BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2024
·
IF 4.2
Bin Wang,Wei Wang,Jingyu Li,Jianjun Li
The molecular mechanism underlying the promotion of fracture healing by mechanical stimuli remains unclear. The present study aimed to investigate the role of zinc finger protein 36 like 2 (ZFP36L2)-histone deacetylase 1 (HDAC1) axis on the osteogenic responses to moderate mechanical stimulation. Appropriate stimulation of fluid shear stress (FSS) was performed on MC3T3-E1 cells transduced with ZFP36L2 and HDAC1 recombinant adenoviruses, aiming to validate the influence of mechanical stress on the expression of ZFP36L2-HDAC1 and the osteogenic differentiation and mineralization. The results showed that moderate FSS stimulation significantly upregulated the expression of ZFP36L2 in MC3T3-E1 cells ( p < 0.01). The overexpression of ZFP36L1 markedly enhanced the levels of osteogenic differentiation markers, including bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), Osterix, and collagen type I alpha 1 (COL1A1) ( p < 0.01). ZFP36L2 accelerated the degradation of HDAC1 by specifically binding to its 3’ UTR region, thereby fulfilling its function at the post-transcriptional regulatory gene level and promoting the osteogenic differentiation and mineralization fate of cells. Mechanical unloading notably diminished/elevated the expression of ZFP36L2/HDAC1, decreased bone mineral density and bone volume fraction, hindered the release of osteogenic-related factors and vascular endothelial growth factor in callus tissue ( p < 0.01), and was detrimental to fracture healing. Collectively, proper stress stimulation plays a crucial role in facilitating osteogenesis through the promotion of ZFP36L2 and subsequent degradation of HDAC1. Targeting ZFP36L2-HDAC1 axis may provide promising insights to enhance bone defect healing.
研究领域:
骨科
·
分子生物学
·
细胞生物学
·
生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Zhang Peng,Wang Tiehua,Qian Junyu,Qin Haotian,Liu Peng,Xiong Ao,Udduttula Anjaneyulu,Wang Deli,Zeng Hui,Chen Yingqi
Microbial infections of bones, particularly after joint replacement surgery, are a common occurrence in clinical settings and often lead to osteomyelitis (OM). Unfortunately, current treatment approaches for OM are not satisfactory. To address this issue, this study focuses on the development and evaluation of an injectable magnesium oxide (MgO) nanoparticle-coordinated phosphocreatine-grafted chitosan hydrogel (CMPMg-VCM) loaded with varying amounts of vancomycin (VCM) for the treatment of OM. The results demonstrate that the loading of VCM does not affect the formation of the injectable hydrogel, and the MgO-incorporated hydrogel exhibits anti-swelling properties. The release of VCM from the hydrogel effectively kills staphylococcus aureus bacteria, with CMPMg-VCM (50) showing the highest antibacterial activity even after prolonged immersion in PBS solution for 12 days. Importantly, all the hydrogels are non-toxic to MC3T3-E1 cells and promote osteogenic differentiation through the early secretion of alkaline phosphatase and calcium nodule formation. Furthermore, in vivo experiments using a rat OM model reveal that the CMPMg-VCM hydrogel effectively kills and inhibits bacterial growth, while also protecting the infected bone from osteolysis. These beneficial properties are attributed to the burst release of VCM, which disrupts bacterial biofilm, as well as the release of Mg ions and hydroxyl by the degradation of MgO nanoparticles, which inhibits bacterial growth and prevents osteolysis. Overall, the CMPMg-VCM hydrogel exhibits promising potential for the treatment of microbial bone infections.
