胞的糖酵解。因此,靶向 ELAVL1-HMGB3-β-catenin 轴有可能成为治疗鼻咽癌的一种新方法。
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引用次数: 0
Metabolic effects of quercetin on inflammatory and autoimmune responses in rheumatoid arthritis are mediated through the inhibition of JAK1/STAT3/HIF-1α signaling. 槲皮素通过抑制 JAK1/STAT3/HIF-1α 信号传导,对类风湿性关节炎的炎症和自身免疫反应产生代谢影响。
IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-10 DOI: 10.1186/s10020-024-00929-1
FengQi Zhang, YiYang Zhang, JiaWang Zhou, Ying Cai, ZhiYu Li, Jing Sun, ZhiJun Xie, GuiFeng Hao
<p><strong>Background: </strong>Rheumatoid arthritis, a chronic autoimmune disease, is characterized by synovial hyperplasia and cartilage erosion. Here, we investigated the potential mechanism of action of quercetin, the main component of flavonoids, in treating rheumatoid arthritis.</p><p><strong>Object: </strong>To examine the anti-arthritic effects of quercetin and elucidate the specific mechanisms that differentiate its metabolic effects on autoimmune and inflammatory responses at the synovial cell level.</p><p><strong>Methods: </strong>We created a collagen-induced arthritis (CIA) model in Wistar rats, which were administered quercetin (50 or 100 mg/kg) continuously for four weeks via stomach perfusion. The arthritis score, histopathological staining, radiological assessment, and serum biochemical parameters were used to study the impact of quercetin on disease improvement. Additionally, immunofluorescence was employed to detect JAK1/STAT3/HIF-1α expression in rat joints. Moreover, the effects of quercetin (20, 40, and 80 µmol/L) on the properties and behavior of synovial fibroblasts were evaluated in an in vitro MH7A cell model using flow cytometry, CCK8, and transwell assays. Further, the mRNA expression levels of inflammatory cytokines IL1β, IL6, IL17, and TNFα were assessed by quantitative real-time PCR. Glucose, lactate, lactate dehydrogenase, pyruvate, pyruvate dehydrogenase, and adenosine triphosphate assay kits were employed to measure the metabolic effects of quercetin on synovial fibroblasts. Finally, immunoblotting was used to examine the impact of quercetin on the JAK1/STAT3/HIF-1α signaling pathway in synovial fibroblasts.</p><p><strong>Results: </strong>In vivo experiments confirmed the favorable effects of quercetin in CIA rats, including an improved arthritis score and reduced ankle bone destruction, in addition to a decrease in the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in serum. Immunofluorescence verified that quercetin may ameliorate joint injury in rats with CIA by inhibiting JAK1/STAT3/HIF-1α signaling. Various in vitro experiments demonstrated that quercetin effectively inhibits IL-6-induced proliferation of MH7A cells and reduces their migratory and invasive behavior, while inducing apoptosis and reducing the expression of the pro-inflammatory cytokines IL1β, IL6, IL17, and TNFα at the mRNA level. Quercetin caused inhibition of glucose, lactate, lactate dehydrogenase, pyruvate, and adenosine triphosphate and increased pyruvate dehydrogenase expression in MH7A cells. It was further confirmed that quercetin may inhibit energy metabolism and inflammatory factor secretion in MH7A cells through JAK1/STAT3/HIF-1α signaling.</p><p><strong>Conclusions: </strong>Quercetin's action on multiple target molecules and pathways makes it a promising treatment for cartilage injury in rheumatoid arthritis. By reducing joint inflammation, improving joint metabolic homeostasis, and decreasing immune system activation e
背景:类风湿性关节炎是一种慢性自身免疫性疾病,以滑膜增生和软骨侵蚀为特征。在此,我们研究了类黄酮的主要成分槲皮素治疗类风湿性关节炎的潜在作用机制:目的:研究槲皮素的抗关节炎作用,并阐明其在滑膜细胞水平上对自身免疫和炎症反应的代谢作用的具体机制:方法:我们在Wistar大鼠体内建立了胶原蛋白诱导的关节炎(CIA)模型,通过胃灌注给大鼠连续服用槲皮素(50或100毫克/千克)四周。通过关节炎评分、组织病理学染色、放射学评估和血清生化指标来研究槲皮素对疾病改善的影响。此外,还采用免疫荧光法检测大鼠关节中 JAK1/STAT3/HIF-1α 的表达。此外,在体外 MH7A 细胞模型中,使用流式细胞术、CCK8 和透孔试验评估了槲皮素(20、40 和 80 µmol/L)对滑膜成纤维细胞特性和行为的影响。此外,还通过实时定量 PCR 评估了炎性细胞因子 IL1β、IL6、IL17 和 TNFα 的 mRNA 表达水平。葡萄糖、乳酸、乳酸脱氢酶、丙酮酸、丙酮酸脱氢酶和三磷酸腺苷检测试剂盒用于测量槲皮素对滑膜成纤维细胞代谢的影响。最后,免疫印迹法检测了槲皮素对滑膜成纤维细胞中 JAK1/STAT3/HIF-1α 信号通路的影响:体内实验证实了槲皮素对CIA大鼠的有利影响,包括改善关节炎评分和减少踝骨破坏,以及减少血清中的促炎细胞因子IL-1β、IL-6、IL-17和TNF-α。免疫荧光验证了槲皮素可通过抑制 JAK1/STAT3/HIF-1α 信号传导来改善 CIA 大鼠的关节损伤。各种体外实验表明,槲皮素能有效抑制 IL-6 诱导的 MH7A 细胞增殖,减少其迁移和侵袭行为,同时诱导细胞凋亡,并在 mRNA 水平上减少促炎细胞因子 IL1β、IL6、IL17 和 TNFα 的表达。槲皮素能抑制 MH7A 细胞中葡萄糖、乳酸、乳酸脱氢酶、丙酮酸和三磷酸腺苷的表达,并能增加丙酮酸脱氢酶的表达。研究进一步证实,槲皮素可通过JAK1/STAT3/HIF-1α信号传导抑制MH7A细胞的能量代谢和炎症因子分泌:结论:槲皮素对多种靶分子和途径的作用使其成为治疗类风湿性关节炎软骨损伤的一种有前途的疗法。通过减轻关节炎症、改善关节代谢平衡和降低免疫系统激活能量,槲皮素抑制了JAK1/STAT3/HIF-1α信号通路,从而改善了疾病状况。
{"title":"Metabolic effects of quercetin on inflammatory and autoimmune responses in rheumatoid arthritis are mediated through the inhibition of JAK1/STAT3/HIF-1α signaling.","authors":"FengQi Zhang, YiYang Zhang, JiaWang Zhou, Ying Cai, ZhiYu Li, Jing Sun, ZhiJun Xie, GuiFeng Hao","doi":"10.1186/s10020-024-00929-1","DOIUrl":"10.1186/s10020-024-00929-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Rheumatoid arthritis, a chronic autoimmune disease, is characterized by synovial hyperplasia and cartilage erosion. Here, we investigated the potential mechanism of action of quercetin, the main component of flavonoids, in treating rheumatoid arthritis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Object: &lt;/strong&gt;To examine the anti-arthritic effects of quercetin and elucidate the specific mechanisms that differentiate its metabolic effects on autoimmune and inflammatory responses at the synovial cell level.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We created a collagen-induced arthritis (CIA) model in Wistar rats, which were administered quercetin (50 or 100 mg/kg) continuously for four weeks via stomach perfusion. The arthritis score, histopathological staining, radiological assessment, and serum biochemical parameters were used to study the impact of quercetin on disease improvement. Additionally, immunofluorescence was employed to detect JAK1/STAT3/HIF-1α expression in rat joints. Moreover, the effects of quercetin (20, 40, and 80 µmol/L) on the properties and behavior of synovial fibroblasts were evaluated in an in vitro MH7A cell model using flow cytometry, CCK8, and transwell assays. Further, the mRNA expression levels of inflammatory cytokines IL1β, IL6, IL17, and TNFα were assessed by quantitative real-time PCR. Glucose, lactate, lactate dehydrogenase, pyruvate, pyruvate dehydrogenase, and adenosine triphosphate assay kits were employed to measure the metabolic effects of quercetin on synovial fibroblasts. Finally, immunoblotting was used to examine the impact of quercetin on the JAK1/STAT3/HIF-1α signaling pathway in synovial fibroblasts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In vivo experiments confirmed the favorable effects of quercetin in CIA rats, including an improved arthritis score and reduced ankle bone destruction, in addition to a decrease in the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in serum. Immunofluorescence verified that quercetin may ameliorate joint injury in rats with CIA by inhibiting JAK1/STAT3/HIF-1α signaling. Various in vitro experiments demonstrated that quercetin effectively inhibits IL-6-induced proliferation of MH7A cells and reduces their migratory and invasive behavior, while inducing apoptosis and reducing the expression of the pro-inflammatory cytokines IL1β, IL6, IL17, and TNFα at the mRNA level. Quercetin caused inhibition of glucose, lactate, lactate dehydrogenase, pyruvate, and adenosine triphosphate and increased pyruvate dehydrogenase expression in MH7A cells. It was further confirmed that quercetin may inhibit energy metabolism and inflammatory factor secretion in MH7A cells through JAK1/STAT3/HIF-1α signaling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Quercetin's action on multiple target molecules and pathways makes it a promising treatment for cartilage injury in rheumatoid arthritis. By reducing joint inflammation, improving joint metabolic homeostasis, and decreasing immune system activation e","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"170"},"PeriodicalIF":6.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rewriting cellular fate: epigenetic interventions in obesity and cellular programming. 改写细胞命运:肥胖和细胞编程中的表观遗传干预。
IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-10 DOI: 10.1186/s10020-024-00944-2
Rui-Lin Li, Sheng Kang

