CELLULAR SIGNALLING
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2025
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IF 3.7
Yuyan Sun,Ziyu Luo,Haiqi Zhou,Sha Wu,Hongwei Shen,Yuanyuan Fu,Thai Namanh Ngo,Wen Wang,Yuanrong Wang,Ying Kong
Chondrocyte mechanotransduction dysfunction is a key feature of osteoarthritis (OA). Previous studies have demonstrated that primary cilia play a crucial role in chondrocyte mechanosensation and signal transduction. Transient Receptor Potential Vanilloid 4(TRPV4), which is highly expressed on primary cilia, is a critical mechanotransduction protein and one of the most important Ca 2+ channels. However, the interplay between the mechanism of primary cilia-mediated signaling and that of TRPV4 channel regulation remains poorly understood. Here, we demonstrate that OA chondrocytes and Intraflagellar Transport Protein 88(Ift88) conditional knockout (cKO) mice exhibit reduced ciliary incidence. This results in cartilage degeneration. TRPV4 expression inversely correlated with ciliary integrity, increasing as cilia were lost. In cilia-intact healthy chondrocytes, TRPV4 antagonism inhibited Ca 2+ -dependent NF-κB activation while promoting type II collagen(COL2) synthesis. These effects were abolished by Interleukin-1 beta(IL-1β)-induced ciliary defect or IFT88 deficiency. Chromatin immunoprecipitation(ChIP) analysis revealed disrupted p65 binding to the COL2 promoter upon the loss of ciliary integrity. Crucially, Ift88 cKO chondrocytes showed unresponsive of the TRPV4 channel, as confirmed by Ca 2+ flux and changes in the expression levels of NF-κB and COL2. Our findings position primary cilia as indispensable regulators of TRPV4-mediated NF-κB - COL2 signaling, offering mechanistic insights into OA pathogenesis and identifying IFT88 as a therapeutic checkpoint.
研究领域:
分子生物学
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细胞生物学
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骨关节炎病理学
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信号转导
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转化医学
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软骨生物学
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机械生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Aoyu Fan,Yunyan Zhang,Yunpeng Li,Wei Meng,Fan Wu,Wei Pan,Zhongliang Ma,Wei Chen
Prostate cancer (PCa) is one of the most common malignancies for male individuals globally. Androgen deprivation therapy (ADT) initially demonstrated significant efficacy in treating PCa; however, most cases of PCa eventually progress to castration-resistant prostate cancer (CRPC), which becomes increasingly challenging to manage. Notably, the loss or disruption of primary cilia in PCa cells may play a critical role in the progression of the disease, and there are no reports on the role of circular RNAs in ciliogenesis. Thus, this warrants further investigation.In this study, key circular RNAs linked to prostate cancer progression, and enzalutamide resistance is identified. Specifically, it is found that hsa_circ_0005185 interacts with OTUB1 and RAB8A, serving as a molecular scaffold. Hsa_circ_0005185 mediates the binding of the deubiquitinase OTUB1 to RAB8A, resulting in the deubiquitination of RAB8A. Consequently, the stable expression of RAB8A promotes the regeneration of primary cilia and enhances the production of GLI3R, an inhibitory factor in the Hedgehog signaling pathway, thereby suppressing AR activity and slowing the progression of CRPC.
研究领域:
肿瘤学
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分子生物学
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癌症遗传学
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信号转导
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2021
·
IF 6.684
Li Jiawei,Sun Ziying,Lv Zhongyang,Jiang Huiming,Liu Anlong,Wang Maochun,Tan Guihua,Guo Hu,Sun Heng,Wu Rui,Xu Xingquan,Yan Wenjin,Jiang Qing,Ikegawa Shiro,Shi Dongquan
Mesenchymal stem cells (MSCs) are well known for their multi-directional differentiation potential and are widely applied in cartilage and bone disease. Synovial mesenchymal stem cells (SMSCs) exhibit a high proliferation rate, low immunogenicity, and greater chondrogenic differentiation potential. Microtubule (MT) plays a key role in various cellular processes. Perturbation of MT stability and their associated proteins is an underlying cause for diseases. Little is known about the role of MT stabilization in the differentiation and homeostasis of SMSCs. In this study, we demonstrated that MT stabilization via docetaxel treatment had a significant effect on enhancing the chondrogenic differentiation of SMSCs. MT stabilization inhibited the expression of Yes-associated proteins (YAP) and the formation of primary cilia in SMSCs to drive chondrogenesis. This finding suggested that MT stabilization might be a promising therapeutic target of cartilage regeneration.
研究领域:
干细胞生物学
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骨科
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2023
·
IF 3.3
Tianqi Huang,Jinglou Chen,Yumiao Zhang,Yao Chen,Congyue Xu,Jing Guo,Hao Ming
Cadmium (Cd) is a toxic heavy metal pollutant and serves as an important environmental endocrine-disrupting chemical. Cd exposure is believed to can enhance the risks of age-related disorders including benign prostatic hyperplasia (BPH). This study was to investigate the harms of Cd exposure on mice prostate and human nonmalignant prostate epithelial RWPE-1 cells. Mice prostate fibrosis was evaluated by visualizing the prostatic collagen deposition via Masson and Sirius red staining, and detecting the content of hydroxyproline. Additionally, the epithelial-mesenchymal transition (EMT), primary ciliogenesis and SHH signaling pathways in both mice prostate and RWPE-1 cells were evaluated. It was found that Cd exposure stimulated prostatic collagen deposition, EMT and primary ciliogenesis, as well as enhanced the circ_0027470 level and reduced the miRNA-1236-3p level. Circ_0027470 functioned as a sponge of miRNA-1236-3p, which had the inhibiting target of SHH. The whole results showed that circ_0027470 promoted Cd exposure-induced prostatic fibrosis via sponging miRNA-1236-3p and subsequently stimulating SHH signaling pathway. This study shed a light on a novel molecular mechanism involved in circRNA for Cd exposure-induced prostate deficits.
研究领域:
毒理学
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分子生物学
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细胞生物学
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环境健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL
·
2022
·
IF 66.85
Shu-Hsien Sheu,Srigokul Upadhyayula,Vincent Dupuy,Song Pang,Fei Deng,Jinxia Wan,Deepika Walpita,H. Amalia Pasolli,Justin Houser,Silvia Sanchez-Martinez,Sebastian E. Brauchi,Sambashiva Banala,Melanie Freeman,C. Shan Xu,Tom Kirchhausen,Harald F. Hess,Luke Lavis,Yulong Li,Séverine Chaumont-Dubel,David E. Clapham
Summary Chemical synapses between axons and dendrites mediate neuronal intercellular communication. Here, we describe a synapse between axons and primary cilia: the axo-ciliary synapse. Using enhanced focused ion beam-scanning electron microscopy on samples with optimally preserved ultrastructure, we discovered synapses between brainstem serotonergic axons and the primary cilia of hippocampal CA1 pyramidal neurons. Functionally, these cilia are enriched in a ciliary-restricted serotonin receptor, the 5-hydroxytryptamine receptor 6 (5-HTR6). Using a cilia-targeted serotonin sensor, we show that opto- and chemogenetic stimulation of serotonergic axons releases serotonin onto cilia. Ciliary 5-HTR6 stimulation activates a non-canonical G αq/11 -RhoA pathway, which modulates nuclear actin and increases histone acetylation and chromatin accessibility. Ablation of this pathway reduces chromatin accessibility in CA1 pyramidal neurons. As a signaling apparatus with proximity to the nucleus, axo-ciliary synapses short circuit neurotransmission to alter the postsynaptic neuron’s epigenetic state.
研究领域:
神经科学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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