International Journal of Nanomedicine
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2023
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IF 8
Wenshu Cheng,Xinyue Xu,Yuanyuan Lang,Zugen Cheng,Mohammad Rizwan,Xiaomin Tang,Lixin Xie,Yanling Liu,Hengyi Xu,Yang Liu
Purpose To evaluate the effects of anatase and rutile TiO2 nanoparticles (NPs) on the growth and development of bones in young rats and explore their possible mechanisms.Methods Three-week-old male rats were orally administered anatase TiO2 NPs and rutile TiO2 NPs for 28 days. The indicators of rat growth and development, liver function, bone metabolism, and insulin-like growth factor-1 (IGF-1) levels were evaluated. Micro-computed tomography (micro-CT) and immunohistochemistry were used to evaluate the tibia.Results No significant differences were observed among growth and development indicators in young rats. Significant differences were found in IGF-1 levels, phosphorus levels, and liver function. Micro-CT revealed osteoporosis in the bones. The micro-CT data supported the same result. Bone immunohistochemistry results showed that the expression of osteoprotegerin (OPG) was decreased and the expression of receptor activator of nuclear factor-κB ligand (RANKL) and cathepsin K (CTSK) was increased.Conclusion This study demonstrated that TiO2 NPs can damage bones via the IGF-1/OPG/RANKL/CTSK pathway in young rats. Furthermore, rutile TiO2 NPs damaged the bones more seriously than anatase TiO2 NPs.
研究领域:
纳米技术
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生物材料
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骨骼生物学
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毒理学
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DOI
PubMed
高影响因子
JBMR Plus
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2022
·Vol. 7
·期 1
·e10706
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IF 0
Wenhuan Chai,Weiwei Hao,Jintao Liu,Zhenglin Han,Shiyu Chang,Liben Cheng,Mingxin Sun,Guofang Yan,Zemin Liu,Yin Liu,Guodong Zhang,Li Xing,Hongqian Chen,Peng Liu
The Cre/lox system is a fundamental tool for functional genomic studies, and a number of Cre lines have been generated to target genes of interest spatially and temporally in defined cells or tissues; this approach has greatly expanded our knowledge of gene functions. However, the limitations of this system have recently been recognized, and we must address the challenge of so-called nonspecific/off-target effects when a Cre line is utilized to investigate a gene of interest. For example, cathepsin K (Ctsk) has been used as a specific osteoclast marker, and Cre driven by its promoter is widely utilized for osteoclast investigations. However, Ctsk-Cre expression has recently been identified in other cell types, such as osteocytes, periosteal stem cells, and tenocytes. To better understand Ctsk-Cre expression and ensure appropriate use of this Cre line, we performed a comprehensive analysis of Ctsk-Cre expression at the single-cell level in major organs and tissues using two green fluorescent protein (GFP) reporters (ROSA nT-nG and ROSA tdT) and a tissue clearing technique in young and aging mice. The expression profile was further verified by immunofluorescence staining and droplet digital RT-PCR. The results demonstrate that Ctsk-Cre is expressed not only in osteoclasts but also at various levels in osteoblast lineage cells and other major organs/tissues, particularly in the brain, kidney, pancreas, and blood vessels. Furthermore, Ctsk-Cre expression increases markedly in the bone marrow, skeletal muscle, and intervertebral discs in aging mice. These data will be valuable for accurately interpreting data obtained from in vivo studies using Ctsk-Cre mice to avoid potentially misleading conclusions. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. Graphical We performed a comprehensive analysis of Ctsk-Cre expression at the single-cell level in major organs and tissues using two GFP reporters. These results demonstrate that Ctsk-Cre is expressed not only in osteoclasts but also at various levels in osteoblast lineage cells and other major organs/tissues, particularly in the brain, kidney, pancreas, and blood vessels. These data will be valuable for accurately interpreting data to avoid potentially misleading conclusions.
研究领域:
遗传学
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分子生物学
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细胞生物学
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骨骼与矿物质研究
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PubMed
BIOCHEMICAL PHARMACOLOGY
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2022
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IF 6.1
Yanbei Tu,Lihua Tan,Tao Lu,Kai Wang,Haiyong Wang,Bing Han,Yuxin Zhao,Hanbin Chen,Yanfang Li,Haixia Chen,Meiwan Chen,Chengwei He
The roots of Glycine tabacina are used to treat rheumatoid arthritis (RA) and joint infection in folk medicine. Glytabastan B (GlyB), a newly reported coumestan isolated from this species, was found to significantly attenuate IL-1β-induced inflammation in SW982 human synovial cells at 3 and 6 μM, as evidenced by the decreased levels of pro-inflammatory mediators and matrix metalloproteinases (MMPs). GlyB also suppressed RANKL-induced osteoclastogenesis, decreased the expression of osteoclastogenic markers (NFATc1, CTSK , MMP-9) and osteoclast-mediated bone resorption. Further, GlyB administration (12.5 and 25 mg/kg) significantly inhibited inflammation, osteoclast formation and disease progression in collagen-induced arthritis (CIA) mice. Integration of network pharmacology , quantitative phosphoproteomic and experimental pharmacology results revealed that these beneficial actions were closely associated with the blockade of GlyB on the activation of MAPK , PI3K/AKT and their downstream signals including NF-κB and GSK3β/NFATc1. Drug affinity responsive target stability (DARTS) assay, cellular thermal shift (CETSA) assay and molecular docking analysis confirmed that there were direct interactions between GlyB and its target proteins ERK2 , JNK1 and class Ⅰ PI3K catalytic subunit p110 (α, β, δ and γ), which significantly contributed to the inhibition of activation of MAPK and PI3K/AKT pathways. In conclusion, these results strongly suggest GlyB is a promising multiple-target candidate for the development of agents for the prevention and treatment of RA.
研究领域:
药理学
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免疫学
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风湿病学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）