External constraints, such as development, disease, and environment, can induce changes in epigenomic patterns that may profoundly impact the health trajectory of fetuses and neonates into adulthood, influencing conditions like obesity. Epigenetic modifications encompass processes including DNA methylation, covalent histone modifications, and RNA-mediated regulation. Beyond forward cellular differentiation (cell programming), terminally differentiated cells are reverted to a pluripotent or even totipotent state, that is, cellular reprogramming. Epigenetic modulators facilitate or erase histone and DNA modifications both in vivo and in vitro during programming and reprogramming. Noticeably, obesity is a complex metabolic disorder driven by both genetic and environmental factors. Increasing evidence suggests that epigenetic modifications play a critical role in the regulation of gene expression involved in adipogenesis, energy homeostasis, and metabolic pathways. Hence, we discuss the mechanisms by which epigenetic interventions influence obesity, focusing on DNA methylation, histone modifications, and non-coding RNAs. We also analyze the methodologies that have been pivotal in uncovering these epigenetic regulations, i.e., Large-scale screening has been instrumental in identifying genes and pathways susceptible to epigenetic control, particularly in the context of adipogenesis and metabolic homeostasis; Single-cell RNA sequencing (scRNA-seq) provides a high-resolution view of gene expression patterns at the individual cell level, revealing the heterogeneity and dynamics of epigenetic regulation during cellular differentiation and reprogramming; Chromatin immunoprecipitation (ChIP) assays, focused on candidate genes, have been crucial for characterizing histone modifications and transcription factor binding at specific genomic loci, thereby elucidating the epigenetic mechanisms that govern cellular programming; Somatic cell nuclear transfer (SCNT) and cell fusion techniques have been employed to study the epigenetic reprogramming accompanying cloning and the generation of hybrid cells with pluripotent characteristics, etc. These approaches have been instrumental in identifying specific epigenetic marks and pathways implicated in obesity, providing a foundation for developing targeted therapeutic interventions. Understanding the dynamic interplay between epigenetic regulation and cellular programming is crucial for advancing mechanism and clinical management of obesity.

