Frontiers in Pharmacology
·
2024
·
IF 4.4
Xiaoqin Zhang,Jiale Mao,Lu Shao,Shuang Liu,Jiwang Zhou,Mingrong Mei,Zunjing Zhang
Background: Melastoma dodecandrum Lour. (MD), a traditional botanical drug known for its hypoglycemic, antioxidant, and anti-inflammatory properties, is commonly used to treat diabetes, osteoarthritis, and osteoporosis. However, its specific active components against diabetic osteoporosis remain unclear.Purpose: This study aimed to identify the key active components in MD using cell membrane chromatography coupled with mass spectrometry and validate their effects in vitro.Methods: An AGEs-induced osteoblast injury model was established. MTT assays measured cell viability, and ALP activity was assessed using a biochemical kit. Western blotting was employed to detect the expression levels of osteoblast-related proteins OCN and RUNX2 and the AGE receptor protein RAGE. ELISA was used to determine the levels of SOD, MDA, CAT, and GPx. PCR quantified TNF-α expression to evaluate the protective effects and potential mechanisms of MD. The AGEs-induced osteoblast cell membrane chromatography-mass spectrometry method facilitated the rapid identification of potentially active compounds based on their affinity for the osteoblast cell membrane. Cell experiments further validated the activity of the characteristic component isovitexin.Results: MD significantly improved cell viability in AGEs-damaged osteoblasts, enhanced ALP, SOD, CAT, and GPx activities, reduced MDA levels, increased OCN and RUNX2 protein expression, and decreased TNF-α mRNA and RAGE protein expression. Cell membrane chromatography identified 20 chemical constituents, including 13 flavonoids, 4 organic acids, 1 phenylpropanoids, 1 terpenoids, and 1 alkaloid. Cell experiments have confirmed that isovitexin has significant protective activity against osteoblasts and can inhibit the expression of specific receptor RAGE on the osteoblast membrane, consistent with the effect of MD.Conclusion: MD and its active component, isovitexin, provide protective effects against AGEs-induced osteoblast injury, offering a basis for subsequent drug development.
研究领域:
药理学
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生物化学
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细胞生物学
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分析化学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2019
·Vol. 9
·期 1
·1-10
·
IF 4.011
Wang Yaozong,Sun Naikun,Zhang Yinlong,Zhao Bin,Zhang Zheyi,Zhou Xu,Zhou Yuanyuan,Liu Hongyi,Zhang Ying,Liu Jianguo
This study explored the applicability, cellular efficacy, and osteogenic activities of porous nano-hydroxyapatite/Poly (glycerol sebacate)-grafted maleic anhydride (n-HA/PGS-g-M) composite scaffolds. Nuclear magnetic resonance (NMR) analyses indicated that approximately 43% of the hydroxide radicals in PGS were displaced by maleic anhydride. Resonance bands at 1036 cm −1 occurred in scaffolds containing nHA powders, and peak areas increased when n-HA weight increased in PGS-M-n-HA-0.4, PGS-M-n-HA-0.5, and PGS-M-n-HA-0.6 scaffolds. The n-HA/PGS-g-M composite scaffolds exhibited porous microstructure with average pore size of 150–300 µm in scanning electron microscopy (SEM) analysis. Differential scanning calorimetry (DSC) identified the glass transition temperature (Tg) as −25–30 °C, indicative of quality resilience. The modulus of compressibility increased when n-HA content increased. Interestingly, viability of human adipose-derived stem cells (hADSCs) in vitro and expression of the osteogenic related genes RUNX2 , OCN , and COL1A1 was enhanced in the n-HA/PGS-g-M composite scaffolds compared to those factors observed in PGS-g-M scaffolds. Finally, simulated body fluid (SBF) tests indicated more apatite deposits on the surface of n-HA/PGS-g-M scaffolds compared to PGS-g-M scaffolds. Overall, porous n-HA/PGS-g-M composite scaffolds possessed acceptable biocompatibility and mechanical properties, and they stimulated hADSC cell proliferation and differentiation. Given these qualities, the composite scaffolds have potential applications in bone tissue engineering.
