scholarly journals Three-Dimensionally Printed Ti2448 With Low Stiffness Enhanced Angiogenesis and Osteogenesis by Regulating Macrophage Polarization via Piezo1/YAP Signaling Axis

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhen Tang ◽  
Xinghui Wei ◽  
Tian Li ◽  
Hao Wu ◽  
Xin Xiao ◽  
...  
Keyword(s):  
Bone Repair ◽  
Macrophage Polarization ◽  
Stress Shielding ◽  
Biological Properties ◽  
Future Application ◽  
M2 Macrophages ◽  
Low Elastic Modulus ◽  
Signaling Axis

Previous studies have found that the novel low-elastic-modulus Ti2448 alloy can significantly reduce stress shielding and contribute to better bone repair than the conventional Ti6Al4V alloy. In this study, the promotion of osteogenesis and angiogenesis by three-dimensionally printed Ti2448 were also observed in vivo. However, these were not significant in a series of in vitro tests. The stiffness of materials has been reported to greatly affect the response of macrophages, and the immunological regulation mediated by macrophages directly determines the fate of bone implants. Therefore, we designed more experiments to explore the role of three-dimensionally printed Ti2448 in macrophage activation and related osteogenesis and angiogenesis. As expected, we found a significant increase in the number of M2 macrophages around Ti2448 implants, as well as better osteogenesis and angiogenesis in vivo. In vitro studies also showed that macrophages pre-treated with Ti2448 alloy significantly promoted angiogenesis and osteogenic differentiation through increased PDGF-BB and BMP-2 secretion, and the polarization of M2 macrophages was enhanced. We deduced that Ti2448 promotes angiogenesis and osteogenesis through Piezo1/YAP signaling axis-mediated macrophage polarization and related cytokine secretion. This research might provide insight into the biological properties of Ti2448 and provide a powerful theoretical supplement for the future application of three-dimensionally printed Ti2448 implants in orthopaedic surgery.

scholarly journals TMIC-51. GBP1 RECRUITS MACROPHAGES TO PROMOTE GLIOBLASTOMA GROWTH

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi259-vi259
Author(s):  
Lili Chen ◽  
Ming Li
Keyword(s):  
Macrophage Polarization ◽  
Tumor Development ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Orthotopic Mouse Model ◽  
Ccl2 Expression ◽  
Molecule Inhibitor ◽  
Signaling Axis ◽  
And Migration

Abstract Guanylate binding protein 1 (GBP1) is an interferon-inducible large GTPase which plays a key role in tumor development, but the molecular mechanism is poorly understood. Here we investigated whether GBP1 could influence the tumor microenvironment in glioblastoma, the most common and malignant brain tumor. We found that forced expression of GBP1 in glioblastoma cells induced macrophage polarization toward an M2 phenotype via upregulating Chemokine (C-C motif) ligand 2 (CCL2). CCL2 acted via its receptor C-C chemokine receptor 2 (CCR2) to enhance macrophage cell migration in vitro. The M2 macrophages in turn promoted glioblastoma cell proliferation and migration. The orthotopic mouse model showed that GBP1 recruited M2 macrophages into tumor to promote glioblastoma progression, and targeting CCL2/CCR2 signaling axis with a small molecule inhibitor RS504393 led to decreased macrophage attraction and M2 polarization and a significant tumor growth retardation and prolonged survival of tumor-bearing mice. Clinically, GBP1 expression positively correlated with M2 macrophage numbers and CCL2 expression in glioblastoma. Taken together, our results reveal that GBP1 modulates the tumor immune microenvironment through CCL2 induction to promote glioblastoma infiltrating growth, and targeting tumor-associated macrophages may represent a new therapeutic strategy against glioblastoma.

scholarly journals Effect of silicon-doped calcium phosphate cement on angiogenesis based on controlled macrophage polarization

2021 ◽  
Author(s):  
Soomin Lee ◽  
Zheng Li ◽  
Dehua Meng ◽  
Qinming Fei ◽  
Libo Jiang ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Calcium Phosphate Cement ◽  
Bone Repair ◽  
Macrophage Polarization ◽  
Calvarial Bone ◽  
Inflammatory Phase ◽  
Endothelial Proliferation ◽  
Silicon Doped