研究领域:
生物医学工程
·
药剂学
·
骨科手术
·
材料科学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2018
·
IF 1.911
Li-Jun Deng,Yan-Lin Wu,Xian-Hua He,Ke-Nan Xie,Lu Xie,Yi Deng
A strategy developed for obtaining positive cellular responses remains to be focused in the filed of functional biomimetics. In this study, a hydrogel covered simvastatin-loaded polyetheretherketone (PEEK) bio-composites was constructed with the purpose of bone tissue regeneration therapy. Briefly, a three-dimensional (3D) porous structure was fabricated on PEEK surface; then the substrate was functionalized with the poly(L-lactic acid)/simvastatin porous film and hyaluronic acid hydrogel subsequently. In vitro cell attachment, proliferation, and cytoskeletal observation experiments reveal that our scaffolds show better bio-affinity due to the layer of hyaluronic acid hydrogel compared with control. Furthermore, the alkaline phosphatase activity, calcium mineral deposition evaluation, and gene expression for osteogenic potential all exhibit that the superior osteogenic differentiation of MC3T3-E1 pre-osteoblasts on our scaffolds. Therefore, our PEEK samples loaded with simvastatin and covered with hyaluronic acid hydrogel hold great potential in clinical applications for bone repair.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 6
·
IF 6.353
Jiang Yingying,Tan Shuo,Hu Jianping,Chen Xin,Chen Feng,Yao Qianting,Zhou Zhi,Wang Xiansong,Zhou Zifei,Fan Yunshan,Liu Junjian,Lin Yize,Liu Lijia,He Shisheng
The seek of bioactive materials for promoting bone regeneration is a challenging and long-term task. Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials. Herein, amorphous calcium magnesium phosphate (ACMP) nanoparticles and simvastatin (SIM)-loaded ACMP (ACMP/SIM) nanocomposites were developed via a simple co-precipitation strategy. The physiochemical property of ACMP/SIM was explored using transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and high-performance liquid chromatograph (HPLC), and the role of Mg2+ in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure (XANES). After that, the transformation process of ACMP/SIM in simulated body fluid (SBF) was also tracked to simulate and explore the in vivo mineralization performance of materials. We find that ACMP/SIM releases ions of Ca2+, Mg2+ and PO3−4, when it is immersed in SBF at 37°C, and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite (HAP). Furthermore, ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells. For the in vivo studies, lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria. ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12 weeks. The bioactive ACMP/SIM nanocomposites are promising as bone repair materials. Considering the facile preparation process and superior in vitro/vivo bioactivity, the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.
研究领域:
生物材料
·
生物医学工程
·
骨组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Guofeng Wang,Yaxin Zhu,Xingjie Zan,Meng Li
There is a substantial global market for orthopedic implants, but these implants still face the problem of a high failure rate in the short and long term after implantation due to the complex physiological conditions in the body. The use of multifunctional coatings on orthopedic implants has been proposed as an effective way to overcome a range of difficulties. Here, a multifunctional (TA@HA/Lys) n coating composed of tannic acid (TA), hydroxyapatite (HA), and lysozyme (Lys) was fabricated in a layer-by-layer (LBL) manner, where TA deposited onto HA firmly stuck Lys and HA together. The deposition of TA onto HA, the growth of (TA@HA/Lys) n , and multiple related biofunctionalities were thoroughly investigated. Our data demonstrated that such a hybrid coating displayed antibacterial and antioxidant effects, and also facilitated the rapid attachment of cells [both mouse embryo osteoblast precursor cells (MC3T3-E1) and dental pulp stem cells (DPSCs)] in the early stage and their proliferation over a long period. This accelerated osteogenesis in vitro and promoted bone formation in vivo . We believe that our findings and the developed strategy here could pave the way for multifunctional coatings not only on orthopedic implants, but also for additional applications in catalysts, sensors, tissue engineering, etc.
研究领域:
生物材料
·
骨科
·
组织工程
·
生物医学工程
·
纳米技术
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2023
·Vol. 15
·期 20
·9148-9161
·
IF 6.7
Zheng Liu,Hong Ding,Miaomiao He,Yulin Jiang,Lin Qi,Meixuan Du,Jing Wang,Yubao Li,Limin Liu,Ganjun Feng,Li Zhang
Desirable antibacterial and osseointegration abilities are essentially important for long-term survival of a Ti-orthopedic implant. Herein, a near-infrared light (NIR) excited antibacterial platform with excellent osseointegration composed of perovskite calcium titanate/nickel hydroxide on a Ti implant (Ni(OH)2@CaTiO3/Ti) was designed and successfully fabricated. The construction of the heterostructure efficiently separated the photogenerated electron–hole pairs to produce sufficient reactive oxygen species (ROS), which enabled the photoactivated bacterial inactivation (PBI) of Ti implants. The results showed that the surface-modified Ti implant displayed remarkable antibacterial ability with bacterial inhibition rates of 95.5% for E. coli and 93.8% for S. aureus under NIR excitation. Also, the intervention of Ni(OH)2 could create a slightly alkaline surface on the Ti implant, which synchronized with Ca-rich CaTiO3 to regulate the osteogenic microenvironment in favor of the adhesion, proliferation and differentiation of MC3T3-E1 cells as well as the up-regulation of osteogenesis-related gene expressions. The in vivo implantation experiments further confirmed that the heterostructured coating prominently accelerated the formation of new bone and promoted the osseointegration of Ti implants. Our work may provide a novel concept for improving the antibacterial and osseointegration abilities of Ti implants in orthopedic and dental applications.
