ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Yajing Wang,Aoyun Li,Khalid Mehmood,Riaz Hussain,Rao Zahid Abbas,M. Tariq Javed,Yung-Fu Chang,Lianmei Hu,Jiaqiang Pan,Ying Li,Lijun Shi,Zhaoxin Tang,Hui Zhang
Long-term exposure to excessive fluoride causes chronic damage in the body tissues and could lead to skeletal and dental fluorosis. Cartilage damage caused by excessive fluoride intake has gained wide attention, but how fluoride accumulation blocks the development of chondrocytes is still unclear. Here, we report a negative correlation between the length and growth plate width after NaF treatments via apoptosis and autophagy, with shrinkage of cells, nuclear retraction, dissolution of chondrocytes. Whereas, fluoride exposure had no significant effect on the number and distribution of the osteoclasts which were well aligned. More importantly, fluoride exposure induced apoptosis of tibial bone through CytC/Bcl-2/P53 pathways via targeting Caspase3, Caspase9, Bak1, and Bax expressions. Meanwhile, the Beclin1, mTOR, Pakin, Pink, and p62 were elevated in NaF treatment group, which indicated that long-term excessive fluoride triggered the autophagy in the tibial bone and produced the chondrocyte injury. Altogether, fluoride exposure induced the chondrocyte injury by regulating the autophagy and apoptosis in the tibial bone of ducks, which demonstrates that fluoride exposure is a risk factor for cartilage development. These findings revealed the essential role of CytC/Bcl-2/P53 pathways in long-term exposure to fluoride pollution and block the development of chondrocytes in ducks, and CytC/Bcl-2/P53 can be targeted to prevent fluoride induced chondrocyte injury.
研究领域:
毒理学
·
细胞生物学
·
兽医学
✓ 已验证
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2021
·
IF 4.06
Jinlong Chen,Yishan Yang
Objective: To determine whether long-chain non-coding RNA (lncRNA) HAGLR can regulate BMP2 by absorbing microRNA-214-3p (miR-214-3p), and to explore its role and mechanism in tibial fracture (TF) healing. Methods: The HAGLR, miR-214-3p, and BMP2 expression levels in TF and in adjacent normal tissues were measured using quantitative real-time polymerase chain reaction (qRT-PCR). MC3T3-E1 osteoblasts were used to construct the in vitro model. HAGLR was localized subcellularly through RNA-fluorescence in situ hybridization (FISH). A dual-luciferase report experiment confirmed that miR-214-3p has a targeted relationship with HAGLR and BMP2. It was then divided into a HAGLR over-expression group, an miR-214-3p mimic group, a HAGLR+miR-214-3p mimic group, an sh-HAGLR group, a BMP over-expression group, an sh-HAGLR+over-expression BMP2 group, and a negative control group. The proliferation and apoptosis of the MC3T3-E1 osteoblasts were examined using MTT assays and flow cytometry. A TF model was established in male C57BL/6J mice. The serum alkaline phosphatase (ALP) and osteoprotegerin (OPG) levels in the sham group, the TF group, and the TF group that were injected with HAGLR were compared using ELISA. Hematoxylin-eosin (HE) staining was used to confirm the fracture healing in the mouse model. Results: Compared with the adjacent normal tissues in the TF patients, the HAGLR and BMP2 expressions decreased but the miR-214-3p expressions increased in the TF tissues ( P <0.05). HAGLR, an endogenous sponge, absorbed the miR-214-3p, and the BMP2 expression was directly regulated by miR-214-3p. HAGLR increased the proliferative activity of the osteoblasts and decreased the apoptosis rate. The over-expression of miR-214-3p partly reversed the effect of HAGLR on the cells, decreased the proliferative activity, and increased the apoptosis rate (all P <0.05). The sh-HAGLR decreased the proliferative activity and increased the apoptosis rate. But after the over-expression of BMP2, the proliferative activity of the cells was higher, and the apoptosis rate was lower than it was in the sh-HAGLR group (all P <0.05). The over-expression of HAGLR can up-regulate the ALP and OPG levels in mouse models ( P <0.05). Conclusion: lncRNA HAGLR can regulate BMP2 to play a protective role in TF by absorbing miR-214-3p, and it is related to promoting the osteoblast proliferation, inhibiting apoptosis, and up-regulating the serum ALP and OPG levels to accelerate bone healing.