Abstract Vascularization is an important early indicator of osteogenesis involving biomaterials. Bone repair and new bone formation are associated with extensive neovascularization. Silicon-based biomaterials have attracted widespread attention due to their rapid vascularization. Although calcium phosphate cement (CPC) is a mature substitute for bone, the application of CPC is limited by its slow degradation and insufficient promotion of neovascularization. Calcium silicate (CS) has been shown to stimulate vascular endothelial proliferation. Thus, CS may be added to CPC (CPC–CS) to improve the biocompatibility and neovascularization of CPC. In the early phase of bone repair (the inflammatory phase), macrophages accumulate around the biomaterial and exert both anti- and pro-inflammatory effects. However, the effect of CPC–CS on macrophage polarization is not known, and it is not clear whether the effect on neovascularization is mediated through macrophage polarization. In the present study, we explored whether silicon-mediated macrophage polarization contributes to vascularization by evaluating the CPC–CS-mediated changes in the immuno-environment under different silicate ion contents both in vivo and in vitro. We found that the silicon released from CPC–CS can promote macrophage polarization into the M2 phenotype and rapid endothelial neovascularization during bone repair. Dramatic neovascularization and osteogenesis were observed in mouse calvarial bone defects implanted with CPC–CS containing 60% CS. These findings suggest that CPC–CS is a novel biomaterial that can modulate immune response, promote endothelial proliferation, and facilitate neovascularization and osteogenesis. Thus, CPC–CS shows potential as a bone substitute material.

scholarly journals Montelukast, a Cysteinyl Leukotriene Receptor 1 Antagonist, Induces M2 Macrophage Polarization and Inhibits Murine Aortic Aneurysm Formation

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yohei Kawai ◽  
Yuji Narita ◽  
Aika Yamawaki-Ogata ◽  
Akihiko Usui ◽  
Kimihiro Komori
Keyword(s):  
Aortic Aneurysm ◽  
Macrophage Polarization ◽  
Enzyme Linked Immunosorbent Assay ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Gene Expressions ◽  
Arginase 1 ◽  
M2 Macrophage Polarization

Background. The pathogenesis of abdominal aortic aneurysm (AAA) is characterized by atherosclerosis with chronic inflammation in the aortic wall. Montelukast is a selective cys-LT 1 receptor antagonist that can suppress atherosclerotic diseases. We evaluated the in vitro properties of montelukast and its in vivo activities in an angiotensin II–infused apolipoprotein E–deficient (apoE−/−) AAA mouse model. Methods. The mouse monocyte/macrophage cell line J774A.1 was used in vitro. M1 macrophages were treated with montelukast, and gene expressions of inflammatory cytokines were measured. Macrophages were cultured with montelukast, then gene expressions of arginase-1 and IL (interleukin)-10 were assessed by quantitative polymerase chain reaction, arginase-1 was measured by fluorescence-activated cell sorting, and IL-10 concentration was analyzed by enzyme-linked immunosorbent assay. In vivo, one group (Mont, n=7) received oral montelukast (10 mg/kg/day) for 28 days, and the other group (Saline, n=7) was given normal Saline as a control for the same period. Aortic diameters, activities of matrix metalloproteinases (MMPs), cytokine concentrations, and the number of M2 macrophages were analyzed. Results. Relative to control, montelukast significantly suppressed gene expressions of MMP-2, MMP-9, and IL-1β, induced gene expressions of arginase-1 and IL-10, enhanced the expression of the arginase-1 cell surface protein, and increased the protein concentration of IL-10. In vivo, montelukast significantly decreased aortic expansion (Saline vs Mont; 2.44 ± 0.15 mm vs 1.59 ± 0.20 mm, P<.01), reduced MMP-2 activity (Saline vs Mont; 1240 μM vs 755 μM, P<.05), and induced infiltration of M2 macrophages (Saline vs Mont; 7.51 % vs 14.7 %, P<.05). Conclusion. Montelukast induces M2 macrophage polarization and prevents AAA formation in apoE−/− mice.

scholarly journals Hexapeptide induces M2 macrophage polarization via the JAK1/STAT6 pathway to promote angiogenesis in bone repair

