Bone Research
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2025
·Vol. 13
·期 1
·1-17
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IF 15
Ni Yuehan,Wu Jiamiao,Liu Fengqi,Yi Yating,Meng Xiangjiao,Gao Xiang,Xiao Luyi,Zhou Weiwei,Chen Zexi,Chu Peng,Xing Dan,Yuan Ye,Ding Donghui,Shen Ge,Yang Min,Wu Ronjie,Wang Ling,Melo Luiza Martins Nascentes,Lin Sien,Cheng Xiaoguang,Li Gang,Tasdogan Alpaslan,Ubellacker Jessalyn M.,Zhao Hu,Fang Shentong,Shen Bo
Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional (3D) architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions. Deciphering the spatial interaction of leptin receptor-expressing (LepR + ) stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue. In this study, we introduce an optimized protocol for the 3D analysis of skeletal tissues, enabling the visualization of hematopoietic and stromal cells, especially LepR + stromal cells, within optically cleared bone hemisections. Our method preserves the 3D tissue architecture and is extendable to other hematopoietic sites such as calvaria and vertebrae. The protocol entails tissue fixation, decalcification, and cryosectioning to reveal the marrow cavity. Completed within approximately 12 days, this process yields highly transparent tissues that maintain genetically encoded or antibody-stained fluorescent signals. The bone hemisections are compatible with diverse antibody labeling strategies. Confocal microscopy of these transparent samples allows for qualitative and quantitative image analysis using Aivia or Bitplane Imaris software, assessing a spectrum of parameters. With proper storage, the fluorescent signal in the stained and cleared bone hemisections remains intact for at least 2–3 months. This protocol is robust, straightforward to implement, and highly reproducible, offering a valuable tool for tissue architecture and cellular interaction studies.
研究领域:
细胞生物学
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骨骼学
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DOI
PubMed
高影响因子
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
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2024
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IF 3.9
Zhou Y.-Y.,Zhao S.-Y.,Huang F.-J.,Zhang L.-J.,Liu Y.-L.,Wang J.,Ma X.-J.
Background and purpose Subclinical hypothyroidism (SCH) has been identified to be associated with implantation failure, in which the dysfunction of trophoblast cells is involved. In this study, the transcriptomics of aborted placenta from SCH rats were analyzed. Jupiter microtubule-associated homolog 2 (JPT2) was downregulated in the aborted placenta. This study aims to investigate its role in SCH-associated miscarriage. Methods Spontaneous abortion was observed in SCH rats generated by thyroidectomy combined with levothyroxine administration. The transcriptomics analysis was performed using aborted placenta. Afterward, the effects of JPT2 on trophoblast cells were explored using gain-and loss-of-function experiments. Results Transcriptomics analysis showed 1286 downregulated genes and 2300 upregulated genes in the aborted placenta, and JPT2 was significantly downregulated in the aborted placenta from SCH rats. Afterward, gain-and loss-of-function experiments exhibited that overexpression of JPT2 promoted the proliferation, migration, invasion, spheroid formation of HTR-8/SVneo trophoblast cells and their attachment to endometrial stromal cells, while these biological behaviors were suppressed by JPT2 knockdown. Furthermore, JPT2 accelerated the transcription of leptin receptor (LEPR), and activated signal transducer and activator of transcription 3 (STAT3) signal in a transcription factor AP-2γ-dependent manner. In addition, silencing of LEPR abolished the role of JPT2. Conclusion Our results revealed that JPT2, which was downregulated in the aborted placenta from SCH rats, promoted proliferation, migration, invasion, spheroid formation, and attachment of trophoblast cells via regulating LEPR/STAT3 axis as a transcription co-factor. It is indicated that low expression of JPT2 may contribute to the abortion in individuals with SCH.