发育、疾病和环境等外部制约因素会诱发表观基因组模式的变化,这些变化可能会对胎儿和新生儿成年后的健康轨迹产生深远影响,进而影响肥胖等疾病。表观遗传修饰包括 DNA 甲基化、共价组蛋白修饰和 RNA 介导的调控等过程。除了前向细胞分化(细胞编程)外,终末分化的细胞还能恢复到多能甚至全能状态,即细胞重编程。在体内和体外编程和重编程过程中,表观遗传调节剂可促进或消除组蛋白和 DNA 的修饰。值得注意的是,肥胖症是一种复杂的代谢性疾病,由遗传和环境因素共同驱动。越来越多的证据表明,表观遗传修饰在调控涉及脂肪生成、能量平衡和代谢途径的基因表达方面发挥着关键作用。因此,我们讨论了表观遗传干预影响肥胖的机制,重点是 DNA 甲基化、组蛋白修饰和非编码 RNA。我们还分析了揭示这些表观遗传调控的关键方法,即.....、大规模筛选有助于确定易受表观遗传调控的基因和通路,尤其是在脂肪生成和代谢平衡的背景下;单细胞 RNA 测序(scRNA-seq)提供了单个细胞水平基因表达模式的高分辨率视图,揭示了细胞分化和重编程过程中表观遗传调控的异质性和动态性;以候选基因为重点的染色质免疫共沉淀(ChIP)测定对于描述特定基因组位点的组蛋白修饰和转录因子结合至关重要,从而阐明了细胞编程的表观遗传学机制;体细胞核移植(SCNT)和细胞融合技术已被用于研究伴随克隆产生的表观遗传学重编程以及具有多能特性的杂交细胞的产生等。这些方法有助于确定与肥胖有关的特定表观遗传标记和通路,为开发有针对性的治疗干预措施奠定了基础。了解表观遗传调控和细胞编程之间的动态相互作用,对于推进肥胖症的机制和临床治疗至关重要。
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引用次数: 0
Enhanced spinal cord repair using bioengineered induced pluripotent stem cell-derived exosomes loaded with miRNA. 利用负载 miRNA 的生物工程诱导多能干细胞衍生外泌体增强脊髓修复。
IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 10.1186/s10020-024-00940-6
Azar Abbas, Xiaosheng Huang, Aftab Ullah, Lishi Luo, Wenqun Xi, Yuanjiao Qiao, Kun Zeng