研究领域:
组织工程
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生物材料科学
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干细胞研究
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材料科学
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产品关联
DOI
PubMed
高影响因子
Journal of Orofacial Orthopedics-Fortschritte der Kieferorthopadie
·
2024
·
IF 1.3
Pang Huiqi,Ding Luhua,Che Xiaoxia
Purpose We aimed to investigate early effects of regulating alpha‑7 nicotinic acetylcholine receptor (α7nAChR) agonists and antagonists on maxillary expansion in mice. Methods We allocated 36 six-week-old male C57BL/6J mice into three group: 1) expansion alone, 2) expansion plus the α7nAChR-specific agonist 3‑(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride (GTS-21), and 3) expansion plus alpha-bungarotoxin (α-BTX), a competitive antagonist of α7nAChR. The groups were daily injected with saline, GTS-21 (4 mg/kg/day) or α‑BTX (1 mg/kg/day), respectively, from days 0–7. In addition, a mouse model of maxillary expansion was established. Masson’s trichrome staining was used to observe morphological changes and immunohistochemistry was performed to analyze α7nAChR, interleukin (IL)-1β, IL‑6, tumor necrosis factor (TNF)-α, runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN) expression in the midpalatal suture. Microcomputed tomography was used to measure midpalatal suture and palatal basal bone widths. We assessed the normal distribution of our data using the Kolmogorov–Smirnoff test and evaluated the homogeneity of variance by Levene’s test, followed by a two-way ANOVA and Bonferroni tests at a significance level of P < 0.05. Results In the GTS-21+expansion group, osteogenesis was more active in the middle palatine suture. New bone was calcified and deposited in the suture and we observed decreased IL-1β, IL‑6, and TNF‑α expression ( P < 0.05). In the α‑BTX+expansion group, we observed increased proinflammatory cytokine and decreased RUNX2 and OCN expression and increased midpalatal suture and palatal basal bone widths ( P < 0.05). Conclusion Using α7nAChR agonists and antagonists to regulate the cholinergic anti-inflammatory pathway, the secretion of inflammatory factors and osteoblast markers during maxillary expansion were altered, indicating the potential for clinical modulation of maxillary palatal suture expansion.
研究领域:
牙科学
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免疫学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2024
·
IF 2.3
Chao Han,Dingsong Lu,Suoping Yang,Chong Liu,Feng Guo,Kai Zhang,Peng Li
The design and construction of a new and excellent synthetic graft is of great significance in the field of bone defect repair and reconstruction. In this study, a dopamine modified chitosan hydrogel doped with Cu ions with a mild photothermal effect was designed to provide a better microenvironment to advance the bone repair via promote the angiogenesis and osteogenesis. Characterizations showed the successful synthesis of the material while it also presented excellent biocompatibility and mild photothermal effect under the irradiation of near-infrared light. Further, it could enhance the angiogenesis of HUVECs cells through promoting the ability of migration and tube formation and enhance the osteogenic differentiation of MC3T3-E1 cells via increasing the content of vital osteogenic factors including Runx2, Col-1, OPN, OCN, OSX, etc. The in vivo experiment also testified that it could promote the bone defect repair in rat models. These results indicate the multifunctional hydrogel is an ideal material for the treatment of bone defects and has good clinical application potential.
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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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Junkai Zeng,Changjiang Gu,Feihui Zeng,Youzhuan Xie
Implant-associated infection (IAI) is an unsolved problem in orthopaedics. Current therapies, including antibiotics and surgical debridement, can lead severe clinical and financial burdens on patients. Therefore, there is an urgent need to reinforce the inherent antibacterial properties of implants. Recently, two-dimensional (2D) silicene nanosheets (SNs) have gained increasing attention in biomedical fields owing to their considerable biocompatibility, biodegradability and strong photothermal-conversion performance. Herein, a dual-functional photosensitive coating on a Ti substrate (denoted as TPSNs) was rationally fabricated for bacterial inhibition and osteogenesis promotion. For the first time, SNs were loaded onto the surface of implants. Hyperthermia generated by the SNs and polydopamine (PDA) coating under 808 nm laser irradiation achieved the in vitro anti-bacterial efficiency of 90.7 ± 2.4 % for S. aureus and 88.0 ± 5.8 % for E. coli , respectively. In addition, TPSNs exhibited promising biocompatibility for the promotion of BMSC (bone marrow mesenchymal stem cells) proliferation and spreading. The presence of silicon (Si) in TPSNs contributed to the improved osteogenic differentiation of BMSCs, elevating the expressions of RUNX2 and OCN. In animal experiments, the combination of TPSNs with photothermal therapy (PTT) achieved an anti-bacterial efficiency of 89.2 % ± 1.6 % against S. aureus . Furthermore, TPSNs significantly improved bone-implant osseointegration in vivo . Overall, the development of a dual-functional TPSNs coating provides a new strategy for combating IAI.
