EUROPEAN JOURNAL OF PHARMACOLOGY
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2019
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IF 3.17
Hailin Liu,Xiuli Zhang,Xinglong Zhong,Zehua Li,Shaoai Cai,Pingzhen Yang,Caiwen Ou,Minsheng Chen
The risk of cardiovascular events in patients with chronic kidney disease is tremendously increased due to vascular calcification . Local vascular inflammation significantly promotes vascular calcification. A previous study has shown that puerarin inhibits calcification of mouse vascular smooth muscle cells (VSMCs) in vitro, but whether puerarin can inhibit vascular calcification in vivo and the underlying mechanisms remain unclear. In this study, we found that rat VSMCs treated with calcifying medium showed more mineral deposition, and this effect was inhibited by puerarin in a dose-dependent manner, as detected by alizarin red staining and calcium content assay. Puerarin also prevented the trans-differentiation of VSMCs into osteoblast-like cells, indicated by down-regulation of bone-related genes including Runx2 and BMP2 . In vivo study of uremic rats induced by renal nephrectomy further confirmed the inhibitory effect of puerarin on vascular calcification in uremic rats. Puerarin treatment significantly prevented mineral deposition in rat aortas and down-regulated the expression of Runx2 and BMP2. Furthermore, we detected the levels of pro-inflammatory cytokines including IL-1β, IL-6, IL-18 and TNFα in vitro and in vivo . The levels of IL-1β were remarkably increased in both calcified VSMCs and aortas of uremic rats, while puerarin treatment markedly decreased the expression of IL-1β. In addition, we found that puerarin reduced IL-1β possibly through targeting NLRP3/Caspase1/IL-1β and NF-κB signaling pathways and inhibiting the generation of reactive oxygen species . Taken together, we demonstrated that puerarin has the capability of inhibiting vascular calcification in uremic rats by inhibiting inflammation.
研究领域:
药理学
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心血管疾病
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肾脏疾病
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炎症
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PubMed
高影响因子
ACS Applied Bio Materials
·
2026
·Vol. 9
·期 15
·6927-6940
·
IF 5.6
Peng Haorui,Zhang Yulin,Dai Qiyuan,Ding Yilin,Chen Hexuan,Zhang Shuai,Luo Huitong,Cao Xiaodong
The management of bone injuries arising from traumatic or pathological origins necessitates biomaterial platforms that bridge immediate hemorrhage control and long-term osteogenic guidance within a single implantable system. In this study, we fabricated a chitosan-based composite cryogel (CMS-BG/BMP2) using dual-template mesoporous bioactive glass (dMBG). By using the double-template agent method, we enhanced the specific surface area of bioactive glass, optimized its pore architecture, improved the loading efficiency of bone morphogenetic protein 2 (BMP2), and achieved its controlled release, thereby circumventing the adverse effects caused by excessive local concentration of BMP2. The cryogel exhibited over 20 kPa compressive strength, favorable cyclic compression resistance, and controlled degradation (∼50% mass loss in 28 days). Hemocompatibility assays confirmed its safety, while dMBG incorporation enhanced blood cell adhesion and hemostatic efficacy without compromising biocompatibility. In vitro tests showed that the composite promoted mice bone marrow mesenchymal stem cells (BMSCs) migration and osteogenic differentiation by upregulating ALP activity, calcium nodule formation, and osteogenesis-related genes. This multifunctional material integrates hemostasis, structural support, and bioactivity, offering great potential for the clinical treatment of hemorrhagic bone defects.