研究领域:
分子生物学
·
骨科
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2022
·Vol. 36
·期 10
·e22530
·
IF 5.834
Chengyu Yang,Yang Liu,Ziyan Wang,Minmin Lin,Chao Liu
Despite the best treatment, approximately 10% of fractures still face undesirable repair and result in delayed unions or non-unions. Dynamic mechanical stimulation promotes bone formation, when applied at the correct time frame, with optimal loading magnitude, frequency, and repetition. Controlled mechanical loading significantly increases osteogenic cells during the matrix deposition phase of bone repair. In the bone defect, the blood vessel network guides the initial bone formation activities. A unique blood vessel subtype (Type H) exists in bone, which expresses high levels of CD31 and endomucin, and functions to couple angiogenesis and osteogenesis. However, how this form of controlled mechanical loading regulates the Type H vessels and promotes bone formation is still not clear. Sphingosine 1-phosphate (S1P) participates in the bone anabolic process and is a key regulator of the blood vessel. Its receptor, sphingosine 1-phosphate receptor 1 (S1Pr1), is a mechanosensitive protein that regulates vascular integrity. Therefore, we hypothesis that controlled anabolic mechanical loading promotes bone repair by acting on Type H vessels. To study the effect of S1Pr1 on loading induced-bone repair, we utilized a stabilized tibial defect model, which allows for the application of anabolic mechanical loading. Mechanical loading upregulated S1Pr1 within the entire defect, with up to 80% expressed in blood vessels, as observed by deep tissue imaging. Additionally, S1Pr1 antagonism by W146 inhibited the anabolic effects of mechanical loading. We showed that mechanical loading or activating S1Pr1 could induce YAP nuclear translocation, a key regulator in the cell's mechanical response, in endothelial cells (ECs) in vitro. Inhibition of S1Pr1 in endothelial cells by siRNA reduced loading-induced YAP nuclear translocation and expressions of angiogenic genes. In vivo, YAP nuclear translocation in Type H vessels was up-regulated after mechanical loading but was inhibited by antagonizing S1Pr1. S1Pr1 agonist, FTY720, increased bone volume and Type H vessel volume, similar to that of mechanical stimulation. In conclusion, controlled anabolic mechanical loading enhanced bone formation mainly through Type H vessels in a S1Pr1-dependent manner.
研究领域:
骨科
·
再生医学
·
生物力学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Yu Han,Li-Hui Sun,Bo Cai,Ming Xia,Chun-Quan Zhu,Dong-Song Li
Large bone defects are a major clinical challenge in bone reconstructive surgery. 3D printing is a powerful technology that enables the manufacture of custom tissue-engineered scaffolds for bone regeneration. Electrical stimulation (ES) is a treatment method for external bone defects that compensates for damaged internal electrical signals and stimulates cell proliferation and differentiation. In this study, we propose a simple, reliable, and versatile strategy to prepare multifunctional 3D printed scaffold combined with ES for bone defect therapy. Firstly, scaffolds composed of polycaprolactone (PCL) and Ti 3 C 2 were prepared by 3D printing technology, and then a stromal cell derived factor 1 (SDF1) containing DOPA tag was loaded onto the scaffold surface. Ti 3 C 2 was selected as the electrode component because of its excellent electrical conductivity. The selection of DOPA-modified SDF-1(DOPA-SDF1) can improve the material binding ability and exert long-term stem cell recruitment function. The results show that prepared 3D printed scaffold (DOPA-SDF1@PCL#Ti 3 C 2 ) has good hydrophilicity, electrical conductivity, antibacterial property, biocompatibility and stem cell recruitment ability. Furthermore, the expression of osteogenic specific genes in scaffold surface cells was significantly increased when pulse ES (PES) treatment was applied. The results of tibial plateau defect repair experiment showed that DOPA-SDF1@PCL#Ti 3 C 2 scaffold can significantly promote the formation of new bone and collagen fibres. When the DOPA-SDF1@PCL#Ti 3 C 2 scaffold was used in combination with PES therapy, the bone defect regeneration rate was further improved. This kind of scaffold could provide a new strategy for promoting the healing of large bone injuries and could expand the application of adjuvant therapy such as PES.
