Materials Science & Engineering C-Materials for Biological Applications
·
2019
·
IF 4.959
Yimin Sun,Cheng Hu,Yuanyi Yang,Bin Dong,Yi Deng
The surface-inspirable biomaterials have captured extensive attention in simulating microenvironments by mimicking nanoscale architectures and signal molecules in the extracellular matrix (ECM). To activate osteogenic differentiation through biomimetic nanostructures, osteoid-like calcium titanate nanorods (CT) were fabricated via anodization and hydrothermal treatment. SEM, EDS, and XPS were employed to confirm the morphology and chemical composition. The functional fibroin and peptide layers on CT (PFCT) were subsequently applied to provide binding sites and bioactive molecules for osteoblast growth and differentiation. The hydrophilicity obviously increased with the protein layers. PFCT presented enhanced cell viability with pronounced pseudopod extension and continuous proliferation. The osteogenic differentiation analysis revealed that the alkaline phosphatase expression improved in the early stage. The calcium nodes and the collagen secretion were also enhanced. Quantitative polymerase chain reaction assessment indicated that osteogenesis-related markers including ALP , Col1 , and Runx2 , were up-regulated. The in vitro results demonstrated that fibroin/peptide co-functionalized calcium titanate nanorods were efficient to stimulate osteoblasts and improve cell adhesion, proliferation, and differentiation. Therefore, the nanorods can create an osteogenic niche on titanium implants, which can be a promising modification strategy in bone tissue engineering application.
研究领域:
材料科学
·
生物医学工程
·
组织工程
·
纳米技术
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2023
·Vol. 18
·期 1
·1-12
·
IF 2.6
Huang Jun,Zhou Hongxiang,He Liang,Zhong Lin,Zhou Ding,Yin Zongsheng
Background Nonunion is a failure of fracture healing and a major complication after fractures. Ubiquitin-specific protease 1 (USP1) is a deubiquitinase that involved in cell differentiation and cell response to DNA damage. Herein we investigated the expression, function and mechanism of USP1 in nonunion. Methods and results Clinical samples were used to detect the USP1 expression in nonunion. ML323 was selected to inhibit USP1 expression throughout the study. Rat models and mouse embryonic osteoblasts cells (MC3T3-E1) were used to investigate the effects of USP1 inhibition on fracture healing and osteogenesis in vivo and in vitro, respectively. Histological changes were examined by micro-computerized tomography (Micro-CT), hematoxylin & eosin (H&E) staining and Masson staining. Alkaline phosphatase (ALP) activity detection and alizarin red staining were used for osteogenic differentiation observation. The expression of related factors was detected by quantitative real-time PCR, western blot or immunohistochemistry (IHC). It was shown that USP1 was highly expressed in nonunion patients and nonunion rats. USP1 inhibition by ML323 promoted fracture healing in nonunion rats and facilitated the expression of osteogenesis-related factors and the signaling of PI3K/Akt pathway. In addition, USP1 inhibition accelerated osteogenic differentiation and promoting PI3K/Akt signaling in MC3T3-E1 cells. Conclusions USP1 inhibition plays a promotive role in coordinating osteogenic differentiation and fracture healing during nonunion. PI3K/Akt may be the downstream pathway of USP1.
研究领域:
骨科
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOTECHNOLOGY
·
2023
·
IF 2.6
Liu Hu,Li Tao,Ma Ben,Wang Yue,Sun Jun
Osteoblast regeneration, characterized by osteoblast differentiation, is the basis of fracture healing and accelerates fracture repair. It has been reported that hyaluronan and proteoglycan link protein 1 (HAPLN1) is overexpressed during osteoblast differentiation and regulates cartilage regeneration, but its function in fracture healing remains unclear. To elucidate this issue, we collected clinical blood samples of fracture healing, established a femoral fracture rat model, and induced an osteoblast differentiation cell model. We found that HAPLN1 was overexpressed in the serum of patients with fracture healing and the bone tissues of rats with fracture healing. Furthermore, the