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高影响因子
Biomaterials Advances
·
2022
·
IF 0
Weida Zhuang,Genlan Ye,Jiachang Wu,Leyu Wang,Guofang Fang,Zhuofeng Ye,Guohua Lai,Xiaozhong Qiu,Hongxun Sang
Integration of biological factors and hierarchical rigid scaffolds is of great interest in bone tissue engineering for fabrication of biomimetic constructs with high physical and biological performance for enhanced bone repair. Core/shell microspheres (CSMs) delivering bone morphogenetic protein-2 (BMP-2) and a strategy to integrate CSMs with 3D-printed scaffolds were developed herein to form a hybrid 3D system for bone repair. The scaffold was printed with polycaprolactone (PCL) and then coated with polydopamine. Shells of CSMs were electrosprayed with alginate. Cores were heparin-coated polylactic acid (PLA) microparticles fabricated via simple emulsion and heparin coating strategy. Assembly of microspheres and scaffolds was realized via a self-locking method with the assistance of controlled expansion of CSMs. The hybrid system was evaluated in the rat critical-sized bone defect model. CSMs released BMP-2 in a tunable manner and boosted osteogenic performance in vitro . CSMs were then successfully integrated inside the scaffolds. The assembled system effectively promoted osteogenesis in vitro and in vivo . These observations show the importance of how BMP-2 is delivered, and the core/shell microspheres represent effective BMP-2 carriers that could be integrated into scaffolds, together forming a hybrid system as a promising candidate for enhanced bone regeneration.
研究领域:
组织工程
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生物医学工程
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材料科学
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再生医学
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DOI
PubMed
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2022
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IF 3.712
Fan Zhang,Jingxing Li,Chengxiong Gu,Haibo Zhang
Background The role and function of microRNA (miRNA, miR)-140-5p in the calcification of vascular smooth muscle cells (VSMCs) have been explored in this study.Methods The calcium nodules formed in transfected and β-glycerophosphate (β-GP)-treated VSMCs were observed using Alizarin Red S staining, and alkaline phosphatase (ALP) activity was determined. VSMC apoptosis was detected with flow cytometry assay. The target gene of miR-140-5p was predicted and confirmed with dual-luciferase reporter assay. Relative expressions of miR-140-5p, toll like receptor 4 (TLR4) and vascular calcification-related proteins (α-smooth muscle actin, α-SMA; Msh Homeobox 2, MSX2; bone morphogenetic protein 2, BMP2; Kruppel-like factor 4, KLF4; Runt-related transcription factor 2, RUNX2) were measured through quantitative real time polymerase chain reaction (qRT-PCR) and western blot.Results MiR-140-5p upregulation reversed the effects of β-GP on downregulating miR-140-5p and α-SMA expressions, enhancing ALP activity, calcium nodule formation and cell apoptosis, and upregulating levels of MSX2, BMP2, KLF4 and RUNX2. TLR4 was the target of miR-140-5p, and offset the effects of miR-140-5p on β-GP-induced VSMCs.Conclusions MiR-140-5p upregulation represses β-GP-induced calcification of VSMCs via targeting TLR4, providing a potential therapeutic method for vascular calcification.
研究领域:
分子生物学
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心血管疾病
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细胞生物学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Dong Huang,Xin Hou,Dawei Zhang,Qian Zhang,Chunyan Yan
Cibotium barometz , an important traditional Chinese medicine, is used in strengthening bones and tendons. We found that C. barometz crude polysaccharides (CB70) could alleviate bone loss and markedly improve the biomechanical properties of OVX rats. Thus, to clarify biological active ingredient(s) of CB70, two homogeneous polysaccharides (CBP70-1-1 and CBP70-1-2) were purified from CB70. A combination of monosaccharide composition, FT-IR, GC–MS and NMR analysis indicated that CBP70-1-1 was composed of →6)-D-Gal p -(1→, D-Glc p -(1→, →3,6)-D-Man p -(1→, →4)-D-Glc p -(1→ and →6)-D-Glc p -(1→ with relative molecular weights of 12,724 Da, and CBP70-1-2 was composed of →4)-D-Glc p -(1→, D-Glc p -(1→, →3,6)-D-Man p -(1→, →6)-D-Gal p -(1→, →4,6)-D-Glc p -(1→ and →3)-L-Ara f -(1→ with relative molecular weights of 3611 Da. Morphological analyses revealed that CBP70-1-1 and CBP70-1-2 appeared as a sheet that were irregular in size and shape, while the surface of CBP70-1-1 was full of sharp protuberances and CBP70-1-2 was smooth. Furthermore, the effects of CBP70-1-1 and CBP70-1-2 on the proliferation, differentiation and mineralization of mouse pre-osteoblastic MC3T3-E1 cells were assessed via CCK-8 assay, alkaline phosphatase activity assay, and alizarin red-based assay, respectively. These results revealed that CBP70-1-1 and CBP70-1-2 significantly promoted the proliferation, differentiation and mineralization of MC3T3-E1 cells, even better than E2. More importantly, quantitative real-time PCR and Western blot analysis indicated that CBP70-1-2 pronouncedly promoted the expression of osteogenic-related marker genes ( Runx2, Osx, Ocn and Opn ) and proteins (BMP2, RUNX2, OSX and p-SMAD1), which implies that the osteogenic activity of CBP70-1-2 is accomplished mainly by activating the BMP2/SMAD1 signaling pathway. These findings suggest CBP70-1-2 as a potential natural anti-osteoporotic agent for pharmacotherapy.