研究领域:
生物材料
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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
COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
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IF 4.389
Bolin Tang,Xiaojun Shen,Yaru Yang,Zhi Xu,Jie Yi,Yongbo Yao,Miao Cao,Yalin Zhang,Hongqin Xia
Cellular responses can be regulated and manipulated through combining stimuli-responsive biomaterial with external stimulus. In this present, the magneto-responsive CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings were designed to understand cell behaviors of preosteoblasts, as well as get insight into the underlying mechanism of osteogenic differentiation under static magnetic field (SMF). CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings with differential magnetic property (low, medium and high magnetization) were prepared by incorporation of different mass fraction of CoFe 2 O 4 nanoparticles (6%, 13 %, 20 %) into P(VDF-TrFE) matrix. Cell experiments indicated that all nanocomposite coatings with the assistance of SMF could promote the cell attachment, proliferation and osteogenic differentiation of MC3T3-E1 cells. Among different nanocomposite coatings, low magnetization coating (6%) showed a higher ALP activity and gene expression of Runx2, Col-I, OCN. Molecular biology assays demonstrated that the combination of nanocomposite coatings and SMF could significantly up-regulate the expression level of α2β1 integrin and p-ERK. Whereas, the addition of inhibitor U0126 down-regulated sharply the expression level of p-ERK, which indicated that cellular osteogenic differentiation of MC3T3-E1 cells was governed through α2β1 integrin-mediated MEK/ERK signaling pathways during CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings were combined with SMF. This work provided a promising strategy to enhance cellular osteogenic differentiation through a remote-control manner, which exhibited great potential in the application of bone tissue repair and regeneration.
研究领域:
生物材料
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组织工程
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细胞生物学
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磁性材料
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再生医学
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DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR BIOLOGY
·
2024
·Vol. 70
·期 3
·95-101
·
IF 1.5
Shanfu Wang,Bing Xu,Heng Yin,Zhen Hua,Yang Shao,Jianwei Wang
Osteoporosis is a common chronic bone disorder in postmenopausal women. Ginsenosides are primary active components in ginseng and the effects of various ginsenoside variants in osteoporosis treatment have been widely revealed. We planned to explore the impact of ginsenoside Rc on bone resorption in an osteoporosis rat model. We used ovariectomized rats to assess the potential impact of ginsenoside Rc on osteoporosis. μ-CT was implemented for analyzing the microstructure of the distal left femur in rats. H&E staining together with Masson staining were applied for bone histomorphometry evaluation. ELISA kits were implemented to detect serum concentrations of TRACP-5b, OCN, CTX, as well as PINP. Ginsenoside Rc treatment lessened the serum levels of TRACP-5b as well as CTX, while increasing serum levels of OCN, and PINP of OVX rats. Moreover, we found that ginsenoside Rc contributed to the synthesis of type I collagen via increasing Col1a1 and Col1a2 levels in femur tissues of ovariectomized rats. Our findings also revealed that ginsenoside Rc activated the TGF-β/Smad pathway by increasing TGF-β as well as phosphorylated Smad2/3 protein levels. Ginsenoside Rc alleviates osteoporosis in rats through promoting the TGF-β/Smad pathway.
