Journal of Inflammation Research
·
2023
·
IF 4.5
Dongsheng Zhu,Zhitao Zhu,Han Qi
Objective Long non-coding RNA plays an important role in osteogenic differentiation. Nuclear enriched abundant transcript 1 (NEAT1) has been revealed to promote osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs), but the underlying regulatory mechanism remains unknown in acute suppurative osteomyelitis of children.Methods Osteogenic medium (OM) was used to induce osteogenic differentiation. Quantitative real-time PCR and Western blotting were used to evaluate gene expression. The effects of NEAT1, microRNA 339–5p (miR-339-5p), and salmonella pathogenicity island 1 (SPI1) on osteogenic differentiation were assessed in vitro using alizarin red S staining assays and alkaline phosphatase activity. Interactions between NEAT1, miR-339-5p, and SPI1 were identified using immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation.Results During osteogenic differentiation, expression of NEAT1 was up-regulated in hBMSCs, and miR-339-5p level was down during osteogenic differentiation. Knockdown of NEAT1 reduced the osteogenic differentiation of hBMSCs, and down-regulation of miR-339-5p may counteract the effect of NEAT1 silencing. SPI1 was a target of miR-339-5p by luciferase reporter assay and was also a transcription factor of NEAT1 by chromatin immunoprecipitation. A positive NEAT1-miR-339-5p-SPI1 feedback loop was found to be present during osteogenic differentiation in hBMSCs.Conclusion It was the first study to reveal that the NEAT1-miR-339-5p-SPI1 feedback loop can promote osteogenic differentiation in hBMSCs and shed a new light on the role of NEAT1 during osteogenic differentiation.
研究领域:
分子生物学
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细胞生物学
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医学遗传学
·
儿科
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Hongjie Wen,Zhong Chen,Yi Cui,Yongqing Xu
Osteomyelitis is one of the most challenging diseases in the field of orthopedics for its complex pathogenesis and unsatisfactory treatment. The mechanism underlying its occurrence and development is still unclear. In our previous study, we found that long non-coding RNA (lncRNA) NONHSAT009968 inhibited the ability of osteogenic differentiation in staphylococcal protein A (SPA)-treated human bone marrow mesenchymal stem cells (hBMMSCs), but the underlying mechanism remains unclear. The current study was aimed at elucidating the possible mechanism of NONHSAT009968 in regulating osteogenic differentiation and bone defect repairability of hBMMSCs under infection. It was revealed that Wnt3a played a key role in promoting osteogenic differentiation of hBMMSCs treated with SPA in vitro. In addition, NONHSAT009968 inhibited osteogenic differentiation of hBMMSCs treated with SPA via Wnt3a, both in vivo and in vitro. In sum, the results suggested that lncNONHSAT009968 inhibited osteogenic differentiation of hBMMSCs in SA-induced inflammation through Wnt3a, which may have affected the occurrence and development of osteomyelitis. This study might provide novel insights regarding osteomyelitis and infectious bone defects.
研究领域:
骨科
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分子生物学
·
干细胞研究
·
炎症
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DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2023
·
IF 13.1
Hao Zhang,Li Li,Lei Chu,Jing Huang,Xiaochen Chen,Xianglong Zhuo,Yulin Wang,John Robert Honiball,Bin Wang,Wei Chen,William W. Lu,Deping Wang,Bing Li,Xu Cui,Haobo Pan
Effective treatment of osteomyelitis remains to be clinical challenge due to the recurrent and persistent nature of the disease. Studies have shown that borate glasses can serve as implants for local drug delivery in treating osteomyelitis, as well as aid in regenerating bone defects in vivo . However, both the kinetics of drug release from borate glass-based implants and the underlying molecular mechanism for promoting bone regeneration remain unclear. Here, delivery implants with varying amounts of antibiotics were fabricated by encapsulating gentamicin sulfate (GS) into a chitosan glue and applying it to borosilicate glass (BSG). Upon immersion in phosphate buffered saline (PBS), delivery implants degraded and converted into hydroxyapatite (HA). All delivery implants released GS sustainably over a period of around 25 days in both PBS and K2HPO4 solutions and displayed efficacious inhibition of E. coli and S. aureus in vitro. GS release occurred through diffusion for inhibition whereby Fickian diffusion was revealed to be the predominant release kinetic. Ions (B, Ca, P and Si) released from BSG supported the proliferation, differentiation, osteogenic gene expression and protein secretion of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. When implanted in a rabbit tibial osteomyelitis model, osteomyelitis in the experimental group with delivery implants was effectively cured. Meanwhile, delivery implants have significant osteogenesis-promoting effects after implantation time of 12-weeks in vivo . Implantation of BSG-based drug delivery implants developed in this study may provide a promising method for treating osteomyelitis as well as for facilitating efficient bone regeneration.