研究领域:
药理学
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分子生物学
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中医药学
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DOI
PubMed
高影响因子
Cell Stem Cell
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2025
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IF 20.4
Lei Fan,Qi Tang,Yutong Wang,Hang Sun,Ge Li,Yi Yang,Huiying Zhu,Zhaoyuan Liu,He Wang,Hongyan Wang,Qing Jing,Christopher L. Antos,Hui Xiao,Renchu Guan,Gang Pei,Florent Ginhoux,Zhigang Zhou,An Zeng
Adult hearts scar after injury, while neonatal hearts regenerate. The mechanisms underlying this dichotomy remain unclear. Through comparative spatiotemporal single-cell analyses and dual recombinase-mediated lineage tracing, we uncovered an injury-induced Clusterin + cardiomyocyte ( Clu + CM) population that coordinates reparative, anti-inflammatory macrophage activity. Following injury, Clu + CMs emerge in the border zone of regenerative hearts but are scarce in non-regenerative contexts. These CMs secrete CLU, which binds to macrophage Toll-like receptor 4 (TLR4), attenuating inflammation and promoting reparative polarization through Cpt1a -dependent fatty acid oxidation. These macrophages secrete bone morphogenetic protein 2 (BMP2), activating bone morphogenetic protein receptor, type 1A (BMPR1A) signaling in CMs to drive proliferation. Reduced CLU levels in myocardial infarction patients correlate with impaired cardiac function, whereas Clu overexpression or transplantation of engineered CLU + human cardiac organoids recapitulates this regenerative modulation, enhancing myocardial repair in adult mice. Our findings reveal a critical cardio-immune mechanism whereby Clu + CMs reprogram macrophages to resolve inflammation and stimulate CM proliferation, providing potential strategies for cardiac regeneration.
研究领域:
心脏病学
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免疫学
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再生医学
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分子生物学
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细胞信号传导
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Siyu Wu,Jiayi Ma,Jun Liu,Chun Liu,Su Ni,Ting Dai,Yan Wang,Yiping Weng,Hongbin Zhao,Dong Zhou,Xiubo Zhao
Biomaterial–immune system interactions play an important role in postimplantation osseointegration to retain the functionality of healthy and intact bones. Therefore, appropriate osteoimmunomodulation of implants has been considered and validated as an efficient strategy to alleviate inflammation and enhance new bone formation. Here, we fabricated a nanostructured PCL/PVP (polycaprolactone/polyvinylpyrrolidone) electrospinning scaffold for cell adhesion, tissue ingrowth, and bone defect padding. In addition, telmisartan, an angiotensin 2 receptor blocker with distinct immune bioactivity, was doped into PCL-/PVP-electrospun scaffolds at different proportions [1% (TPP-1), 5% (TPP-5), and 10% (TPP-10)] to investigate its immunomodulatory effects and osteoinductivity/conductivity. Telmisartan-loaded scaffolds displayed in vitro anti-inflammatory bioactivity on lipopolysaccharide-induced M1 macrophages by polarizing them to an M2-like phenotype and exhibited pro-osteogenic properties on bone marrow-derived mesenchymal stem cells (BMSCs). Histological analysis and micro-CT results of a rat skull defect model also showed that the telmisartan-loaded scaffolds induced a higher M2/M1 ratio, less inflammatory infiltration, and better bone regenerative patterns. Furthermore, activation of the BMP2 (bone morphogenetic protein-2)-Smad signaling pathway was found to be dominant in telmisartan-loaded scaffold-mediated macrophage–BMSC interactions. These findings indicate that telmisartan incorporation with PCL/PVP nanofibrous scaffolds is a potential therapeutic strategy for promoting bone healing by modulating M1 macrophages to a more M2 phenotype at early stages of postimplantation.
