JOURNAL OF MATERIALS RESEARCH
·
2021
·Vol. 36
·期 9
·1866-1882
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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
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生物材料
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细胞生物学
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微生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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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
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组织工程
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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
CELL BIOLOGY INTERNATIONAL
·
2019
·Vol. 44
·期 2
·402-411
·
IF 2.127
Guiling Zhu,Bin Ma,Penghong Dong,Junjun Shang,Xiaochuan Gu,Ying Zi
Melatonin has been reported to participate in bone metabolism in recent studies. However, the underlying mechanism in melatonin-mediated osteoblastic differentiation remains largely unknown. The aim of this study is to investigate the role of melatonin in osteoblastic differentiation. In the present study, additional melatonin significantly promoted osteoblastic differentiation of MC3T3-E1 cells as evidenced by increased messenger RNA (mRNA) levels of osteogenic markers, alkaline phosphatase (ALP), collagen type I α1 chain, osteocalcin, and runt-related transcription factor 2 (Runx2). It was noteworthy that the expression level of platelet-derived growth factor subunit B (PDGFB) and content of its homodimer PDGF-BB were remarkably increased after melatonin administration. Moreover, the mRNA levels of phosphorylated PDGFRβ (PDGF receptor β) and Akt, a serine/threonine-specific protein kinase, were significantly upregulated in melatonin-treated MC3T3-E1 cells determined by a real-time polymerase chain reaction. Besides, by performing alizarin red staining, osteoblastic differentiation of MC3T3-E1 cells was conspicuously promoted by melatonin, which could be partially attenuated by crenolanib, a PDGFR inhibitor. Similarly, results from immunofluorescence and western blot assay showed that melatonin-induced upregulation of Runx2 and phosphorylated Akt was suppressed by crenolanib. Akt inhibition by MK-2206 also suppressed osteoblastic differentiation. Furthermore, by in vivo assay, additional melatonin promoted osteoblastic differentiation in mice with femoral fracture, and obvious callus formation was observed in melatonin-treated mice 5 weeks after fracture. Melatonin supplement also inhibited osteoclastic differentiation in mice. All statistical analysis was performed using GraphPad Prism and a P < 0.05 was deemed to be significant. To summarize, we demonstrate that melatonin promotes osteoblastic differentiation in MC3T3-E1 cells and enhances fracture healing in mouse femoral fracture model and regulates PDGF/AKT signaling pathway.
研究领域:
骨骼生物学
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药理学
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细胞信号传导
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·
IF 6.1
Feng Zhang,Jia Xu,Yanzhou Hu,Jingjing Fang,Minglan Yang,Kunlun Huang,Wentao Xu,Xiaoyun He
Aging is a major cause of bone loss and osteoporosis. Diallyl trisulfide (DATS), one of the main organic sulfides in garlic oil, has been shown to alleviate arthritis in mice. However, further research is still needed to determine how DATS affects bone formation and bone loss in aging mice. Here, we established a mouse model of natural aging for dietary DATS intervention. DATS treatment improved bone microstructure, including the disorganized arrangement of bone trabeculae and promoted collagen synthesis, with micro-CT and histological analyses. The abundance of beneficial bacteria for bone formation, such as Clostridiaceae and Erysipelotorichaceae, as well as the microbial diversity and community richness, were all altered by DATS, according to 16S rRNA sequencing data. 14 potential biomarkers and 9 important metabolic pathways were examined using serum metabolomics analysis. Additionally, there has been a significant reduction in sphingosine, which was directly associated with bone metabolism. The level of sphingosine and relative abundance of Clostridium were found to be negatively correlated by correlation analysis, indicating that bacteria may regulate bone reconstruction via influencing metabolites. Furthermore, Runx2 and β-catenin gene expression levels increased in bone, which may be related to the ameliorative mechanism of DATS. Our results suggested that DATS may prevent age-related bone loss by upregulating osteogenic gene expression through altering gut microbes and serum metabolism.