Background: A spinal cord injury (SCI) can result in severe impairment and fatality as well as significant motor and sensory abnormalities. Exosomes produced from IPSCs have demonstrated therapeutic promise for accelerating spinal cord injury recovery, according to a recent study.

Objective: This study aims to develop engineered IPSCs-derived exosomes (iPSCs-Exo) capable of targeting and supporting neurons, and to assess their therapeutic potential in accelerating recovery from spinal cord injury (SCI).

Methods: iPSCs-Exo were characterized using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. To enhance neuronal targeting, iPSCs-Exo were bioengineered, and their uptake by neurons was visualized using PKH26 labeling and fluorescence microscopy. In vitro, the anti-inflammatory effects of miRNA-loaded engineered iPSCs-Exo were evaluated by exposing neurons to LPS and IFN-γ. In vivo, biodistribution of engineered iPSC-Exo was monitored using a vivo imaging system. The therapeutic efficacy of miRNA-loaded engineered iPSC-Exo in a SCI mouse model was assessed by Basso Mouse Scale (BMS) scores, H&E, and Luxol Fast Blue (LFB) staining.

Results: The results showed that engineered iPSC-Exo loaded with miRNA promoted the spinal cord injure recovery. Thorough safety assessments using H&E staining on major organs revealed no evidence of systemic toxicity, with normal organ histology and biochemistry profiles following engineered iPSC-Exo administration.

Conclusion: These results suggest that modified iPSC-derived exosomes loaded with miRNA have great potential as a cutting-edge therapeutic approach to improve spinal cord injury recovery. The observed negligible systemic toxicity further underscores their potential safety and efficacy in clinical applications.