研究领域:
生物材料
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免疫学
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组织工程
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再生医学
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药理学
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产品关联
DOI
PubMed
高影响因子
CERAMICS INTERNATIONAL
·
2023
·
IF 5.2
Bo Li,Haocheng Yang,Hongli Song,Jie Zou,Chenchen Li,Ziyi Yan,Moyuan Qu,Wenqian Xiao,Songsong Zhu,Xiaoling Liao
Repairing bone defects is particularly challenging when an infection is presented. In this study, poly(L-lactic) (PLLA) nanofibrous microspheres (large microspheres) were used as cell carriers to simulate the nanofibrous structure of the extracellular matrix. A planet-satellite composite microsphere with large microspheres and small microspheres was constructed by bonding hollow Ag@SiO 2 nanospheres (small microspheres) to nanofibrous PLLA microspheres. According to the results, PLLA nanofibrous microspheres activated by EDC and NHS can firmly combine with Ag@SiO 2 nanospheres. The composite microspheres demonstrated excellent drug release functions, antibacterial properties, and biocompatibility and promoted cell adhesion and differentiation in vitro. The bone repair function of composite microspheres loaded with BMP2 growth factor was evaluated in rat that were infected with bacteria and exhibited skull defects. A four-week study showed that these microspheres significantly promoted bone regeneration in infected bone. These multifunctional microspheres could revolutionize bone repair and provide a much-needed solution for those suffering from infected bone defects.
研究领域:
材料科学
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生物医学工程
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组织工程
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骨科
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药剂学
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高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
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2022
·Vol. 59
·期 1
·1-9
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IF 2.723
Chen Sunyu,Xiao Zhanhao,Jiang Wenjin
Osteogenic differentiation is a crucial process of new bone formation. This study aimed to explore the roles and mechanism of SRY-Box Transcription Factor 2 (SOX2) on proliferation and osteogenic differentiation of MC3T3-E1 cells. Bone morphogenetic protein 2 (BMP2) was used to induce the osteogenic differentiation of MC3T3-E1 cells. The expression of SOX2 was determined by quantitative real-time PCR (RT-PCR) at different time points after induction. The SOX2 overexpression plasmids were constructed and transfected into MC3T3-E1 cells. Osteogenic differentiation was evaluated by Alizarin Red S staining and alkaline phosphatase (ALP) assay. The expressions of osteogenic differentiation markers including runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osteocalcin (OCN) were detected by western blot assay. Luciferase reporter and CHIP assays were used to confirm that SOX2 regulated the transcriptional activation of leucine-rich repeat-containing G protein–coupled receptor 4 (LGR4). We found that SOX2 was down-regulated upon BMP2-induced osteogenic differentiation in MC3T3-E1 cells. Overexpression of SOX2 effectively inhibited osteogenic differentiation with decreased ALP activity, calcification, and osteogenic differentiation markers’ expression including Runx2, OPN, and OCN. LGR4 was identified as a target of SOX2, and the inhibitory effect of SOX2 on osteogenic differentiation was reversed by knockdown of LGR4. The present study confirmed that SOX2 suppressed osteogenic differentiation of MC3T3-E1 cells through targeting LGR4, which possesses a therapeutic strategy for bone formation and generation.