研究领域:
老年学
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药理学
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微生物学
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代谢组学
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骨生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HUMAN GENE THERAPY
·
2023
·
IF 4.2
Dr. Zhiguang Chen,Ms. Qi Zhao,Mr. Ran Zhang,Dr. Lianghong Chen,Mr. Songlan Gao,Dr. Yu Wang,Dr. Tiegang Li,Dr. Jinqi Xue
Substantial advances have been made in understanding the role of partial PDZ and LIM domain (PDLIM) family’s proteins in skeletal-related diseases. Yet, little is known about the effect of Pdlim1 on osteogenesis and fracture repair. This study aimed to investigate whether direct gene delivery using an adenovirus vector carrying Pdlim1 (Ad-oePdlim1) or encoding shRNA-Pdlim1 (Ad-shPdlim1) could affect the osteogenic activity of pre-osteoblastic MC3T3-E1 cells in vitro, and influence the fracture healing of mice in vivo. We found that Ad-shPdlim1 transfection contributed to the calcified nodule formation in MC3T3-E1 cells. Downregulation of Pdlim1 enhanced the alkaline phosphatase (ALP) activity and increased the expression of osteogenic markers (Runx2, Col1A1, osteocalcin and osteopontin). Further analysis indicated that Pdlim1 knockdown could activate β-catenin signaling, as evidenced by the accumulation of β-catenin in the nucleus and the increase levels of downstream regulators such as Lef1/Tcf7, Axin2, Cyclin D1 and Sox9. By contrast, Pdlim1 overexpression resulted in inhibition of the osteogenic activity of MC3T3-E1 cells. In vivo, at day 3 after fracture, Ad-shPdlim1 adenovirus particles were injected into the fracture site of the femur of mice, and the process of fracture healing was evaluated by X-ray, Micro-CT and histological examination. Local injection of Ad-shPdlim1 promoted the early cartilage callus formation, restored bone mineral density and accelerated cartilaginous ossification, with the upregulation of osteogenic gene (Runx2, Col1A1, osteocalcin and osteopontin) expression and activation of β-catenin signaling. Thus, we concluded that inhibition of Pdlim1 contributed to osteogenesis and fracture healing by activating the β-catenin signaling pathway.
研究领域:
分子生物学
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骨科
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再生医学
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基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Mingxin Qiao,Zhengyi Xu,Xibo Pei,Yanhua Liu,Jian Wang,Junyu Chen,Zhou Zhu,Qianbing Wan
Hyperlipidemia negatively affects osteogenesis, thereby impairing bone healing. However, few biomaterials have been developed for bone tissue engineering to solve this problem. Herein, the preparation of specific biomaterials that can promote osteogenesis and suppress adipogenesis holds great promise for reconstructive bone defect treatment. In this study, we propose the construction of a nano simvastatin-laden zeolitic imidazolate framework-8 (nano [email protected] ) modified injectable high-intensity biohydrogel, composed of poly (ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA) to form nano [email protected] /PEGDA/SA (defined as nSZPS), which can stimulate osteogenic differentiation and inhibit adipogenic differentiation. The characterization and drug loading efficiency of the nanoparticles were examined to confirm the successful synthesis of nano [email protected] Within the PEGDA/SA delivery platform, nSZPS showed excellent injectability and mechanical strength through rheological and mechanical tests. Moreover, owing to the sustained release of SIM and bioactive Zn ions, nSZPS not only possessed excellent biocompatibility but also significantly enhanced the osteogenic differentiation ability and inhibited the adipogenic efficacy of BMSCs in vitro. Furthermore, nSZPS showed excellent osseointegration and lipid-lowering abilities in healing bone defects of hyperlipidemic rats by decreasing PPARγ expression and increasing RUNX2 expression in vivo. In addition, the bidirectional regulatory mechanisms of nSZPS in bone defects may be closely related to the mutual regulation of the PPARγ and Wnt/β-CATENIN pathways. In summary, this nano [email protected] modified injectable high-intensity biohydrogel might be a promising strategy for complex bone regeneration, especially in hyperlipidemic microenvironments.
研究领域:
生物材料
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组织工程
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骨再生
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Runquan Zheng,Ning Zhang,Songbo Mao,Jiawei Li,Xuesong Yan,Guichun Zhang,Yongxian Zhang,Xianhu Yue
Bone defects and congenital bone deficiencies are common clinical conditions. However, conventional non-degradable artificial materials often lead to serious complications, such as severe infections and material displacement. The emergence of tissue engineering and the organoids concept presents a promising approach for the repair of bone defects, facilitating physiological reconstruction while minimizing complications. Nevertheless, previous studies have not developed injectable organoids that incorporates fully mineralized and organic microenvironments to achieve rapid osteogenesis and convenient application in bone regeneration. Therefore, it is imperative to devise an effective strategy to address these challenges. This study first prepared injectable GL scaffolds with varying concentrations and identified the optimal GL concentration for osteogenesis through systematic evaluation of osteogenic efficiency. Subsequently, inorganic salts of native bone (NBIS) and extracellular matrix from the periosteum (pECM) were integrated into the optimal GL scaffold to create an injectable scaffold featuring biomimetic mineralized and organic microenvironments. This scaffold was further utilized for in vitro analysis of osteogenic mechanisms and injected subcutaneously into rabbits for only four weeks to assess its osteogenic efficacy in vivo. The results indicated that the incorporation of NBIS and pECM significantly enhanced osteogenic efficacy by actively regulating ossification and ECM-receptor interaction signaling pathways, as well as upregulating RUNX2, ALP, COL1, and LAMA. This study introduces a promising injectable strategy for rapid osteogenesis using fully mineralized and organic biomimetic organoids.