研究领域:
材料科学
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生物医学工程
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药学
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再生医学
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产品关联
DOI
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2020
·Vol. 68
·期 5
·428-435
·
IF 1.416
Si-qi Wang,Xiao Yang,Yong-gang Zhang,En-bo Cai,Xiao-man Zheng,Yan Zhao,Ge Li,Mei Han,Li-min Yang
Ginseng (G) and Prepared Rehmannia Root (PRR) are commonly used in traditional Chinese medicine for blood supplementation. This study aimed to study G and PRR with different compatibility ratios changes in chemical composition and inhibition of cyclophosphamide-induced myelosuppression. HPLC was used to determine the chemical constituents of 13 ginsenosides, 5-hydroxymethylfurfural (5-HMF) and verbascoside in different proportions of G-PRR. Balb/c mice were injected intraperitoneally with cyclophosphamide (CTX) to induce bone marrow suppression. The effects of different proportions of G-PRR on peripheral blood, bone marrow nucleated cells, thymus and spleen index of myelosuppressed mice were analyzed. The results showed that the compatibility of G and PRR can promote the dissolution of ginsenosides, and the content of conventional ginsenosides decreased, and the content of rare ginsenosides increased. Different proportions of G-PRR increased the number of peripheral blood and bone marrow nucleated cells in cyclophosphamide-induced bone marrow suppression mice (p < 0.01), increased thymus index (p < 0.01), decreased spleen index (p < 0.01). Different proportions of G-PRR can improve the myelosuppression induced by cyclophosphamide in mice, and the combined effect of G-PRR is better than the single decoction of G and PRR. Among them, G-PRR 2 : 3 and G-PRR 1 : 2 were better than the other groups. These results indicate that different proportion of G-PRR can improve bone marrow suppression, and the combined decoction of G-PRR is better than the separate Decoction in improving bone marrow suppression. This improvement may be related to the changes of the substance basis and active ingredients of G-PRR.
研究领域:
药理学
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中医药
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植物化学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Ziao Zhou,Peng Zhang,Dinghao Chen,Nan Kong,Huayang Liu,Juan Liang,Kai Huang,Huaimin Wang
Osteomyelitis poses substantial therapeutic challenges due to the prevalence of multidrug-resistant bacterial infections and associated inflammation. Current treatment regimens often rely on a combination of corticosteroids and antibiotics, which can lead to complications and impede effective bacterial clearance. In this study, we present CADP-10, a Cecropin A-derived peptide, designed to target methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli (MRE), while simultaneously addressing inflammatory responses. CADP-10 self-assembles into nanobacterial net (NBacN) that selectively identify and bind to bacterial endotoxins (LPS and LTA), disrupting membrane integrity and depolarizing membrane potential, which culminates in bacterial death. Importantly, these NBacN are bound to LPS and LTA from dead bacteria, preventing their engagement with TLR receptors and effectively blocking downstream inflammatory pathways. Our assessments of CADP-10 demonstrate good biosafety in both in vitro and in vivo models. Notably, in a rabbit osteomyelitis model, CADP-10 eliminated MRSA-induced bone infections, mitigated inflammation, and promoted bone tissue regeneration. This research highlights the potential of CADP-10 as a multifunctional antimicrobial agent for the management of infectious inflammatory diseases.
