Cell Metabolism
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2022
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IF 31.373
Ke Lu,Tian-Shu Shi,Si-Yu Shen,Yong Shi,Hong-Liang Gao,Jing Wu,Xiang Lu,Xiang Gao,Huang-xian Ju,Wei Wang,Yi Cao,Di Chen,Chao-Jun Li,Bin Xue,Qing Jiang
Summary Hepatic osteodystrophy (HOD) is a metabolic bone disease that is often associated with chronic liver disease and is marked by bone loss. Here, we demonstrate that hepatic expression of the phosphatase PP2Acα is upregulated during HOD, leading to the downregulation of expression of the hepatokine lecithin-cholesterol acyltransferase (LCAT). Loss of LCAT function markedly exacerbates the bone loss phenotype of HOD in mice. In addition, we found that alterations in cholesterol levels are involved in the regulation of osteoblast and osteoclast activities. We also found that LCAT improves liver function and relieves liver fibrosis in the mouse HOD model by promoting reversal of cholesterol transport from the bone to the liver. In summary, defects in a liver-bone axis occur during HOD that can be targeted to ameliorate disease progression.
研究领域:
肝病学
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内分泌学
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代谢性疾病
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骨生物学
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DOI
PubMed
高影响因子
Cell Reports Medicine
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2024
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IF 11.7
Qianmin Gao,Yingying Jiang,Dongyang Zhou,Guangfeng Li,Yafei Han,Jingzhi Yang,Ke Xu,Yingying Jing,Long Bai,Zhen Geng,Hao Zhang,Guangyin Zhou,Mengru Zhu,Ning Ji,Ruina Han,Yuanwei Zhang,Zuhao Li,Chuandong Wang,Yan Hu,Hao Shen,Guangchao Wang,Zhongmin Shi,Qinglin Han,Xiao Chen,Jiacan Su
Patients with diabetes often experience fragile fractures despite normal or higher bone mineral density (BMD), a phenomenon termed the diabetic bone paradox (DBP). The pathogenesis and therapeutics opinions for diabetic bone disease (DBD) are not fully explored. In this study, we utilize two preclinical diabetic models, the leptin receptor-deficient db/db mice (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model. These models demonstrate higher BMD and lower mechanical strength, mirroring clinical observations in diabetic patients. Advanced glycation end products (AGEs) accumulate in diabetic bones, causing higher non-enzymatic crosslinking within collagen fibrils. This inhibits intrafibrillar mineralization and leads to disordered mineral deposition on collagen fibrils, ultimately reducing bone strength. Guanidines, inhibiting AGE formation, significantly improve the microstructure and biomechanical strength of diabetic bone and enhance bone fracture healing. Therefore, targeting AGEs may offer a strategy to regulate bone mineralization and microstructure, potentially preventing the onset of DBD.
研究领域:
医学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
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2017
·Vol. 40
·期 22
·4311-4319
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IF 2.557
Nani Wang,Qiaoyan Zhang,Hailiang Xin,Dan Shou,Luping Qin
A method using osteoblast membrane chromatography coupled with liquid chromatography and time-of-flight mass spectrometry was developed to recognize and identify the specific active components from traditional Chinese medicines. Primary rat osteoblasts were used for the preparation of the stationary phase in the cell chromatography method. Retention components from the cell chromatography were collected and analyzed by liquid chromatography with time-of-flight mass spectrometry. This method was applied in screening active components from extracts of four traditional Chinese medicines. In total, 24 potentially active components with different structures were retained by osteoblast cell chromatography. There were five phenolic glucosides and one triterpenoid saponin from Curculigo orchioides Gaertn, two organic acids and ten flavonoids from Epimedium sagittatum Maxim, one phthalide compound and one organic acid from Angelica sinensis Diels, and two flavonoids and two saponins from Anemarrhena asphodeloides Bunge. Among those, four components (icariin, curculigoside, ferulaic acid, and timosaponin BII) were used for in vitro pharmacodynamics validation. They significantly increased the osteoblast proliferation, alkaline phosphatase activity, levels of bone gla protein and collagen type 1, and promoted mineralized nodule formation. The developed method was an effective screening method for finding active components from complex medicines that act on bone diseases.
研究领域:
药理学
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分析化学
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中医药
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
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2019
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IF 2.895
Yiming Li,Guanhui Chen,Yi He,Xiliu Zhang,Binghui Zeng,Chao Wang,Chen Yi,Dongsheng Yu
Background Patients with metabolic bone diseases often have high risk of titanium implant failure due to compromised bone regeneration ability. Clinical evidence indicates that the poor osteogenic ability is partly because of excessive oxidative stress. To date, specific treatments for these patients are urgently needed. Ebselen, a non-toxic organoselenium compound, is reported to be a potent antioxidant agent. In this study, we hypothesized that ebselen exerted protective effects on osteogenic differentiation of bone-marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress. Methods BMSCs were isolated from SD rats, and their morphology and multiple differentiation abilities were characterized. Proliferation rates of BMSCs treated with different concentrations of ebselen were analyzed. Then BMSCs were pretreated by hydrogen peroxide (H 2 O 2 ), after which ebselen at different concentrations (0, 1, 5, 10 μM) was added, alkaline phosphatase (ALP) activity, mineralization and osteogenic-related protein levels were evaluated and an optimum concentration of ebselen was selected. Subsequently, intracellular reactive oxygen species (ROS) generation and the role of the PI3K/AKT pathway were also investigated. Results Ebselen within a proper range could promote the proliferation of BMSCs. H 2 O 2 -induced oxidative stress suppressed osteogenic differentiation of BMSCs, which was verified by the decrease in ALP activity, calcium deposition, Runx2 and β-catenin expression. However, ebselen could alleviate osteogenic dysfunction of BMSCs. We also observed that ebselen reduced ROS accumulation in H 2 O 2 -pretreated BMSCs. Moreover, the pro-osteogenic effects afforded by ebselen were almost abolished by the Akt inhibitor. Conclusion We concluded that ebselen could attenuate osteogenic dysfunction of BMSCs induced by H 2 O 2 through an antioxidant effect and the activation of the PI3K/Akt pathway, suggesting that ebselen has a potential therapeutic effect for patients with metabolic bone diseases.