研究领域:
材料科学
·
生物材料
·
骨科
·
牙科科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Zhongyuan Zhang,Wenshu Xu,Zhenhua Zhang,Xiaoxue Chen,Hui Jin,Ningning Jiang,Hui Xu
This study was to investigate the potential mechanisms of treatment with metformin (Met) combined with kaempferol (Kae) against postmenopausal osteoporosis. Experiments were conducted in both ovariectomy (OVX)-induced osteoporosis rats and in vitro using RAW264.7 cells, MC3T3-E1 cells, and HUVECs. Results demonstrated the therapeutic effect of Met combined with Kae on osteoporosis. In vivo, Kae alone and in combination with Met treatments enhanced tibial trabecular microstructure, bone mineral density (BMD), and mechanical properties in OVX rats without causing hepatotoxicity and nephrotoxicity. It also reduced bone resorption markers (CTX-1 and TRAP) and increased the bone formation marker (PINP) level in the serum of OVX rats. The expression of bone resorption marker TRAP was reduced, while bone formation markers Runx2 and ALP were enhanced in the bone tissue of OVX rats. Furthermore, Met combined with Kae also promoted the expression of angiogenesis-related markers CD31 and VEGF in OVX rats. In vitro, MC3T3-E1s cells treated with Met combined with Kae showed higher expression of ALP, Runx2, and VEGF. Interestingly, the treatment did not directly promote HUVECs migration and angiogenesis, but enhanced osteoblast-mediated angiogenesis by upregulating VEGF levels. Additionally, Met combined with Kae treatment promoted VEGF secretion in MC3T3-E1, and activated the Notch intracelluar pathway by upregulating HES1 and HEY1 in HUVECs. Meantime, their stimulation on CD31 expression were inhibited by DAPT, a Notch signaling inhibitor. Overall, this study demonstrates the positive effects of Met combined with Kae on osteoporotic rats by promoting osteogenesis-angiogenesis coupling, suggesting their potential application in postmenopausal osteoporosis.
研究领域:
药理学
·
骨科
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2024
·
IF 4.5
Zhiguang Chen,Qi Zhao,Lianghong Chen,Songlan Gao,Lingshuai Meng,Yingjie Liu,Yu Wang,Tiegang Li,Jinqi Xue
Osteogenic differentiation is important for fracture healing. Microfibrial-associated glycoprotein 2 (MAGP2) is found to function as a proangiogenic regulator in bone formation; however, its role in osteogenic differentiation during bone repair is not clear. Here, a mouse model of critical-sized femur fracture was constructed, and the adenovirus expressing MAGP2 was delivered into the fracture site. Mice with MAGP2 overexpression exhibited increased bone mineral density and bone volume fraction (BV/TV) at Day 14 postfracture. Within 7 days postfracture, overexpression of MAGP2 increased collagen I and II expression at the fracture callus, with increasing chondrogenesis. MAGP2 inhibited collagen II level but elevated collagen I by 14 days following fracture, accompanied by increased endochondral bone formation. In mouse osteoblast precursor MC3T3-E1 cells, MAGP2 treatment elevated the expression of osteoblastic factors (osterix, BGLAP and collagen I) and enhanced ALP activity and mineralization through activating β-catenin signaling after osteogenic induction. Besides, MAGP2 could interact with lipoprotein receptor-related protein 5 (LRP5) and upregulated its expression. Promotion of osteogenic differentiation and β-catenin activation mediated by MAGP2 was partially reversed by LRP5 knockdown. Interestingly, β-catenin/transcription factor 4 (TCF4) increased MAGP2 expression probably by binding to MAGP2 promoter. These findings suggest that MAGP2 may interact with β-catenin/TCF4 to enhance β-catenin/TCF4's function and activate LRP5-activated β-catenin signaling pathway, thus promoting osteogenic differentiation for fracture repair. mRNA sequencing identified the potential targets of MAGP2, providing novel insights into MAGP2 function and the directions for future research.
研究领域:
骨骼生物学
·
骨科
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Sustainable Chemistry & Engineering
·
2020
·
IF 7.632
Wenyan Li,Xiangheng He,Kun Liu,Wei Wen,Lu Lu,Mingxian Liu,Changren Zhou,Binghong Luo
The commonly used chitin whiskers (CHWs) prepared by the acid hydrolysis method are easy to agglomerate in an alkaline matrix, which limits their applications in many aspects. Herein, maleation chitin whiskers (mCHWs) with lots of −COOH groups were designed, which can stably exist and homogeneously disperse in the alkaline chitin matrix due to their relatively strong electronegativities. Subsequently, the CHWs and mCHWs were utilized as reinforcing fillers to enhance the mechanical strength of the chitin hydrogel. As expected, the CHWs played an extremely limited role in reinforcing the chitin hydrogel. Conversely, due to good dispersibility and strong interfacial interaction, the mCHWs exhibited a significantly superior enhancement effect on the chitin hydrogel. Moreover, the tensile strength and modulus of the as-prepared mCHW/chitin composite hydrogels were strongly dependent on the content of mCHWs, and the highest values of 5.8 ± 0.2 and 5.2 ± 0.6 MPa were obtained with 3 wt % mCHW content, which are higher than those of polysaccharide hydrogels reported in the most literature. Importantly, both CHWs and mCHWs can facilitate the adhesion, proliferation, and differentiation of mouse embryo osteoblast precursor (MC3T3-E1) cells. Moreover, the mCHWs also play these promoting effects in a content-dependent manner. Interestingly, CHWs and mCHWs mainly contain −NH2 and −COOH groups, respectively; as a result, surface protein adsorption and calcium-phosphate mineralization are different. But there are very small differences in cell adhesion, proliferation, and differentiation between the corresponding 3%CHW/chitin and 3%mCHW/chitin composite hydrogels. This work provides a promising strategy to construct a polysaccharide nanocomposite hydrogel with robust mechanical strength and osteogenesis for potential application as an artificial periosteum.