研究领域:
组织工程
·
生物材料
·
再生医学
·
生物医学工程
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Wenyi Wang,Junli Chang,Hongfeng Ruan,Xingyuan Sun,Fulai Zhao,Peng Zhao,Chujie Zhou,Junjie Tong,Suxia Guo,Qi Shi,Yongjun Wang,Weian Zhang,Yanping Yang
Cancer is a global leading cause of death, with nearly 10 million people dying from cancer in 2020. Photodynamic therapy (PDT) has emerged as a promising cancer treatment modality; however, the potential molecular mechanisms remain obscure. Herein, we designed a near-infrared (NIR) light-activated nanoplatform (TPBC-PEG) to explore the therapeutic effects and mechanisms of PDT by using a model of intratibial primary and pulmonary metastasis osteosarcoma. Under laser irradiation, TPBC-PEG photosensitizer dose-dependently inhibited proliferative and metastatic capabilities while promoting apoptosis of osteosarcoma cells in vitro, and also effectively suppressed carcinogenesis and pulmonary metastasis in osteosarcoma xenograft mouse model. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis after high-throughput mRNA-seq indicated that the HIPPO signaling pathway was one of the 20 most significantly related signaling pathways. And a series of experiments for determining the HIPPO signaling activity were conducted to reconfirm the specificity. Collectively, PDT of TPBC-PEG micelles against carcinogenesis and pulmonary metastasis of deep-seated intratibial osteosarcoma was achieved by activating HIPPO signaling pathway. Our study identified a hitherto uncharacterized molecular mechanism of PDT, which may provide new insights to understand and design promising nanoplatforms for future cancer therapies.
研究领域:
肿瘤学
·
分子生物学
·
治疗学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 9
·3614-3626
·
IF 5.251
Yihong Gong,Yiling Zhang,Zhinan Cao,Feng Ye,Zefeng Lin,Yan Li
Injectable scaffolds have attracted much attention because of their minimum surgical invasiveness. However, limited osteogenic induction property and low mechanical properties hampered their application in bone tissue engineering. CaCO3 microspheres, which possess osteoinductivity, rough surfaces and specific binding sites for BMP-2, were first fabricated; after BMP-2 uploading, microspheres were further entrapped in fibrin-glue hydrogel. CaCO3 microspheres were co-functionalized with casein and heparin. To obtain a high encapsulation of heparin and thus BMP-2 uploading, along with controlled release and simultaneous maintenance of the presence of vaterite which had osteogenic induction property, fabrication parameters were optimized and microspheres were characterized using XRD, FITR and SEM. The formed CaCO3 had a microsphere morphology of ∼1 μm. Both vaterite and calcite phases were present and the relative amount of calcite phase increased with the amount of heparin. Sample 25 mM_4-1Hep with the highest loading amount of heparin was selected as carrier for BMP-2 and BMP-2 loaded CaCO3 microspheres were further entrapped in fibrin-glue hydrogel (FC-B). For the as-prepared composite hydrogel, mechanical properties were characterized and the presence of CaCO3 significantly elevated the tensile strength; controlled release of BMP-2 was sustained until day 21. Based on ALP activity, alizarin red staining and RT-PCR, in vitro osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was found to be significantly enhanced under induction of FC-B. Rabbit tibia bone defect model was applied to evaluate its in vivo performance. After implantation for 4 weeks, presence of composite hydrogel was observed in defects. After 8 weeks, bone defects of FC-B group were nearly completely healed. Using the fact that autologous scaffolds can be derived based on fibrin-glue hydrogel, the well-designed BMP-2 loaded fibrin-glue composite hydrogel demonstrated good potential in bone tissue engineering.