expression of HAPLN1 was increased time dependently during the osteogenic differentiation of MC3T3-E1 cells. HAPLN1 silencing prevented osteoblast differentiation and mineralization in MC3T3-E1 cells as evidenced by decreased osteoblast differentiation-related factors, suppressed alkaline phosphatase activities, and reduced alizarin red positive staining. Mechanically, the bone morphogenic protein 4 (BMP4)/Smad1/5/8 pathway, a facilitator of osteoblastic differentiation, was found to be inhibited by HAPLN1 knockdown, and inhibition of BMP4/Smad1/5/8 signaling enhanced the effects caused by HAPLN1 silencing. These findings demonstrated that HAPLN1 might promote fracture healing by facilitating osteogenic differentiation through the BMP4/Smad1/5/8 pathway, indicating that targeting HAPLN1 may be a feasible therapeutic candidate for fracture repair. Graphical Abstract
研究领域:
骨科
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2019
·Vol. 196
·期 1
·214-222
·
IF 2.431
Cao Zheng,Geng Xue,Jiang Xinpeng,Gao Xiang,Liu Kexiang,Li Yanfei
Aluminum (Al) inhibits osteoblast-mediated bone formation by oxidative stress, resulting in Al-induced bone disease. Melatonin (MT) has received extensive attention due to its antioxidant and maintenance of bone health effect. To evaluate the protective effect and mechanism of MT on AlCl 3 -induced osteoblast dysfunction, MC3T3-E1 cells were treated with MT (100 μM) and/or AlCl 3 (8 μM). First, MT alleviated AlCl 3 -induced osteoblast dysfunction, presenting as the reduced apoptosis rate as well as increased cell viability, alkaline phosphatase (ALP) activity, and type I collagen (COL-1) level. Then, MT significantly attenuated AlCl 3 -induced oxidative stress, presenting as the reduced reactive oxygen species and 8-hydroxy-2′-deoxyguanosine levels as well as increased glutathione level and superoxide dismutase activity. Finally, MT protected MC3T3-E1 cells against p53-dependent apoptosis and differentiation suppression, as assessed by Caspase-3 activity, protein levels of p53, Bcl-2-associated X protein (Bax), B cell lymphoma gene 2 (Bcl-2), cytosolic Cytochrome c, Runt-related transcription factor 2 (Runx2), and Osterix, as well as the mRNA levels of Bax, Bcl-2, Runx2, Osterix, ALP, and COL-1. Overall, our findings demonstrate MT attenuates AlCl 3 -induced apoptosis and osteoblastic differentiation suppression by inhibiting oxidative stress in MC3T3-E1 cells.
研究领域:
药理学
·
细胞生物学
·
毒理学
·
骨骼健康
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGICAL SCIENCES
·
2025
·
IF 2.9
Jingwei Liu,Cheng Qiu,Xiaoxiong Wang,Ziqian Xiang,Junyuan Sun,Mingzheng Chang,Qingliang Ma,Yan Zhuang,Yunpeng Zhao,Qiang Yang,Lianlei Wang,Xinyu Liu
Fracture is a common type of traumas and alternative therapies to boost bone fracture healing is necessary. The aim of this study is to elucidate the role of sulfasalazine in bone fracture healing by using MC3T3-E1 cells in vitro and murine femoral fracture model in vivo . Western blotting, flow cytometry, RNA sequencing, Calcein AM/PI staining, Alizarin-Red-S staining, ALP activity assay, transmission electron microscope, histological staining, immunohistochemistry, immunofluorescence and Surface plasmon resonance analysis were performed in this study. Sulfasalazine failed to elicit ferroptosis in osteoblasts within acceptable dose manner while promoted osteogenic differentiation. Furthermore, sulfasalazine was identified to inhibit inflammation by declination of inflammatory biomarkers. Besides, TNFα was verified as a potential downstream target for sulfasalazine and the adverse effect of TNFα on osteogenic differentiation could be largely salvaged by sulfasalazine due to direct binding between these two molecules. RNA-seq further implied decreased transcription of genes related to NF-κB pathway. Murine study showed sulfasalazine promotes fracture healing as evidenced by increased bone remodeling both histologically and radiologically. Overall, sulfasalazine accelerates osteogenic differentiation and promotes bone healing by direct binding to and thus inhibiting TNFα, which subsequently suppresses NF-κB signaling. Therefore, sulfasalazine shows a promising outcome for the treatment of bone fracture.