背景:脊髓损伤(SCI)可导致严重损伤和死亡,以及明显的运动和感觉异常。最近的一项研究表明,由 IPSCs 产生的外泌体有望加速脊髓损伤的恢复:本研究旨在开发能够靶向和支持神经元的工程化 IPSCs 衍生外泌体(iPSCs-Exo),并评估其在加速脊髓损伤(SCI)恢复方面的治疗潜力。方法:使用透射电子显微镜(TEM)、纳米粒子跟踪分析(NTA)和 Western 印迹对 iPSCs-Exo 进行表征。为增强神经元靶向性,对iPSCs-Exo进行了生物工程处理,并利用PKH26标记和荧光显微镜观察神经元对其的摄取。在体外,通过让神经元暴露于 LPS 和 IFN-γ,评估了加载 miRNA 的工程 iPSCs-Exo 的抗炎作用。在体内,利用体内成像系统监测了工程iPSC-Exo的生物分布。通过巴索小鼠量表(BMS)评分、H&E和卢克索快速蓝(LFB)染色评估了miRNA负载的工程iPSC-Exo在SCI小鼠模型中的疗效:结果表明,含有 miRNA 的工程 iPSC-Exo 促进了脊髓损伤的恢复。使用 H&E 染色法对主要器官进行彻底的安全性评估后,没有发现全身毒性的迹象,服用工程 iPSC-Exo 后器官组织学和生化指标正常:这些结果表明,作为一种改善脊髓损伤恢复的前沿治疗方法,含有 miRNA 的改良 iPSC 衍生外泌体具有巨大的潜力。观察到的可忽略不计的全身毒性进一步强调了其在临床应用中的潜在安全性和有效性。
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引用次数: 0
Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer. 整合网络药理学、分子对接和实验验证,探索诺米林对三阴性乳腺癌的治疗效果和潜在机制。
IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-28 DOI: 10.1186/s10020-024-00928-2
Zhixuan Wu, Haoyi Xiang, Xiaowu Wang, Rongrong Zhang, Yangyang Guo, Liangchen Qu, Jingyao Zhou, Yanyi Xiao

Background: Nomilin is a limonoid compound known for its multiple biological activities, but its role in triple negative breast cancer (TNBC) remains unclear. This study aims to uncover the potential therapeutic effect of nomilin on TNBC and elucidate the specific mechanism of its action.

Methods: We employed weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the GeneCards database to identify potential targets for TNBC. Simultaneously, we utilized the Swiss Target Prediction, ChEMBL, and STITCH databases to identify potential targets of nomilin. The core targets and mechanisms of nomilin against TNBC were predicted through protein-protein interaction (PPI) network analysis, molecular docking, and enrichment analysis. The results of the network pharmacology were corroborated by conducting experiments.

Results: A total of 17,204 TNBC targets were screened, and 301 potential targets of nomilin were identified. Through the PPI network, eight core targets of nomilin against TNBC were pinpointed, namely BCL2, Caspase3, CyclinD1, EGFR, HSP90AA1, KRAS, PARP1, and TNF. Molecular docking, molecular dynamics simulation and proteome microarray revealed that nomilin exhibits strong binding activity to these core proteins. Enrichment analysis results indicated that the anti-TNBC effect of nomilin is associated with PI3K/Akt pathway. In vitro and in vivo experiments have demonstrated that nomilin inhibits TNBC cell proliferation and migration while promoting cell apoptosis through the PI3K/Akt pathway.

Conclusion: For the first time, the research effectively discovered the objectives and mechanisms of nomilin in combating TNBC using network pharmacology, molecular docking, molecular dynamics simulation, proteome microarray and experimental confirmation, presenting a hopeful approach for treating TNBC.