研究领域:
干细胞生物学
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骨科
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2021
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IF 7.991
Wenqiang Li,Changpeng Xu,Lin Huang,Zhiguan Huang,Bin Zhou,Yuhe Li,Jianghui Dong,Liping Wang
Precise detection of Fe 3+ ions in vitro is important for diagnosis of disease and bone health. Covalent organic polymers (COPs) are chosen as the precision probes, due to their light-weight, stable-bonds, and fast-response. In this work, a new fluorescent COP, pyrene-2,7-diboronic-COP(PD-COP), was designed and its feasibility in detection of iron concentration in cells was tested. PD-COP showed good performance in selective detection of Fe 3+ , among other metal ions. Its high anti-interference property and recyclability provide the theoretical basis for practical applications. PD-COP could selectively detect Fe 3+ ions with low limit of detection (LOD) at a concentration of about 0.68 µM. The quenching mechanism could be due to the transfer of electron. The in vitro experiments using cells also showed that the PD-COP had good biocompatibility, and the ability to detect Fe 3+ ions in cells. In conclusion, we successfully synthesized a novel COP, with high sensitivity that could selectively detect Fe 3+ ions. The COP had the ability to enter the cell membrane and combine with iron ions, which provided a new method of monitoring bone health.
研究领域:
材料科学
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分析化学
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生物材料
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细胞生物学
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医学诊断
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产品关联
DOI
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-11
·
IF 16.6
Mi Chao,Zhang Xun,Yang Chengyu,Wu Jianqun,Chen Xinxin,Ma Chenguang,Wu Sitong,Yang Zhichao,Qiao Pengzhen,Liu Yang,Wu Weijie,Guo Zhiyong,Liao Jiayan,Zhou Jiajia,Guan Ming,Liang Chao,Liu Chao,Jin Dayong
Skeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Optical imaging through the near-infrared-II window (NIR-II, 1000–1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can passively target the bone marrow, which can be effective for over two months. We therefore develop the high-resolution NIR-II imaging method for bone disease diagnosis, including the 3D bone imaging instrumentation to show the intravital bone morphology. We demonstrate the monitoring of 1 mm bone defects with spatial resolution comparable to the X-ray imaging result. Moreover, NIR-II imaging can reveal the early onset inflammation as the synovitis in the early stage of rheumatoid arthritis, comparable to micro computed tomography (μCT) in diagnosis of osteoarthritis, including the symptoms of osteophyte and hyperostosis in the knee joint.
研究领域:
医学成像
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生物医学工程
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骨科
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纳米技术
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Tingting Chen,Zimei Wu,Qiaodan Hou,Yixin Mei,Kunkun Yang,Jing Xu,Lin Wang
Purpose Given the escalating prevalence of diabetes, the demand for specific bone graft materials is increasing, owing to the greater tendency towards bone defects and more difficult defect repair resulting from diabetic bone disease (DBD). Melatonin (MT), which is known for its potent antioxidant properties, has been shown to stimulate both osteogenesis and angiogenesis.Methods MT was formulated into MT@PLGA nanoparticles (NPs), mixed with sodium alginate (SA) hydrogel, and contained within a 3D printing polycaprolactone/β-Tricalcium phosphate (PCL/β-TCP) scaffold. The osteogenic capacity of the MT nanocomposite scaffold under diabetic conditions was demonstrated via in vitro and in vivo studies and the underlying mechanisms were investigated.Results Physicochemical characterization experiments confirmed the successful fabrication of the MT nanocomposite scaffold, which can achieve long-lasting sustained release of MT. The in vitro and in vivo studies demonstrated that the MT nanocomposite scaffold exhibited enhanced osteogenic capacity, which was elucidated by the dual angiogenesis effects activated through the NF-E2–related factor 2/Heme oxygenase 1 (Nrf2/HO-1) signaling pathway, including the enhancement of antioxidant enzyme activity to reduce the oxidative stress damage of vascular endothelial cells (VECs) and directly stimulating vascular endothelial growth factor (VEGF) production, which reversed the angiogenesis-osteogenesis uncoupling and promoted osteogenesis under diabetic conditions.Conclusion This study demonstrated the research prospective and clinical implications of the MT nanocomposite scaffold as a novel bone graft for treating bone defect and enhancing bone fusion in diabetic individuals.
研究领域:
生物材料
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组织工程
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再生医学
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糖尿病研究
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骨生物学
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药学
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纳米技术
✓ 已验证
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）