研究领域:
组织工程
·
生物材料
·
骨再生
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Animal Models and Experimental Medicine
·
2024
·
IF 3.8
Bing Zhang,Tingting Fu,Yi Han,Gongke Li,Xianyao Wan,Yong Li
Backgroud Thoracic Trauma and Limb Fractures Are the Two most Common Injuries in Multiple Trauma. However, there Is Still a Lack of Mouse Models of Trauma Combining Tibial Shaft Fracture (TSF) and Thoracic Trauma. In this Study, we Attempted to Develop a Novel Mouse Model of TSF Combined with Blunt Chest Trauma (BCT). Methods A total of 84 C57BL/6J male mice were used as the multiple trauma model. BCT was induced by hitting the chests of mice with heavy objects, and TSF was induced by hitting the tibia of mice with heavy objects after intramedullary fixation. Serum specimens of mice were received by cardiac puncture at defined time points of 0, 6, 12, 24, 48, and 72 h. Results Body weight and body temperature tended to decrease within 24 h after multiple trauma. Hemoglobin analyses revealed a decrease during the first 24 h after multiple trauma. Some animals died by cardiac puncture immediately after chest trauma. These animals exhibited the most severe pulmonary contusion and hemorrhage. The level of lung damage varied in diverse mice but was apparent in all animals. Classic hematoxylin and eosin (H&E)-stained paraffin pulmonary sections of mice with multiple trauma displayed hemorrhage and an immunoinflammatory reaction. Bronchoalveolar lavage fluid (BALF) and serum samples of mice with multiple trauma showed an upregulation of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-1 α (TNF-1 α ) compared with the control group. Microimaging confirmed the presence of a tibia fracture and pulmonary contusion. Conclusions The novel mouse multiple trauma model established in this study is a common trauma model that shows similar pathological mechanisms and imaging characteristics in patients with multiple injuries. This study is useful for determining whether blockade or intervention of the cytokine response is beneficial for the treatment of patients with multiple trauma. Further research is needed in the future.
研究领域:
创伤外科
·
免疫学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Jinfeng Liao,Kun Shi,Yanpeng Jia,Yanting Wu,Zhiyong Qian
Osteosarcoma is a malignant bone tumor, which often occurs in adolescents. However, surgical resection usually fails to completely remove the tumor clinically, which has been the main cause of postoperative recurrence and metastasis, resulting in the high death rate of patients. At the same time, osteosarcoma invades a large area of the bone defect, which cannot be self-repaired and seriously affects the life quality of the patients. Herein, a bifunctional methacrylated gelatin/methacrylated chondroitin sulfate hydrogel hybrid gold nanorods (GNRs) and nanohydroxyapatite (nHA), which possessed excellent photothermal effect, was constructed to eradicate residual tumor after surgery and bone regeneration. In vitro , K7M2wt cells (a mouse bone tumor cell line) can be efficiently eradicated by photothermal therapy of the hybrid hydrogel. Meanwhile, the hydrogel mimics the extracellular matrix to promote proliferation and osteogenic differentiation of mesenchymal stem cells. The GNRs/nHA hybrid hydrogel was capable of photothermal treatment of postoperative tumors and bone defect repair in a mice model of tibia osteosarcoma. Therefore, the hybrid hydrogel possesses dual functions of tumor therapy and bone regeneration, which shows great potential in curing bone tumors and provides a new hope for tumor-related bone complex disease.