背景:诺米林是一种具有多种生物活性的柠檬类化合物,但它在三阴性乳腺癌(TNBC)中的作用仍不清楚。本研究旨在揭示诺米林对 TNBC 的潜在治疗作用,并阐明其作用的具体机制:方法:我们采用加权基因共表达网络分析(WGCNA)、差异表达分析和GeneCards数据库来确定TNBC的潜在靶点。同时,我们还利用瑞士靶点预测、ChEMBL 和 STITCH 数据库来确定 nomilin 的潜在靶点。通过蛋白-蛋白相互作用(PPI)网络分析、分子对接和富集分析,我们预测了诺米林对TNBC的核心靶点和作用机制。实验证实了网络药理学的结果:结果:共筛选出17204个TNBC靶点,发现了301个Nomilin的潜在靶点。结果:共筛选出17204个TNBC靶点,并确定了301个nomilin的潜在靶点。通过PPI网络,确定了nomilin抗TNBC的8个核心靶点,即BCL2、Caspase3、CyclinD1、EGFR、HSP90AA1、KRAS、PARP1和TNF。分子对接、分子动力学模拟和蛋白质组芯片显示,Nomilin 与这些核心蛋白具有很强的结合活性。富集分析结果表明,nomilin 的抗肿瘤作用与 PI3K/Akt 通路有关。体外和体内实验证明,nomilin能抑制TNBC细胞的增殖和迁移,同时通过PI3K/Akt通路促进细胞凋亡:该研究首次利用网络药理学、分子对接、分子动力学模拟、蛋白质组芯片和实验证实等方法,有效地发现了nomilin对抗TNBC的目的和机制,为治疗TNBC提供了一种有希望的方法。
{"title":"Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer.","authors":"Zhixuan Wu, Haoyi Xiang, Xiaowu Wang, Rongrong Zhang, Yangyang Guo, Liangchen Qu, Jingyao Zhou, Yanyi Xiao","doi":"10.1186/s10020-024-00928-2","DOIUrl":"https://doi.org/10.1186/s10020-024-00928-2","url":null,"abstract":"<p><strong>Background: </strong>Nomilin is a limonoid compound known for its multiple biological activities, but its role in triple negative breast cancer (TNBC) remains unclear. This study aims to uncover the potential therapeutic effect of nomilin on TNBC and elucidate the specific mechanism of its action.</p><p><strong>Methods: </strong>We employed weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the GeneCards database to identify potential targets for TNBC. Simultaneously, we utilized the Swiss Target Prediction, ChEMBL, and STITCH databases to identify potential targets of nomilin. The core targets and mechanisms of nomilin against TNBC were predicted through protein-protein interaction (PPI) network analysis, molecular docking, and enrichment analysis. The results of the network pharmacology were corroborated by conducting experiments.</p><p><strong>Results: </strong>A total of 17,204 TNBC targets were screened, and 301 potential targets of nomilin were identified. Through the PPI network, eight core targets of nomilin against TNBC were pinpointed, namely BCL2, Caspase3, CyclinD1, EGFR, HSP90AA1, KRAS, PARP1, and TNF. Molecular docking, molecular dynamics simulation and proteome microarray revealed that nomilin exhibits strong binding activity to these core proteins. Enrichment analysis results indicated that the anti-TNBC effect of nomilin is associated with PI3K/Akt pathway. In vitro and in vivo experiments have demonstrated that nomilin inhibits TNBC cell proliferation and migration while promoting cell apoptosis through the PI3K/Akt pathway.</p><p><strong>Conclusion: </strong>For the first time, the research effectively discovered the objectives and mechanisms of nomilin in combating TNBC using network pharmacology, molecular docking, molecular dynamics simulation, proteome microarray and experimental confirmation, presenting a hopeful approach for treating TNBC.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"166"},"PeriodicalIF":6.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in hematological diseases. 血液病中的胰岛素样生长因子 2 mRNA 结合蛋白 1 (IGF2BP1)。
IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-28 DOI: 10.1186/s10020-024-00936-2
Shuangping Ma, Yiran Qin, Wenjie Ren

