Advanced Science
·
2025
·
IF 14.1
Yiwen Zhou,Lili Chen,Miaomiao Han,Peixiang Zhu,Yanyi Wang,Xuanxuan Yu,Tingyu Reng,Huijuan Wang,Baochao Li,Caixia Zhang,Ziwei Huang,Shuang Lin,Guoyun Wang,Jie Ge,Baosheng Guo,Huang Li
Maxillary underdevelopment is a critical component of skeletal Class III malocclusion, closely linked to altered biomechanical signaling. Mechanical stimulation through early facemask protraction can effectively promote maxillary growth, yet the underlying mechanotransduction mechanisms remain unclear. In this study, fibroblast growth factor 9 (FGF9) is identified as a key biomechanical responder in maxillary development. Secreted predominantly by osteocytes, FGF9 interacts with fibroblast growth factor receptor 2 (FGFR2) on preosteoblasts to inhibit osteogenic differentiation. Mechanical stress reduces FGF9 secretion from osteocytes, thereby relieving its inhibitory effect and enhancing osteogenesis. Mechanistically, FGF9 promotes nuclear translocation of FGFR2 in preosteoblasts, which modulates transcription factors ATF5 and NR2F1 to suppress bone formation. In vivo, targeted overexpression of FGF9 in bone tissue led to significant maxillary growth impairment, underlying the pathological impact of disrupted mechanical signaling. These findings reveal a novel osteocyte–preosteoblast axis regulated by FGF9–FGFR2 signaling in response to mechanical stimulation and provide mechanistic insight into how biomechanical forces shape craniofacial development. This pathway offers new mechanistic insights and potential therapeutic targets for correcting craniofacial skeletal abnormalities.
研究领域:
发育生物学
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分子生物学
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生物力学
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颅面遗传学
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骨生物学
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2021
·
IF 4.06
Xu Xiao,Xiaolei Hou,Wenda Shi,Chanchan Hu,Yanan Cui,Jiuli Hu,Zongfang Piao,Xiaoqin Zhu,Qingshan Li,Fan Xu
Objective: Oxymatrine has shown strong anti-cancer ability, but its mechanism is not well-studied. Methods: The inhibitory rates of oxymatrine with various concentrations (0, 1, 2, 4, 6, 8, 16, 32 mg/ml) on MCF-7 cells were detected by CCK-8. The effects of oxymatrine on the expression of miRNA-140-5P in MCF-7 cells were detected by real-time fluorescent quantitative PCR (RT-PCR). miRNA-140-5P mimics or NC mimics were transfected into cells using Lipofectamine 2000. Eventually, the cells were divided into control-group, drug-group, miRNA-140-5P mimics group, NC mimics group, and miRNA-140-5P mimics + drug group. Cell viability was detected by CCK-8 assay and apoptosis rate of each group were measured by using Flow cytometry. Western blot was carried out to detect the protein expression of TGFBR1 and FGF9. Results: Oxymatrine at various concentrations had conspicuous inhibitory effect on the proliferation of MCF-7 cells ( P<0.05 ), and the inhibitory effect of oxymatrine on MCF-7 cells showed both dose- and time-dependent manners. The relative expression of miRNA-140-5P in MCF cells was remarkably lower than that in MCF-10A. Oxymatrine could effectively promote the expression of miRNA-140-5P in MCF-7 cells, and the relative expression of miRNA-140-5P increased significantly with the increased dose of oxymatrine ( P<0.05 ). Both transfection of miRNA-140-5P mimics and oxymatrine treatment could reduce the proliferation of MCF-7 cells ( P<0.05 ), and the proliferation of cells in miRNA-140-5P mimics + drug-group was significantly lower than that of other groups ( P<0.05 ). Compared with the control-group, the protein expressions of TGFbR1 and FGF9 in low-dose, medium-dose and high-dose groups were dramatically decreased ( P<0.05 ), in a dose-dependent manner ( P<0.05 ). Conclusion: Oxymatrine inhibits proliferation and promotes cell apoptosis of breast cancer MCF-7 cells. The mechanism may contribute to the regulation of miRNA-140-5p and its target genes.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Genes
·
2023
·Vol. 14
·期 5
·1106
·
IF 3.5
Qi Jia,Shuangshuang Zhang,Dan Wang,Jianqiang Liu,Xinhui Luo,Yu Liu,Xin Li,Fuliang Sun,Guangjun Xia,Lichun Zhang
Fibroblast growth factor 9 (FGF9) is crucial for the growth and development of hair follicles (HFs); however, its role in sheep wool growth is unknown. Here, we clarified the role ofFGF9in HF growth in the small-tailed Han sheep by quantifyingFGF9expression in skin tissue sections collected at different periods. Moreover, we evaluated the effects ofFGF9protein supplementation on hair shaft growth in vitro andFGF9knockdown on cultured dermal papilla cells (DPCs). The relationship betweenFGF9and the Wnt/β-catenin signaling pathway was examined, and the underlying mechanisms ofFGF9-mediated DPC proliferation were investigated. The results show thatFGF9expression varies throughout the HF cycle and participates in wool growth. The proliferation rate and cell cycle ofFGF9-treated DPCs substantially increase compared to that of the control group, and the mRNA and protein expression ofCTNNB1, a Wnt/β-catenin signaling pathway marker gene, is considerably lower than that in the control group. The opposite occurs inFGF9-knockdown DPCs. Moreover, other signaling pathways are enriched in theFGF9-treated group. In conclusion,FGF9accelerates the proliferation and cell cycle of DPCs and may regulate HF growth and development through the Wnt/β-catenin signaling pathway.Keywords:fibroblast growth factor 9;small-tailed Han sheep;dermal papilla cells;proliferation
研究领域:
动物科学
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分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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