研究领域:
内分泌学
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生殖生物学
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分子生物学
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转录组学
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DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-16
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IF 15.7
Li Ke,Hu Sihan,Li Hanwen,Lin Wenzheng,Zhao Duoyi,Xu Zhuobin,Pan Chun,Wang Huihui,Li Dandan,Liu Jingjing,Chen Hao
Resident leptin-receptor-expressing (LepR + ) cells senescence in the aged bone marrow impairs the regenerative capacity of osteo- and other lineages of cells. In this study, a LepR + cell-targeting nitric oxide (NO) nanopump with in vivo self-controlled turn-on ability was constructed to rejuvenate the LepR + cells in the aged bone marrow. The nanopump co-entrapped hydrophobic chemiluminescence substrate and NO donor into the matrix of amphiphilic polymer through a nanoprecipitation process. The chemiluminescence substrate in the NO nanopump automatically reacts with the accumulated H 2 O 2 in the aged bone marrow and then directly transfers the chemical energy to the NO donor to induce in situ NO release. The NO produced in situ within the aged bone marrow triggered the regeneration of the osteoblastic and the other niches in vivo through activating the glycolysis signaling in the senescent LepR + cells. Conclusively, the constructed NO nanopump is a promising tool to counter aging-induced bone marrow disorders.
研究领域:
生物学
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医学
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老年病学
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生物材料
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DOI
PubMed
高影响因子
Frontiers in Genetics
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2022
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IF 4.772
Liqin Yang,Zhixiong Xia,Jianhua Feng,Menghuan Zhang,Pu Miao,Yingjie Nie,Xiangyan Zhang,Zijian Hao,Ronggui Hu
Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder with the underlying etiology yet incompletely understood and no cure treatment. Patients of fragile X syndrome (FXS) also manifest symptoms, e.g. deficits in social behaviors, that are core traits with ASD. Several studies demonstrated that a mutual defect in retinoic acid (RA) signaling was observed in FXS and ASD. However, it is still unknown whether RA replenishment could pose a positive effect on autistic-like behaviors in FXS. Herein, we found that RA signaling was indeed down-regulated when the expression of FMR1 was impaired in SH-SY5Y cells. Furthermore, RA supplementation rescued the atypical social novelty behavior, but failed to alleviate the defects in sociability behavior or hyperactivity, in Fmr1 knock-out (KO) mouse model. The repetitive behavior and motor coordination appeared to be normal. The RNA sequencing results of the prefrontal cortex in Fmr1 KO mice indicated that deregulated expression of Foxp2, Tnfsf10, Lepr and other neuronal genes was restored to normal after RA treatment. Gene ontology terms of metabolic processes, extracellular matrix organization and behavioral pathways were enriched. Our findings provided a potential therapeutic intervention for social novelty defects in FXS.
研究领域:
神经科学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
Food & Function
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2023
·Vol. 14
·期 10
·4807-4823
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IF 6.1
Suwen Liu,Wenhong Jiang,Chang Liu,Shuo Guo,Hao Wang,Xuedong Chang
Chinese chestnut shell is a by-product of chestnut food processing and is rich in polyphenols. This study sought to investigate the effect of chestnut shell polyphenol extract (CSP) on weight loss and lipid reduction in a 12-week high-fat diet (HFD)-induced murine obesity model. CSP (300 mg per kg body weight) was administered intragastrically daily. AG490, a JAK2 protein tyrosine kinase inhibitor, was also intraperitoneally injected. The results showed that an HFD induced leptin resistance (LR). Compared to corresponding values in the HFD group, CSP treatment improved blood lipid levels, weight, and leptin levels in obese mice (p < 0.01). Additionally, CSP treatment enhanced enzyme activity by improving total antioxidant capacity, attenuating oxidative stress, and reducing fat droplet accumulation and inflammation in the liver, epididymal, and retroperitoneal adipose tissue. CSP also activated the LEPR-JAK2/STAT3-PTP1B-SOCS-3 signal transduction pathway in hypothalamus tissue and improved LR while regulating the expression of proteins related to lipid metabolism (PPARγ, FAS, and LPL) in white adipose tissue in the retroperitoneal cavity. However, the amelioration of lipid metabolism by CSP was dependent on JAK2. Molecular docking simulation further demonstrated the strong binding affinity of procyanidin C1 (−10.3983297 kcal mol−1) and procyanidin B1 (−9.12686729 kcal mol−1) to the crystal structure of JAK2. These results suggest that CSP may be used to reduce HFD-induced obesity with potential application as a functional food additive.
研究领域:
营养学
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药理学
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分子生物学
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肥胖研究
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DOI
PubMed
高影响因子
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