The oncofetal mRNA-binding protein IGF2BP1 belongs to a conserved family of RNA-binding proteins. It primarily promotes RNA stability, regulates translation and RNA localization, and mediates gene expression through its downstream effectors. Numerous studies have demonstrated that IGF2BP1 plays crucial roles in embryogenesis and carcinogenesis. IGF2BP1-modulated cell proliferation, invasion, and chemo-resistance in solid tumors have attracted researchers' attention. Additionally, several studies have highlighted the importance of IGF2BP1 in hematologic malignancies and hematological genetic diseases, positioning it as a promising therapeutic target for hematological disorders. However, there is a lack of systematic summaries regarding the IGF2BP1 gene within the hematological field. In this review, we provide a comprehensive overview of the discovery and molecular structure of IGF2BP1, along with recent studies on its role in regulating embryogenesis. We also focus on the mechanisms by which IGF2BP1 regulates hematological malignancies through its interactions with its targeted mRNAs. Furthermore, we systematically elucidate the function and mechanism of IGF2BP1 in promoting fetal hemoglobin expression in adult hematopoietic stem/progenitor cells. Finally, we discuss the limitations and challenges of IGF2BP1 as a therapeutic target, offering insights into its prospects.

胎盘上 mRNA 结合蛋白 IGF2BP1 属于保守的 RNA 结合蛋白家族。它主要促进 RNA 稳定、调节翻译和 RNA 定位,并通过其下游效应物介导基因表达。大量研究表明,IGF2BP1 在胚胎发生和癌变过程中发挥着至关重要的作用。IGF2BP1 在实体瘤中调控细胞增殖、侵袭和化疗抗性的作用引起了研究人员的关注。此外,一些研究强调了 IGF2BP1 在血液恶性肿瘤和血液遗传疾病中的重要性,并将其定位为治疗血液病的一个有前景的靶点。然而,在血液学领域缺乏有关 IGF2BP1 基因的系统总结。在这篇综述中,我们全面概述了 IGF2BP1 的发现和分子结构,以及最近关于其在胚胎发生中调控作用的研究。我们还重点研究了 IGF2BP1 通过与其靶标 mRNA 相互作用调控血液恶性肿瘤的机制。此外,我们还系统地阐明了 IGF2BP1 在促进成体造血干细胞/祖细胞中胎儿血红蛋白表达方面的功能和机制。最后,我们讨论了 IGF2BP1 作为治疗靶点的局限性和挑战,并对其前景提出了见解。
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引用次数: 0
SOST/Sclerostin impairs the osteogenesis and angiogesis in glucocorticoid-associated osteonecrosis of femoral head. 糖皮质激素相关股骨头坏死中的 SOST/Sclerostin 会损害成骨和血管生成。
IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-28 DOI: 10.1186/s10020-024-00933-5
Junming Huang, Tianle Ma, Chenzhong Wang, Zhe Wang, Xinyuan Wang, Bingxuan Hua, Chang Jiang, Zuoqin Yan

Background: Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) is a progressive bone disorder which frequently results in femoral head collapse and hip joint dysfunction. Sclerostin (SOST) is principally secreted by osteocytes in bone and plays an important role in bone homeostasis and homeostasis of skeletal integrity. Our previous study reported that short-term use of glucocorticoid increased serum sclerostin levels. Here this study is aimed to identify whether sclerostin played an essential role in the occurrence and development of GA-ONFH.

Methods: Glucocorticoid-induced osteonecrosis of femoral head (ARCO stage II) samples were collected and sclerostin staining was conducted. Osteocyte cell line Ocy454, MC3T3-E1 and endothelial cells was used. MC3T3-E1 or endothelial cells were co-cultured with Ocy454 or SOST-silencing Ocy454 in presence of dexamethasone to mimic the crosstalk of various cells in the bone niche. GA-ONFH rat model and SOST knockout model was built to better understand the phenomenon in vivo.