研究领域:
组织工程
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骨再生
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生物材料
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医学生物技术
✓ 已验证
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2020
·Vol. 34
·期 3
·3583-3593
·
IF 4.966
Bu Yang,Shangfu Li,Zheng Chen,Feng Feng,Lei He,Bin Liu,Tianwei He,Xuan Wang,Ruiqiang Chen,Zihao Chen,Peigen Xie,Limin Rong
Background Amyloid β peptide (Aβ) is involved in osteoporosis, but the effects of Aβ on osteoblast and bone formation remain unclear. In this study, we investigated the effect of Aβ on bone formation. Methods An animal model of osteoporosis was established by ovariectomy in C57BL/6 mice. The mice received intraperitoneal injection of Aβ. The effect of Aβ on the osteogenic differentiation of human bone marrow stromal stem cells (hBMSCs) and differentiation of both pre-osteoblasts and pre-osteoclasts in a co-culture system were investigated. Results In the animal study, intraperitoneal injection of Aβ for 8 weeks promoted early and late osteogenic differentiation of hBMSCs. Aβ treatment significantly elevated osterix + (osteoblastic) cells but decreased TRAP + cells (osteoclasts) in the distal femur bone. In vitro study showed that Aβ treatment significantly enhanced matrix mineralization and osteogenic markers (Runx2 and osteocalcin). Aβ treatment activated Wnt/β-catenin signaling in hBMSCs. The effect of Aβ was blocked by DKK1 (a Wnt/β-catenin inhibitor) treatment. In the co-culture system, Aβ treatment significantly increased the ALP activities of MC3T3-E1 cells (pre-osteoblasts) but reduced the TRAP + RAW264.7 cells (pre-osteoclasts). Aβ treatment upregulated TCF1 and OPG proteins in MC3T3-E1 cells. Aβ treatment upregulated IκB-α but downregulated NFATc1protein in RAW264.7 cells. These effects were blocked by XAV-939 (a Wnt signaling antagonist), and then rescued by additional Wnt3a (a Wnt agonist). Conclusion Aβ treatment simultaneously promoted osteogenic differentiation via Wnt/β-catenin signaling, and inhibited osteoclasts differentiation via the OPG/RANKL/RANK system, suggesting Aβ is a positive regulator of osteoblast differentiation and bone formation.
研究领域:
生物学
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医学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2017
·Vol. 17
·期 1
·158-164
·
IF 1.692
Yang‑Hua Tang,Zhen‑Shuang Yue,Guo‑Song Li,Lin‑Ru Zeng,Da‑Wei Xin,Zhong‑Qing Hu,Can‑Da Xu
The aim of the present study was to investigate the effect of glucocorticoids in osteoblasts and to examine the role of β‑ecdysterone in the pathogenesis of glucocorticoid‑induced osteoporosis. Osteoblasts were induced from bone marrow mesenchymal stem cells, which were isolated from C57BL/6 mice. Cell viability and apoptosis of osteoblasts were measured by Cell Counting Kit‑8 and flow cytometry analysis, respectively. The expression of related genes and proteins was measured by reverse transcription quantitative polymerase chain reaction and western blot analysis respectively. Dose‑dependent decreases in the cell proliferation and differentiation were observed in dexamethasone (Dex)‑treated osteoblasts, evidenced by downregulation in the activity of alkaline phosphatasedecreased expression levels of Runt‑related transcription factor 2 and osteocalcin, and upregulated expression of RANK ligand. Dex also induced apoptosis and inhibited autophagy of osteoblasts, evidenced by upregulated B‑cell lymphoma 2 (Bcl‑2)‑associated X protein/Bcl‑2 ratio and the activation of mammalian target of rapamycin (mTOR), and decreased expression levels of Beclin‑1, autophagy protein 5 and microtubule‑associated protein 1 light chain 3 II. The effects on cell proliferation, apoptosis and autophagy induced by Dex were reversed by β‑ecdysterone in a dose‑dependent manner. Therefore, β‑ecdysterone may be a promising candidate drug for the treatment of osteoporosis through inducing osteoblast autophagic activity by inactivating mTOR.