研究领域:
微生物学
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感染病学
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药理学
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产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2025
·Vol. 10
·期 1
·1-19
·
IF 52.7
Wang Baile,Liu Jie,Wang Qin,Arhatte Malika,Cheong Lai Yee,Glogowska Edyta,Jiang Xue,Chung Sookja Kim,Jin Leigang,Hu Qianxing,Wang Yu,Honoré Eric,Xu Aimin
With aging or osteoporosis, bone marrow adipogenesis is increased and inversely correlates with the loss of bone mass. Bone marrow adipocytes are derived from multipotent bone marrow mesenchymal stem cells (BMMSCs), which can differentiate into either fat or bone. BMMSCs are mechanosensitive cells, but how mechanical loading is implicated in the in vivo regulation of bone marrow adipogenesis and its impact on bone remodeling remain poorly understood. Here, we identify the mechanosensitive cationic channel Piezo1 in BMMSCs as a key suppressor of bone marrow adipogenesis by preventing local inflammation, thereby enhancing osteoblast differentiation and bone formation. Mice with a specific Piezo1 invalidation in BMMSCs exhibit osteoporosis and marrow adiposity, together with resistance to the beneficial effects of exercise on bone health. Accordingly, Piezo1-deficient BMMSCs in vitro preferentially differentiate into adipocytes rather than osteoblasts. Invalidation of Piezo1 in BMMSCs enhances the autocrine activation of CCR2 by Ccl2, which further induces lipocalin-2 (Lcn2) production via NF-κB activation, thereby promoting adipocyte differentiation. Conversely, Piezo1 opening induces Klf2 expression through CaMKII, preventing c-Jun activation, Ccl2 production and bone marrow adipogenesis. These findings demonstrate that Piezo1 activation in BMMSCs suppresses bone marrow adipogenesis to maintain bone strength by preventing the Ccl2-Lcn2 inflammatory autocrine loop, thus uncovering a previously unrecognized link between mechanotransduction, inflammation, and cell fate determination.
研究领域:
骨生物学
·
干细胞生物学
·
机械转导
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炎症与免疫
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代谢性骨病
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分子细胞生物学
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yanzhi Zhao,Weixian Hu,Shengming Zhang,Yuheng Liao,Kangkang Zha,Chenyan Yu,Zhenhe Zhang,Wenqian Zhang,Bobin Mi,Faqi Cao,Guohui Liu,Wu Zhou
Impaired fracture healing in diabetic patients poses a persistent clinical challenge, with underlying mechanisms that remain to be fully elucidated. These findings reveal that high glucose microenvironments generate excessive reactive oxygen species in bone marrow mesenchymal stem cells (BMSCs) and bone marrow-derived macrophages (BMDMs), leading to mitochondrial dysfunction and metabolic impairment. These pathophysiological disruptions suppress osteogenic differentiation in BMSCs while driving pro-inflammatory polarization in BMDMs, processes closely tied to high-glucose-induced inhibition of Adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation. Restoration of AMPK phosphorylation emerges as a pivotal strategy to mitigate oxidative stress and restore cellular function. To address this, a dual-targeted therapeutic system (DLNPs@HA hydrogel) is developed that combines anti-CD105-antibody-modified nanoliposomes and phosphatidylserine-modified nanoliposomes, both encapsulating the specific AMPK activator α-lipoic acid. This hydrogel facilitates sustained nanoparticle release, enabling precise and effective delivery to BMSCs and BMDMs. In vitro, DLNPs@HA hydrogel successfully enhances osteogenic activity and suppresses inflammatory responses. In vivo, it accelerates fracture healing in diabetic mice. By precisely targeting BMSCs and BMDMs and reversing bicellular oxidative stress, this integrative medical-engineering strategy provides a promising and translatable solution for diabetic fracture repair, seamlessly bridging mechanistic insights with therapeutic innovation.
研究领域:
生物医学工程
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内分泌学
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创伤骨科
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细胞生物学
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产品关联
DOI
高影响因子
Lipids in Health and Disease
·
2024
·Vol. 23
·期 1
·1-11
·
IF 3.9
Li Jinying,Chen Yongshao,Zha Dingsheng,Wu Chunhui,Li Xiaofen,Yang Li,Cao Hui,Cai Shexing,Cai Yuebo
The accumulation of reactive oxygen species (ROS) within the bone marrow microenvironment leads to diminished osteogenic differentiation and heightened lipogenic differentiation of mesenchymal stem cells residing in the bone marrow, ultimately playing a role in the development of osteoporosis (OP). Mitigating ROS levels is a promising approach to counteracting OP. In this study, a nanozyme composed of magnesium-based zeolitic imidazolate frameworks (Mg-ZIF) was engineered to effectively scavenge ROS and alleviate OP. The results of this study indicate that Mg-ZIF exhibits significant potential in scavenging ROS and effectively promoting osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Additionally, Mg-ZIF was found to inhibit the differentiation of BMSCs into adipose cells. In vivo experiments further confirmed the ability of Mg-ZIF to mitigate OP by reducing ROS levels. Mechanistically, Mg-ZIF enhances the differentiation of BMSCs into osteoblasts by upregulating lipid metabolic pathways through ROS scavenging. The results indicate that Mg-ZIF has potential as an effective therapeutic approach for the treatment of osteoporosis.