研究领域:
材料科学
·
生物医学工程
·
生物材料
·
组织工程
✓ 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
·
药理学
·
细胞信号传导
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Yingqi Chen,Weibei Sheng,Jianjing Lin,Chongzhou Fang,Jiapeng Deng,Peng Zhang,Meng Zhou,Peng Liu,Jian Weng,Fei Yu,Deli Wang,Bin Kang,Hui Zeng
Natural polysaccharide (NPH)-based injectable hydrogels have shown great potential for critical-sized bone defect repair. However, their osteogenic, angiogenic, and mechanical properties are insufficient. Here, MgO nanoparticles (NPs) were incorporated into a newly synthesized water-soluble phosphocreatine-functionalized chitosan (CSMP) water solution to form an injectable hydrogel (CSMP-MgO) via supramolecular combination between phosphate groups in CSMP and magnesium in MgO NPs to circumvent these drawbacks of chitosan-based injectable hydrogels. Water-soluble chitosan deviate CSMP was first synthesized by grafting methacrylic anhydride and phosphocreatine into a chitosan chain in a one-step lyophilization process. The phosphocreatine in this hydrogel not only provides sites to combine with MgO NPs to form supramolecular binding but also serves as the reservoir to control Mg2+ release. As a result, the lyophilized CSMP-MgO hydrogels presented a porous structure with some small holes in the pore wall, and the pore diameters ranged from 50 to 100 μm. The CSMP-MgO injectable hydrogels were restricted from swelling in DI water (lowest swelling ratio was 16.0 ± 1.1 g/g) and presented no brittle failure during compression even at a strain above 85% (maximum compressive strength was 195.0 kPa) versus the control groups (28.0 and 41.3 kPa for CSMP and CSMP-MgO (0.5) hydrogels), with regulated Mg2+ release in a stable and sustained manner. The CSMP-MgO injectable hydrogels promoted in vitro calcium phosphate (hydroxyapatite (HA) and tetracalcium phosphate (TTCP)) deposition in supersaturated calcium phosphate solution and presented no cytotoxicity to MC3T3-E1 cells; the CSMP-MgO hydrogel promoted MC3T3-E1 cell osteogenic differentiation with upregulation of BSP, OPN, and Osterix osteogenic gene expression and mineralization and HUVEC tube formation. Among them, CSMP-MgO (5) presented most of these properties. Moreover, this hydrogel (CSMP-MgO (5)) showed an excellent ability to promote new bone formation in critical-sized calvarial defects in rats. Thus, the CSMP-MgO injectable hydrogel shows great promise for bone regeneration.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2021
·Vol. 110
·期 2
·273-286
·
IF 4.396
Kai Li,Hongchuan Tian,Ai Guo,Liguo Jin,Weizhen Chen,Bailong Tao
Bacterial infection and poor osteogenic capacity can result in the loosing or failure of titanium (Ti)-based implants in the clinic. Therefore, it is urgent to design an effective approach to enhance the osteogenic property and restrict bacterial activity. In this study, a layered double hydroxide (LDH) composed of Ga and Sr ions on Ti substrates by a hydrothermal method, then calcined in 250°C and denoted as LDH250. The scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were confirmed that the LDH films were successfully formed on the Ti substrates. Importantly, the obtained LDH films can induce an alkaline microenvironment around the Ti surface and regulate the behaviors of osteogenic cells and bacteria. In vitro cellular experiments, the LDH250 can enhance the differentiation of both MC3T3-E1 cells and osteoblasts, stimulate alkaline phosphatase activity (ALP), collagen secretion, and mineralization levels. Meanwhile, antimicrobial assay against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) demonstrated that the LDH250 samples had strong antibacterial abilities, which attributed to the release profile of Ga 3+ could act as a “Trojan horse” to destroy the bacterial iron metabolism, inducing of local alkaline environment, and producing reactive oxygen species. Hence, this study provides an effective method for reducing antibacterial infection and enhancing the bone integrative capacity of Ti-based implants for orthopedic applications.
研究领域:
材料科学
·
生物医学工程
·
骨科
·
生物材料
✓ 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）