研究领域:
生物材料
·
癌症治疗
·
组织工程
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2021
·
IF 6.4
Chun Liu,Wen Qin,Yan Wang,Jiayi Ma,Jun Liu,Siyu Wu,Hongbin Zhao
Introduction Bone tissue engineering (BTE) is a new strategy for bone defect repair, but the difficulties in the fabrication of scaffolds with personalized structures still limited their clinical applications. The rapid development in three-dimensional (3D) printing endows it capable of controlling the porous structures of scaffolds with high structural complexity and provides flexibility to meet specific needs of bone repair. Methods In this study, sodium alginate (SA)/gelatin (Gel) hydrogel scaffolds doped with different contents of nano-attapulgite were fabricated via 3D printing. The surface microstructure, hydrophilicity and mechanical properties were fully evaluated. Furthermore, mouse bone marrow-derived mesenchymal stem cells (BMSCs) were cultured with the composite hydrogels in vitro, and proliferation and osteoblastic differentiation were assessed. A rabbit tibia plateau defect model was used to evaluate the osteogenic potential of the composite hydrogel in vivo. Results When increasing nano-ATP content, the Gel/SA/nano-ATP composite hydrogels showed better mechanical property and printability. Moreover, Gel/SA/nano-ATP composite hydrogels showed excellent bioactivity, and a significant mineralization effect was observed on the surface after being incubated in simulated body fluid (SBF) for 14 days. The Gel/SA/nano-ATP composite hydrogel also showed good biocompatibility and promoted the osteogenesis of BMSCs. Finally, histological analysis demonstrates that the Gel/SA/nano-ATP composite hydrogels could effectively enhance bone regeneration in vivo. Conclusion These properties render the Gel/SA/nano-ATP composite hydrogel scaffolds an ideal bone tissue engineering material for the repair of bone defects.
研究领域:
生物医学工程
·
组织工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 99
·97096-97106
·
IF 3.289
Ning Cui,Junmin Qian,Jinlei Wang,Yaping Wang,Weijun Xu,Hongjie Wang
Polypeptides synthesized from α-amino acid N-carboxyanhydrides are considered ideal candidates as scaffold materials for bone tissue engineering due to their excellent biocompatibility and non-toxic degradation products. However, undesirable mechanical properties and osteoinductivity restrict their application in bone healing and regeneration. To overcome these limitations, we modified a synthetic polypeptide poly(Nε-Cbz-L-lysine) (PZL) with poly(lactic-co-glycolic acid) (PLGA) having relatively high strength and osteoinductive bioglass (BG) particles, and fabricated foamy PZL/PLGA/BG composite scaffolds using a negative NaCl-templating method. The morphology, compression modulus, thermal and degradation behaviors of the PZL/PLGA/BG composite scaffolds were characterized, and the in vitro biocompatibility was evaluated with MC3T3-E1 cells using live/dead staining, MTT and ALP assays. The results indicated that the PZL/PLGA/BG composite scaffold with a weight ratio of 5 : 5 : 1 (PZL5PLGA5BG) had higher compression modulus and protein adsorption and mineralization abilities than other scaffolds, and was more conducive to the adhesion, proliferation and osteoblastic differentiation of MC3T3-E1 cells. The in vivo biocompatibility of the scaffolds was evaluated in both rat subcutaneous model and rabbit tibia defect model. The results of histological studies of subcutaneous implants, as confirmed by H&E, Masson's trichrome and CD34 staining assays, demonstrated that the PZL5PLGA5BG composite scaffolds allowed the ingrowth of tissue and microvessels and exhibited reduced inflammation response as compared to other scaffolds after 8 weeks of implantation. In experimental studies in bone defect model, the results of digital radiography and H&E staining confirmed that the PZL5PLGA5BG composite scaffolds after 8 weeks of implantation significantly improved in vivo osteogenesis. The newly formed bone tissue grew into the scaffolds along with the degradation of the materials. To sum up, the foamy PZL/PLGA/BG composite scaffolds had good comprehensive performances and would meet the needs of bone regeneration.