研究领域:
分子生物学
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细胞生物学
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骨骼生物学
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转录调控
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Minghai Dai,Xiufei Lin,Peng Hua,Simeng Wang,Xiaoliang Sun,Chengxuan Tang,Chi Zhang,Liangle Liu
Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu 2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu 2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.
CAS / MDL:
研究领域:
生物医学工程
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组织工程
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材料科学
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骨科
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Yu Sun,Xiuhua Zhang,Wanrong Hong,Yingfeng Qin,Yunan Man,Maolin He,Jin-Wen Liu,Jia Chen
Growth factor holds great promise for bone regeneration, and spatiotemporal control of their expressing through site-specific reactions is crucial but challenging for on-demand therapy. In this study, we present the development of a novel unnatural amino acids (UAAs)-triggered therapeutic switch (UATS) system, composed of an orthogonal aminoacyl-tRNA-synthase (aaRS)-tRNA pair and a bone morphogenetic protein 2 (BMP2) gene harboring premature stop codon, which enable in situ and on-demand initiation of the expression of BMP2. The resulting UATS system allowed specifically control of base expressing on the BMP2 mRNA that switched to the BMP2 protein with complete structure and function to facilitate bone regeneration. Our investigations showed that the UATS system exhibits remarkable attributes of rapid, sensitive, reversible, and sustained BMP2 expression both in vitro and in vivo settings. Moreover, the implantation of microencapsulated cells with UATS system is applied to a mouse femur defect model, demonstrating high effciency in controlled expressing of BMP2 protein and substantial repair of bone defect following oral administration of UAAs. Therefore, our findings underscore the great potential of UATS system for on-demand awakening of functional growth factor, thus offering promising prospects in the realm of regenerative medicine.
研究领域:
再生医学
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分子生物学
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生物医学工程
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组织工程
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 44
·7052-7064
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IF 5.047
Hui Chi,Anlong Jiang,Xiaoyan Wang,Guanghua Chen,Chengchao Song,Ravi Kumar Prajapati,Ang Li,Zecheng Li,Jiaxin Li,Zhengye Zhang,Ye Ji,Jinglong Yan
Micro–nano based fibrous scaffolds have been extensively studied in regenerative medicine. Bone marrow stem cells (BMSCs) and BMP2-derived peptides, two other important components for tissue engineering, have been successfully used for bone regeneration. However, a scaffold that specifically captures BMSCs and delivers BMP2-derived peptides to promote osteogenic differentiation of enriched BMSCs has not been reported. In this study, a microfiber scaffold was constructed by coaxial electrospinning technology using a polyvinylpyrrolidone/bovine serum albumin/BMP2-derived peptide compound as the core solution and a polycaprolactone/collagen I compound as the shell solution. The scaffolds were further functionalized by covalent grafting of a BMSC affinity peptide (E7) to develop a dual drug release system for the delivery of the BMP2-derived peptide and E7. Structural analysis indicated that the microfibers had a uniform diameter and homogeneous core–shell structure. Fourier transform infrared spectroscopy (FTIR) revealed that E7 was covalently bonded onto the surface of the fibers. In vitro, the E7-modified scaffolds promoted the initial adhesion of BMSCs and were more favorable for BMSC survival. Furthermore, the BMP2-derived peptide loaded in the E7-modified scaffolds was released in a sustained manner and retained bioactivity, significantly improving the osteogenic differentiation of BMSCs. In vivo, scaffolds loaded with the BMP2-derived peptide and E7 (PCME scaffolds) led to enhanced new bone formation and defect closure in a rat calvarial defect model. Overall, the PCME scaffold simultaneously facilitated all three of the essential elements needed for bone tissue engineering, providing a promising method for bone regeneration.
研究领域:
再生医学
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组织工程
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生物材料科学
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干细胞生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）