Results: Sclerostin was highly concentrated in osteonecrosis patient sample in the necrotic area. Co-culture with osteocytes aggravated the inhibition of dexamethasone on MC3T3-E1 and endothelial cells. Sclerostin derived from osteocytes impaired osteogenesis and angiogenesis via inhibiting the Wnt pathway. In GA-ONFH rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism compared with the wild type group through histological, immunohistochemical and bone metabolic analyses.

Conclusion: Sclerostin contribute to pathologic process of GA-ONFH by impairing osteogenesis and angiogenesis.

背景:糖皮质激素相关性股骨头坏死(GA-ONFH)是一种进行性骨病,常导致股骨头塌陷和髋关节功能障碍。硬骨素(SOST)主要由骨中的骨细胞分泌,在骨平衡和骨骼完整性平衡中发挥着重要作用。我们之前的研究报道,短期使用糖皮质激素会增加血清硬骨素的水平。本研究旨在确定硬骨素在 GA-ONFH 的发生和发展中是否发挥了重要作用:方法:收集糖皮质激素诱导的股骨头坏死(ARCO II 期)样本并进行硬骨素染色。使用骨细胞系 Ocy454、MC3T3-E1 和内皮细胞。在地塞米松存在下,将 MC3T3-E1 或内皮细胞与 Ocy454 或 SOST 沉默的 Ocy454 共同培养,以模拟骨龛中各种细胞的串扰。为了更好地理解这一现象,我们建立了GA-ONFH大鼠模型和SOST基因敲除模型:结果:骨坏死患者样本中的硬骨素高度集中于坏死区域。与骨细胞共培养可增强地塞米松对 MC3T3-E1 和内皮细胞的抑制作用。从骨细胞中提取的硬骨素通过抑制 Wnt 通路阻碍成骨和血管生成。在 GA-ONFH 大鼠模型中,通过组织学、免疫组化和骨代谢分析,SOST 基因敲除组与野生型组相比,可改善骨坏死的发生率并改善骨代谢:结论:Sclerostin通过影响骨生成和血管生成而导致GA-ONFH的病理过程。
{"title":"SOST/Sclerostin impairs the osteogenesis and angiogesis in glucocorticoid-associated osteonecrosis of femoral head.","authors":"Junming Huang, Tianle Ma, Chenzhong Wang, Zhe Wang, Xinyuan Wang, Bingxuan Hua, Chang Jiang, Zuoqin Yan","doi":"10.1186/s10020-024-00933-5","DOIUrl":"10.1186/s10020-024-00933-5","url":null,"abstract":"<p><strong>Background: </strong>Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) is a progressive bone disorder which frequently results in femoral head collapse and hip joint dysfunction. Sclerostin (SOST) is principally secreted by osteocytes in bone and plays an important role in bone homeostasis and homeostasis of skeletal integrity. Our previous study reported that short-term use of glucocorticoid increased serum sclerostin levels. Here this study is aimed to identify whether sclerostin played an essential role in the occurrence and development of GA-ONFH.</p><p><strong>Methods: </strong>Glucocorticoid-induced osteonecrosis of femoral head (ARCO stage II) samples were collected and sclerostin staining was conducted. Osteocyte cell line Ocy454, MC3T3-E1 and endothelial cells was used. MC3T3-E1 or endothelial cells were co-cultured with Ocy454 or SOST-silencing Ocy454 in presence of dexamethasone to mimic the crosstalk of various cells in the bone niche. GA-ONFH rat model and SOST knockout model was built to better understand the phenomenon in vivo.</p><p><strong>Results: </strong>Sclerostin was highly concentrated in osteonecrosis patient sample in the necrotic area. Co-culture with osteocytes aggravated the inhibition of dexamethasone on MC3T3-E1 and endothelial cells. Sclerostin derived from osteocytes impaired osteogenesis and angiogenesis via inhibiting the Wnt pathway. In GA-ONFH rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism compared with the wild type group through histological, immunohistochemical and bone metabolic analyses.</p><p><strong>Conclusion: </strong>Sclerostin contribute to pathologic process of GA-ONFH by impairing osteogenesis and angiogenesis.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"167"},"PeriodicalIF":6.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Molecular Medicine
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