研究领域:
药理学
·
分子生物学
·
免疫学
·
骨科学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Yuqi Zhou,Guifang Wang,Tianqi Wang,Jiajia Wang,Xutao Wen,Haishui Sun,Lei Yu,Xiaoying Liu,Juanjuan Zhang,Qin Zhou,Yan Sun
Introduction The nanostructural modification of the oral implant surface can effectively mimic the morphology of natural bone tissue, allowing osteoblasts to achieve both proliferation and differentiation capabilities at the bone interface of the dental implant. To improve the osteoinductive activity on the surface of titanium implants for rapid osseointegration, we prepared a novel composite coating (MAO-PDA-NC) by micro-arc oxidation technique and immersion method and evaluated the proliferation, adhesion, and osteogenic differentiation of osteoblasts on this coating. Methods The coatings were prepared by micro-arc oxidation (MAO) technique and immersion method, and characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM) for different coatings; the loading of PDA was examined using Fourier transform infrared spectroscopy (FTIR); the ion release capacity of the coatings was determined by inductively coupled plasma emission spectrometry (ICP-OES); the interfacial bonding of the coatings was examined using nanoscratch experiment strength. The cytotoxicity of the coating was examined by live/dead staining kit; cell proliferation viability was examined by CCK-8 kit; adhesion and osteogenic effect of the coating were examined by immunofluorescence staining and RT-PCR; osteogenic differentiation was examined by alkaline phosphatase staining. Results The surface morphology of titanium implants was modified by micro-arc oxidation technology, and a new MAO-PDA-NC composite coating was successfully prepared. The results showed that the MAO-PDA-NC coating not only optimized the physical and chemical properties of the titanium implant surface but also significantly stimulated the biological properties of osteoblast adhesion, proliferation, and osteogenic differentiation on the coating surface. Conclusion These results show that MAO-PDA-NC composite coating can significantly improve the surface properties of titanium implants and achieve a stable bond between implant and bone tissue, thus accelerating early osseointegration.
研究领域:
生物材料
·
组织工程
·
口腔种植学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bio-Design and Manufacturing
·
2023
·
IF 7.9
Lu Jingyi,Sun Miao,Zhang Jingyu,Yang Xiaofu,Dong Minyi,He Huihui,Liu An,Yu Mengfei,Wang Baixiang,Wang Huiming
Regeneration and reconstruction of bone tissue is always a challenge for clinicians due to the uncertainty of bone repair materials in terms of long-term and efficient effects on osteoblasts. Here, we propose a novel strategy combining benidipine, an antihypertensive drug and nanoparticles to synergistically promote the healing of bone defects. Loose and porous benidipine-loaded magnesium silicate nanoparticles were prepared and validated for their biosafety. The nanoparticles were efficiently taken up by preosteoblasts and uniformly distributed around the nucleus. After internalization into cells, the nanosystem is degraded by lysosomes, and the effect of promoting osteogenic differentiation is reflected by the continuous release of benidipine, silicon and magnesium ions. Our results clearly evaluated that the nanoflower-like magnesium silicate delivering benidipine tends to be more appropriate for the bone regeneration in preosteoblasts, indicating that it might be a potential approach in guiding bone repair in clinical applications. Graphic abstract
研究领域:
生物医学工程
·
材料科学
·
组织工程
✓ 已验证
产品关联
DOI
高影响因子
MATERIALS LETTERS
·
2021
·
IF 3.423
Xiaoyu Wang,Mingyue Liu,Haiyan Li,Anlin Yin,Changlei Xia,Xiangxin Lou,Hongsheng Wang,Xiumei Mo,Jinglei Wu
A feasible approach to fabricate porous nanofibrous scaffolds structurally similar to native extracellular matrix was reported. Magnesium oxide (MgO) nanoparticles were incorporated into electrospun poly(lactic acid) (PLA)/gelatin membranes, which were processed into short fibers and reconstructed to three-dimensional scaffolds. The scaffold exhibited sponge-like appearance with interconnected pores ranging from 50 to 200 µm and was highly elastic. MgO nanoparticles hydrolyzed and alleviated the acidic degradation products of PLA/gelatin scaffold. Released magnesium ions were beneficial to pre-osteoblasts by promoting proliferation and by upregulating osteogenic differentiation, indicating that the scaffold might find opportunities for bone grafting materials.
研究领域:
生物材料学
·
组织工程学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Ma Fenbo,Li Sijing,L.I. Ruiz-Ortega,Zhang Yuanjun,Xu Lei,Wang Kui,Lin Lijun,Tang Bin
Repairing bone defects remains challenging in orthopedics. Here, strontium (Sr) alginate hydrogels containing chondroitin sulfate (CS) were fabricated for enhancing bone defects repair. The effects of CS incorporation ratio on the morphology, structure, thermal stability, water uptake and mechanical performance of Sr-CS/alginate hydrogels were also evaluated. Increasing CS incorporation ratio, Sr-CS/alginate hydrogels exhibit decreasing mechanical properties and lower water retention capacity. In vitro results suggest that Sr-CS/alginate hydrogels with higher CS ratio facilitate the proliferation of osteoblasts. Additionally, the osteogenic genes expressions were investigated by real-time quantitative polymerase chain reaction (RT-qPCR). The results reveal that Sr-CS/alginate hydrogels should have positive effects on modulating the osteogenic factors. Moreover, by employing repair femoral cylindrical defects rabbit model, the efficiency of as-fabricated Sr-CS/alginate hydrogels in bone regeneration was evaluated. The animal study suggests that Sr-CS/alginate hydrogel could significantly facilitate bone defects repair and therefore should potentially be useful for osteochondral tissue engineering.