研究领域:
药理学
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骨科
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内分泌学
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分子生物学
✓ 已验证
DOI
高影响因子
Acta Biomaterialia
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2018
·
IF 6.383
Ye He,Caiyun Mu,Xinkun Shen,Zhang Yuan,Ju Liu,Weizhen Chen,Chuanchuan Lin,Bailong Tao,Bin Liu,Kaiyong Cai
Titanium (Ti) and Ti-alloys were widely used in clinic orthopedics, however, the insufficient bone formation surrounding Ti-based implants still limited their biological performances. Surface modification of Ti substrates is essential to improve their interactions with bone-forming cells and bone tissue. In this study, we modified Ti substrates by coating peptide LL-37 onto micro-structured Ti substrates and aimed to (i) induce mesenchymal stem cells (MSCs) migration both in vitro and in vivo , (ii) facilitate osteogenic differentiation of MSCs and new bone formation. The surface micro-structured Ti substrates with hydroxyapatite deposition were fabricated by a two-step method including micro-arc oxidation (MAO) and hydrothermal treatment. LL-37 was loaded on micro-structured Ti substrates with the assistance of polydopamine coating. We confirmed that surface-modified Ti substrates benefited viability, adhesion, migration and osteogenic differentiation of MSCs in vitro . In a femur-defect rat model, the surface-modified Ti implants effectively induced CD29 + /CD90 + positive cells migration in one week after implantation. According to the results of H&E, Masson’s trichrome staining and immunohistochemical staining of OCN , OPN and collagen I, the targeted Ti implants exhibited significant new bone formation after implantation for 4 weeks. These results indicate that the surface modification of Ti samples facilitated bone formation through MSCs recruitment. Statement of Significance The inherent surface bioinertness of titanium (Ti) and Ti-alloys still limits their biological performances in clinical applications. Recently, the strategy of mesenchymal stem cells (MSCs) recruitment has been proposed to improve the osteointegration of bone implants. Herein, we reports the surface modification of Ti implants from the point of MSCs recruitment. Peptide LL-37 was coated on micro-structured Ti substrates to (i) recruit MSCs, (ii) regulate bio-physiological performance of MSCs, and (iii) facilitate bone formation in vivo. Our results improve the understanding of the interaction between Ti implants and MSCs, and provide a promising strategy of MSCs recruitment in the design of bone repair related biomaterials.
研究领域:
生物材料
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组织工程
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骨科
·
干细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Zuyun Yan,Tianshi Sun,Wei Tan,Zhicheng Wang,Jinpeng Yan,Jinglei Miao,Xin Wu,Pei Feng,Youwen Deng
In the system of magnesium-loaded scaffolds, the effect of magnesium ions (Mg 2+ ) on the osteogenesis induction is restricted due to the low transmembrane transport efficiency of Mg 2+ into the cell, which limits the application for bone defect repair. Inspired by the fact that magnetic field can regulate ion channel proteins on the cell membrane, magnetite nanoparticle is introduced into the poly (l-lactic acid) /magnesium oxide composite in this study, and a magnetic magnesium-loaded bone scaffold is prepared via selective laser sintering . Notably, the activities of the Mg 2+ channel protein (MAGT1) on the membrane of bone marrow mesenchymal stem cells (rBMSCs) are enhanced via magnetic torque effect (via integrin α V β 3/actin), under the action of static magnetic field (SMF), which promoted rBMSCs to capture Mg 2+ in the microenvironment and induced osteogenesis. In vitro experiments showed that the magnetic magnesium-loaded scaffold, under the action of SMF, can accelerate the inflow of Mg 2+ from surrounding microenvironment, which improved cellular activities, osteogenesis-related gene expression (ALP, Runx2, OCN, and OPN), and mineralization. Besides, in vivo skull defect repair experiments showed that the scaffolds possessed good ability to promote bone differentiation and new bone regeneration.