2021 ◽  
Author(s):  
Xinyun Han ◽  
Junxian Hu ◽  
Wenbo Zhao ◽  
Hongwei Lu ◽  
Jingjin Dai ◽  
...  
Keyword(s):  
Bone Repair ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Promising Alternative ◽  
Defect Repair ◽  
M2 Macrophage Polarization ◽  
Underlying Mechanisms ◽  
Main Regulator

Abstract Angiogenesis is essential for successful bone defect repair. In normal tissue repair, the physiological inflammatory response is the main regulator of angiogenesis through the activity of macrophages and the cytokines secreted by them. In particular, M2 macrophages which secrete high levels of PDGF-BB are typically considered to promote angiogenesis. A hexapeptide [WKYMVm, (Trp-Lys-Tyr-Met-Val-D-Met-NH2)] has been reported to modulate inflammatory activities. However, the underlying mechanisms by which WKYMVm regulates macrophages remain unclear. In this study, the possible involvement by which WKYMVm induces the polarization of macrophages and affects their behaviors was evaluated. In vitro results showed that macrophages were induced to an M2 rather than M1 phenotype and the M2 phenotype was enhanced by WKYMVm through activation of the JAK1/STAT6 signaling pathway. It was also found that WKYMVm played an important role in the PDGF-BB production increase and proangiogenic abilities in M2 macrophages. Consistent with the results in vitro, the elevated M2/M0 ratio induced by WKYMVm enhanced the formation of new blood vessels in a femoral defect mouse model. In summary, these findings suggest that WKYMVm could be a promising alternative strategy for angiogenesis in bone repair by inducing M2 macrophage polarization.

scholarly journals Hexapeptide induces M2 macrophage polarization via the JAK1/STAT6 pathway to promote angiogenesis in bone repair

2021 ◽  
Author(s):  
Xinyun Han ◽  
Junxian Hu ◽  
Wenbo Zhao ◽  
Hongwei Lu ◽  
Jingjin Dai ◽  
...  
Keyword(s):  
Bone Repair ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Promising Alternative ◽  
Defect Repair ◽  
M2 Macrophage Polarization ◽  
Underlying Mechanisms ◽  
Main Regulator

Angiogenesis is essential for successful bone defect repair. In normal tissue repair, the physiological inflammatory response is the main regulator of angiogenesis through the activity of macrophages and the cytokines secreted by them. In particular, M2 macrophages which secrete high levels of PDGF-BB are typically considered to promote angiogenesis. A hexapeptide [WKYMVm, (Trp-Lys-Tyr-Met-Val-D-Met-NH2)] has been reported to modulate inflammatory activities. However, the underlying mechanisms by which WKYMVm regulates macrophages remain unclear. In this study, the possible involvement by which WKYMVm induces the polarization of macrophages and affects their behaviors was evaluated. In vitro results showed that macrophages were induced to an M2 rather than M1 phenotype and the M2 phenotype was enhanced by WKYMVm through activation of the JAK1/STAT6 signaling pathway. It was also found that WKYMVm played an important role in the PDGF-BB production increase and proangiogenic abilities in M2 macrophages. Consistent with the results in vitro, the elevated M2/M0 ratio induced by WKYMVm enhanced the formation of new blood vessels in a femoral defect mouse model. In summary, these findings suggest that WKYMVm could be a promising alternative strategy for angiogenesis in bone repair by inducing M2 macrophage polarization.

scholarly journals Angelicin Alleviates Post-Trauma Osteoarthritis Progression by Regulating Macrophage Polarization via STAT3 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhansong Tian ◽  
Fanchun Zeng ◽  
Chunrong Zhao ◽  
Shiwu Dong
Keyword(s):  
Side Effects ◽  
Macrophage Polarization ◽  
Critical Factor ◽  
Molecular Medicine ◽  
M2 Macrophages ◽  
Stat3 Pathway ◽  
M2 Polarization ◽  
Ifn Γ