研究领域:
骨科
·
组织工程
·
材料科学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2015
·
IF 2.084
Zheng Cao,Yang Fu,Xudong Sun,Qiuyue Zhang,Feibo Xu,Yanfei Li
Exposure to aluminum (Al) suppresses bone formation. Osteoblastic differentiation plays a key role in the process of bone formation. However, the effect of Al on osteoblastic differentiation is still controversial, and the mechanism remains unclear. To investigate the effect of Al on osteoblastic differentiation and whether Wnt signaling pathway was involved in it, the primary rat osteoblasts were exposed to 1/40 IC50, 1/20 IC50 and 1/10 IC50 of aluminum trichloride (AlCl 3 ) for 24 h, respectively. The activity analysis of alkaline phosphate, qRT-PCR analysis of type I collagen, alkaline phosphate, Wnt3a and Dkk-1, Western blot analysis of p-GSK3β, GSK3β and β-catenin protein and Immunofluorescence staining for β-catenin suggested that AlCl 3 inhibited osteoblastic differentiation and Wnt/β-catenin pathway. Moreover, we found exogenous Wnt3a application reversed the inhibitory effect of AlCl 3 on osteoblastic differentiation, accompanied by activating the Wnt/β-catenin pathway. Taken together, these findings suggest that AlCl 3 inhibites osteoblastic differentiation through inactivation of Wnt/β-catenin pathway in osteoblasts.
研究领域:
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Fangze Guo,Changqing Yuan,Hailin Huang,Xuyang Deng,Zirui Bian,Danyang Wang,Keke Dou,Li Mei,Qihui Zhou
Nano-hydroxyapatite (nHA) has been widely applied as a tissue-engineering biomaterial and interacted with osteoblasts/stem cells to repair bone defects. In addition, T cells that coexist with osteoblasts/stem cells in the bone modulate the regulation of osteoimmunology by cytokine formation. However, the effects of nHA on T cells and the following regulatory interplay on osteogenic differentiation have been rarely examined. In this work, the physicochemical properties of needle-like nHA are characterized by field emission scanning electron microscopy, zeta potential, Fourier transform-infrared and X-ray diffraction. It is found that as the concentration of nHA increases, the proliferation of T cells gradually increases, and the proportion of apoptotic T cells decreases. The percentage of CD4 + T cells is higher than that of CD8 + T cells under the regulation of needle-like nHA. Furthermore, the supernatant of T cells co-cultured with nHA significantly inhibits the osteogenic differentiation of MC3T3-E1 by downregulating the formation of alkaline phosphatase and calcium nodule compared with the supernatant of nHA. Thus, our findings provide new insight into the nHA-mediated T cell and osteoblast interactions.
研究领域:
生物材料
·
免疫学
·
组织工程
·
骨生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Yonglin Yu,Xinkun Shen,Zhong Luo,Yan Hu,Menghuan Li,Pingping Ma,Qichun Ran,Liangliang Dai,Ye He,Kaiyong Cai
Oxidative stress is commonly existed in bone degenerative disease (osteoarthritis, osteoporosis etc .) and some antioxidants had great potential to enhance osteogenesis. In this study, we aim to investigate the anti-oxidative properties of various TiO 2 nanotubes (TNTs) so to screen the desirable size for improved osteogenesis and reveal the underlying molecular mechanism in vitro . Comparing cellular behaviors under normal and oxidative stress conditions, an interesting conclusion was obtained. In normal microenvironment , small TNTs were beneficial for adhesion and proliferation of osteoblasts, but large TNTs greatly increased osteogenic differentiation . However, after H 2 O 2 (300 μM) treatment (mimicking oxidative stress), only large TNTs samples demonstrated superior cellular behaviors of increased osteoblasts' adhesion, survival and differentiation when comparing with those of native titanium (control). Molecular results revealed that oxidative stress resistance of large nanotubes was closely related to the high expression of integrin α5β1 (ITG α5β1), which further up-regulated the production of anti-apoptotic proteins (p-FAK, p-Akt, p-FoxO3a and Bcl2) and down-regulated the expression of pro-apoptotic protein (Bax). Moreover, we found that Wnt signals (Wnt3a, Wnt5a, Lrp5, Lrp6 and β-catenin) played an important role in promoting osteogenic differentiation of osteoblasts under oxidative condition.
研究领域:
材料科学
·
生物材料
·
细胞生物学
·
生物医学工程
✓ 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）