研究领域:
生物材料
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组织工程
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生物医学工程
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细胞生物学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Jianfeng OuYang,Bingquan Li,Kangsheng Yang,Wenyi Gan,Xiaogang Miao,Bo Bai,Caiqin Lin,Jiewei Peng,Xiaofei Zheng
Modern developments in bone tissue engineering focus on designing biomimetic materials that exhibit suitable mechanical and physiochemical properties. In this study, we present the development of a new biomaterial scaffold using a newly constructed polymer that contains bisphosphonate in combination with gelatin (GAT). To achieve scaffolding, a chemical grafting technique was used to develop risedronate (RS)-functionalized polycaprolactone (PCL-RS). The freeze-casting process was used to construct the porous PCL-RS/GAT scaffold after incorporating gelatin into the PCL-RS polymer solution. A scaffold with pores that are in perfect position and a porosity of 81.84% was successfully acquired. The biodegradability assessment, 48% of its early weight was lost after five weeks. The PCL-RS/GAT scaffold exhibited an elastic modulus of 32.01 MPa and a tensile strength of 3.9 MPa. The MTT analysis showed the PCL-RS/GAT favorable cytocompatibility with rat bone marrow-derived mesenchymal stem cells (BM-MSC). In addition, the cells cultured in the PCL-RS/GAT scaffold exhibited the greatest ALP activity and mineralization. The RT-PCR test results indicated that the PCL-RS/GAT scaffold had a high RUNX2, COL 1A1, and OCN gene expression, suggesting a strong osteoinductive capacity. The results indicate that the PCL-RS/GAT scaffold is a suitable biomimetic platform for tissue engineering in bone.
研究领域:
生物材料
·
组织工程
·
生物医学工程
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干细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Bioengineered
·
2021
·
IF 3.269
Xiaochen Wang,Yaochuan Mi,Wei He,Xiaona Hu,Shuo Yang,Lu Zhao,Yanyang Zhang,Binhong Wen
Diabetic osteoporosis (DOP) is a chronic complication of diabetes in the skeletal system. High level of miR-340-5p may be harmful to the bone formation. In this study, the DOP model of rats was successfully established via streptozotocin (STZ) and ovariectomy (OVX) treatment. It was manifested by reduced body weight, insulin level, alkaline phosphatase (ALP) activity, and osteocalcin (OCN) and collagen-I expressions, as well as increased concentration of fasting blood glucose. Moreover, we found that miR-340-5p expression was increased while runt-related transcription factor-2 (RUNX2) was decreased in femurs. Furthermore, the effects of miR-340-5p on osteogenic differentiation (OD) in high glucose (HG)-treated MC3T3-E1 cells were explored. Exposure to OD and HG contributed to elevated miR-340-5p level. Inhibition of miR-340-5p enhanced ALP level, calcium deposition, and OCN, collagen-I and RUNX2 levels. On the contrary, miR-340-5p overexpression reversed these promotional effects. Luciferase assay indicated that RUNX2 may be a target gene of miR-340-5p. Moreover, RUNX2 deficiency decreased miR-340-5p inhibition-induced ALP activity, calcium accumulation and OCN, collagen-I, RUNX2 levels. In short, the above findings revealed that inhibition of miR-340-5p facilitated osteogenic differentiation through regulating RUNX2 in MC3TC-E1 cells, which provided targeted therapeutic strategies for the treatment of DOP.
研究领域:
分子生物学
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内分泌学
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骨生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS RESEARCH
·
2021
·Vol. 36
·期 9
·1866-1882
·
IF 3.089
Wu Jin,Liu Yajing,Zhang Hao,Wu Yizhen,Chu Zhuangzhuang,Wu Qirong,Lu Mengmeng,Tang Chunbo
Abstract In this study, we presented that human bone mesenchymal stem cells (hBMSCs) showed superior adhesion and proliferation behaviors on polished silicon nitride (Si 3 N 4 ). Also, compared to Ti and ZrO 2 , Si 3 N 4 enhanced the osteogenic activities of hBMSCs indicated by increases in alizarin red S (ARS) staining, Ca 2+ concentration, and mRNA expression of RUNX2, OPN, OCN, and COL1. Furthermore, colony formation assays demonstrated significantly better antibacterial activities against oral pathogens Porphyromonas gingivalis (Pg), Staphylococcus aureus (SA), and Escherichia coli ( E. coli ) on Si 3 N 4 surface than Ti and ZrO 2 . Live/dead bacterial staining showed a large amount of dead Pg on Si 3 N 4 surfaces. The fact that Si 3 N 4 demonstrated advantages in osteogenic and antibacterial activities over Ti and ZrO 2 might be a reason for its potential use as non-metallic dental implant materials. However, more detailed studies with resolution techniques and preclinical studies are needed to confirm the Si 3 N 4 ’s osteogenic and antibacterial properties. Trial registration number PJ2019-066-001; date of registration: Jun 2019. Graphic abstract
研究领域:
牙科学
·
生物材料
·
细胞生物学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）