研究领域:
生物医学工程
·
材料科学
·
组织工程
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2023
·
IF 17.1
Mengzhen Zhang,Xinyun Zhai,Tengfei Ma,Yongkang Huang,Mengdie Jin,Houzhi Yang,Hao Fu,Shuai Zhang,Tianwei Sun,Xin Jin,Yaping Du,Chun-Hua Yan
Rational design of multifunctional biomaterials with customized architecture and on demand bioactivity is of great significance for bone tissue engineering (BTE) in modern society. Herein, a versatile therapeutic platform has been established by integrating cerium oxide nanoparticles (CeO2 NPs) into bioactive glass (BG) to fabricate three-dimensional (3D)-printed scaffolds, achieving a sequential therapeutic effect against inflammation and promoting osteogenesis toward bone defect. The antioxidative activity of CeO2 NPs plays a crucial role in alleviating the oxidative stress upon formation of bone defects. Subsequently, CeO2 NPs exert a promotion effect on the proliferation and osteogenic differentiation of rat osteoblasts through enhancing mineral deposition and alkaline phosphatase and osteogenic gene expression. Strikingly, the incorporation of CeO2 NPs bestows on the BG scaffolds greatly reinforced mechanical properties, improved biocompatibility, adequate cell adhesion, elevated osteogenic capability, and multifunctional performance in a single platform. In vivo studies on the treatment of rat tibial defect confirmed the better osteogenic properties of CeO2–BG scaffolds compared with pure BG scaffolds. Additionally, the employment of the 3D printing technique creates a proper porous microenvironment around the bone defect, which further facilitates the cell in-growth and new bone formation. This report provides a systematic study on CeO2–BG 3D-printed scaffolds prepared by simple ball milling method, achieving sequential and integral treatment in BTE based on a single platform.
研究领域:
材料科学
·
生物医学工程
·
组织工程
·
纳米技术
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2023
·
IF 13.1
Hao Zhang,Li Li,Lei Chu,Jing Huang,Xiaochen Chen,Xianglong Zhuo,Yulin Wang,John Robert Honiball,Bin Wang,Wei Chen,William W. Lu,Deping Wang,Bing Li,Xu Cui,Haobo Pan
Effective treatment of osteomyelitis remains to be clinical challenge due to the recurrent and persistent nature of the disease. Studies have shown that borate glasses can serve as implants for local drug delivery in treating osteomyelitis, as well as aid in regenerating bone defects in vivo . However, both the kinetics of drug release from borate glass-based implants and the underlying molecular mechanism for promoting bone regeneration remain unclear. Here, delivery implants with varying amounts of antibiotics were fabricated by encapsulating gentamicin sulfate (GS) into a chitosan glue and applying it to borosilicate glass (BSG). Upon immersion in phosphate buffered saline (PBS), delivery implants degraded and converted into hydroxyapatite (HA). All delivery implants released GS sustainably over a period of around 25 days in both PBS and K2HPO4 solutions and displayed efficacious inhibition of E. coli and S. aureus in vitro. GS release occurred through diffusion for inhibition whereby Fickian diffusion was revealed to be the predominant release kinetic. Ions (B, Ca, P and Si) released from BSG supported the proliferation, differentiation, osteogenic gene expression and protein secretion of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. When implanted in a rabbit tibial osteomyelitis model, osteomyelitis in the experimental group with delivery implants was effectively cured. Meanwhile, delivery implants have significant osteogenesis-promoting effects after implantation time of 12-weeks in vivo . Implantation of BSG-based drug delivery implants developed in this study may provide a promising method for treating osteomyelitis as well as for facilitating efficient bone regeneration.
研究领域:
材料科学
·
生物医学工程
·
药学
·
再生医学
✓ 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）