研究领域:
药理学
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骨科
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Lu Tan,Yan Hu,Menghuan Li,Yuchen Zhang,Chencheng Xue,Maohua Chen,Zhong Luo,Kaiyong Cai
The biomineralization of calcium ions and phosphate ions in the extracellular matrix (ECM) is a key event in bone regeneration, and it’s of therapeutic significance to develop biomaterials capable of mimicking the physiological biomineralization process, which is especially desirable in cranial defect repairing. For this purpose, we design a composite remotely-activatable ECM-mimetic chitosan/collagen-based hydrogel incorporated with mesenchymal stem cell (MSC)-membrane-coated black phosphorus (BP), which is a photothermal material with versatile utility. Here, the MSC membrane-coated BP nanosheets could induce mild photothermal effect under near-infrared (NIR) light to stimulate the osteoblast recruitment via activating the heat shock proteins (HSPs)-mediated matrix metalloproteinase (MMP) and ERK-Wnt/β-catenin-RUNX2 axis. Meanwhile, the thermal decomposition of BP would release phosphate ions into the surrounding medium to attract calcium ions to form hydroxyapatite in the ECM in an in-situ manner, which is beneficial for osteoblast migration and osteogenic differentiation. After the implantation in to the cranial defect site on Sprague Dawley (SD) rats, it was evidently observed that the hydrogel treatment substantially enhanced the local bone density and promoted new bone formation. Overall, the ECM-mimetic BP-incorporated hydrogel could enhance osteoblast migration/differentiation and stimulate the biomineralization process under remote NIR activation to promote bone healing, which offers new opportunities for repairing cranial defect in the clinics.
研究领域:
生物材料
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组织工程
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骨再生
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光热疗法
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 23
·e70271
·
IF 4.3
Zongrui Yang,Yuanyuan Feng,Mingcai Zhang,Yongming Liu,Yizhe Xiong,Xiang Wang,Ying Shi,Bo Chen,Zhengming Wang,Haiya Ge,Hongsheng Zhan,Zhibi Shen,Guoqing Du
HBP-A is the main active component of a traditional Chinese medicine Huaizhen Yanggan Capsule, for the remarkable treatment of knee osteoarthritis (KOA). This study aimed to elucidate the ameliorative effect of HBP-A on meniscus hypertrophy and mineralisation in KOA and the molecular mechanism of its action. An Hartley guinea pig model of KOA that underwent anterior cruciate ligament transection (ACLT) and a model of rat primary meniscus fibrochondrocytes (PMFs) were used to investigate the ameliorative effect of HBP-A on meniscal hypertrophy and calcification and its signal transduction mechanism of action. The results show that Guinea pig's meniscus width, as well as the area of meniscus calcification and meniscus and articular cartilage injury score, were significantly reduced in the HBP-A intervention group compared to the ACLT group. The expression levels of mtrix metalloproteinase 13 (MMP13), runt-related transcription factor 2 (Runx2), Indian hedgehog (Ihh), alkaline phosphatase (ALP), and ankylosis homologue (ANKH) at the protein and gene level significantly decreased in the HBP-A intervention group compared to the ACLT group. In vitro study, apoptosis, hypertrophy, and calcification of rat PMFs after 10% stretch force were significantly improved with HBP-A intervention. Western blot and RT-qPCR showed that hypertrophy, calcification, and p38 MAPK signalling pathway-related markers of PMFs were incredibly depressed in the HBP-A intervention group compared to the 10% stretch force group. In conclusion, HBP-A can slow down meniscus hypertrophy and mineralisation induced by abnormal mechanical loading, and its mechanism of action may be through the p38-MAPK signalling pathway.
研究领域:
药理学
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骨科
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分子生物学
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传统中药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Zuoxiang Dong,Jian Xu,Peng Lun,Zeyu Wu,Wenshuai Deng,Peng Sun
Given the widespread clinical demand, addressing irregular cranial bone defects poses a significant challenge following surgical procedures and traumatic events. In situ-formed injectable hydrogels are attractive for irregular bone defects due to their ease of administration and the ability to incorporate ceramics, ions, and proteins into the hydrogel. In this study, a multifunctional hydrogel composed of oxidized sodium alginate (OSA)-grafted dopamine (DO), carboxymethyl chitosan (CMCS), calcium ions (Ca2+), nanohydroxyapatite (nHA), and magnesium oxide (MgO) (DOCMCHM) was prepared to address irregular cranial bone defects via dynamic Schiff base and chelation reactions. DOCMCHM hydrogel exhibits strong adhesion to wet tissues, self-healing properties, and antibacterial characteristics. Biological evaluations indicate that DOCMCHM hydrogel has good biocompatibility, in vivo degradability, and the ability to promote cell proliferation. Importantly, DOCMCHM hydrogel, containing MgO, promotes the expression of osteogenic protein markers COL-1, OCN, and RUNX2, and stimulates the formation of new blood vessels by upregulating CD31. This study could provide meaningful insights into ion therapy for the repair of cranial bone defects.
研究领域:
材料科学
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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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骨科
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）