研究领域:
生物材料
·
干细胞生物学
·
骨代谢
·
活性氧
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-16
·
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
·
医学
·
老年病学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bone Research
·
2025
·Vol. 13
·期 1
·1-17
·
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
·
骨骼学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Kai Lv,Zhen Wang,Wenjun He,Zijing Feng,Hui Xing,Yuanfang Jiang,Yingtong Lu,Jingjie Shang,Bin Guo,Hao Xu,Guowei Li,Bo Ning,Dong Ma
Nitric oxide (NO) as a promising therapeutic molecule for infection treatments is impeded by challenges of precise delivery and accumulation in treating deep tissue infections, such as osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). Herein, a bacterial-targeting liposome (MN@Mal-Lips) assembled by maltotriose (Mal)-modified cholesterol and lecithin was presented for synergistic NO/methicillin (MET) therapy of MRSA-infected osteomyelitis. MN@Mal-Lips were specifically internalized by MRSA via Mal transporters and thus targetedly accumulated at deep MRSA-infected site. Attributed to the capabilities of NO to induce biofilm dispersal and reverse bacterial resistance, the precisely delivered NO combined with MET facilitating efficient bacterial eradication by disrupting bacterial cell membrane and damaging bacterial DNA. Furthermore, MN@Mal-Lips relieved the local inflammation by potentiating the polarization of macrophages to M2-type while suppressing the M1-type. Meanwhile, MN@Mal-Lips promoted the proliferation, migration, and mineralization of osteoblast, as well as upregulated osteogenesis-related genes, thus repairing the bone tissue. Together, this bacterial-targeting NO-delivery liposome system offers an effective therapeutic strategy for clinical management of MRSA-induced osteomyelitis and may provide great possibilities in the development of NO therapy combating with deep tissue infections caused by drug-resistant bacteria.
研究领域:
药学
·
微生物学
·
医学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2021
·Vol. 33
·期 41
·2102926
·
IF 30.849
Jieni Fu,Yuan Li,Yu Zhang,Yanqin Liang,Yufeng Zheng,Zhaoyang Li,Shengli Zhu,Changyi Li,Zhenduo Cui,Shuilin Wu
Preventing deep bacterial infection and simultaneously enhancing osteogenic differentiation are in great demand for osteomyelitis. Microwave (MW) dynamic therapy is attracting attention due to its excellent penetration ability, but the mechanism of MW-induced reactive oxygen species (ROS) is still unknown. Herein, MW-responsive engineered pseudo-macrophages (M-Fe 3 O 4 /Au nanoparticles (NPs)) are fabricated to clear Staphylococcus aureus infections and induce M2 polarization of macrophages to improve osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) under MW irradiation. Fe 3 O 4 /Au NPs can generate · O 2 − and heat under MW irradiation in a saline solution, and the mechanism is put forward via finite element modeling and density functional theory calculations. Due to the gap plasmon, electromagnetic hotspots are produced at Fe 3 O 4 –Au interface at 2.45 GHz. Because of these induced electromagnetic hotspots, the sodium species is field-ionized and subsequently reacts with oxygen to produce · O 2 − . Meanwhile, the Fe 3 O 4 /Au NPs have a stronger ability than Fe 3 O 4 NPs to fix oxygen, favoring the production of ROS. Additionally, MW-treated macrophages diminish to secrete inflammatory cytokines, resulting in the decrease of ROS production in MSCs and thus enhancing their osteogenic differentiation. These engineered pseudo-macrophages will be promising for effectively treating bacterial infections and promoting osteoblast differentiation simultaneously in deep tissues under MW irradiation.
研究领域:
生物医学工程
·
纳米技术
·
传染病
·
组织工程
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）