Post-trauma osteoarthritis (PTOA) is the most common articular disease characterized by degeneration and destruction of articular cartilage (Bultink and Lems, Curr. Rheumatol Rep., 2013, 15, 328). Inflammatory response of local joint tissue induced by trauma is the most critical factor accelerating osteoarthritis (OA) progression (Sharma et al., 2019; Osteoarthritis. Cartilage, 28, 658–668). M1/M2 macrophages polarization and repolarization participates in local inflammation, which plays a major role in the progression of OA (Zhang et al., 2018; Ann. Rheum. Dis., 77, 1524–1534). The regulating effect of macrophage polarization has been reported as a potential therapy to alleviate OA progression. Synovitis induced by polarized macrophages could profoundly affect the chondrocyte and cartilage matrix (Zhang et al., 2018; Ann. Rheum. Dis., 77, 1524–1534). Generally, anti-inflammatory medications widely used in clinical practice have serious side effects. Therefore, we focus on exploring a new therapeutic strategy with fewer side effects to alleviate the synovitis. Angelicin (ANG) is traditional medicine used in various folk medicine. Previous studies have revealed that angelicin has an inhibitory effect on inflammation (Wei et al., 2016; Inflammation, 39, 1876–1882), tumor growth (Li et al., 2016; Oncology reports, 36, 3,504–3,512; Wang et al., 2017; Molecular Medicine Reports, 16, 5441–5449), DNA damage (Li et al., 2019; Exp. Ther. Med., 18, 1899–1906), and virus proliferation (Li et al., 2018; Front. Cell. Infect. Microbiol., 8, 178). But its specific effects on influencing the process of OA were rarely reported. In this study, the molecular mechanism of angelicin in vivo and in vitro was clearly investigated. Results showed that angelicin could regulate the M1/M2 ratio and function and alleviate the development of PTOA in the meanwhile. Bone marrow monocytes were isolated and induced by macrophage colony-stimulating factor (M-CSF), lipopolysaccharide (LPS) and interferon (IFN)-γ for M1 polarization and interleukin (IL)-4/IL-13 for M2 polarization. Subsequently, repolarization intervention was performed. The results indicate that angelicin can repolarize M1 toward M2 macrophages by upregulating the expression of CD9. Besides, angelicin can also protect and maintain M2 polarization in the presence of LPS/IFN-γ, and subsequently downregulate the expression of inflammatory mediators such as IL-1β and TNF-α. Mechanistically, angelicin can activate the p-STAT3/STAT3 pathway by conducting CD9/gp130 to repolarize toward M2 macrophages. These results suggest angelicin can alleviate the progression of OA by regulating M1/M2 polarization via the STAT3/p-STAT3 pathway. Therefore, angelicin may have a promising application and potential therapeutic value in OA clinical treatment.

scholarly journals Melittin Regulates Iron Homeostasis as a Key Mediator of Macrophage Polarization in Rat Lumbar Spinal Stenosis

2021 ◽  
Author(s):  
Hyunseong Kim ◽  
Jin Young Hong ◽  
Wan-Jin Jeon ◽  
Junseon Lee ◽  
Yoon Jae Lee ◽  
...  
Keyword(s):  
Spinal Stenosis ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Macrophage Polarization ◽  
M2 Macrophages ◽  
Iron Release ◽  
Locomotor Recovery ◽  
Lumbar Spinal

Abstract BackgroundLumbar spinal stenosis (LSS) is defined as the narrowing of the spinal canal, which compresses the nerves traveling through the lower back into the legs. Inflammation is the most common cause of LSS. Chronic pain induced by nerve damage results from chronic inflammation, and the inflammation response worsens with elevated iron stores. Furthermore, macrophage polarization to the M1 (inflammatory) or M2 (anti-inflammatory) type is essential for controlling host defense or repairing tissues. However, the precise function of macrophage polarization in iron release or retention in LSS pathophysiology is not well-understood. Here, we introduce melittin to modulate macrophage polarization related to iron metabolism for LSS treatment.MethodsPrimary peritoneal macrophage were cultured in 200 or 500 ng/mL of melittin and FeSO4-containing medium for 24 h. Macrophage polarization was assessed by Immunofluorescence staining to CD86 or Arg1 antibodies. In an in vivo rat model of LSS, melittin were administered at 100 and 250 µg/kg, and in vivo effects of melittin on iron deposition-induced macrophage polarization was evaluated by immunochemistry, real time-PCR, western blot, and flow-cytometry. The locomotor functions were assessed by BBB, ladder scoring, and Von Frey test for up to 3 weeks. ResultsIn vitro experiments demonstrated that macrophages can be polarized toward an M2 phenotype after melittin treatment in iron-insulted primary macrophages. Treatment with 100 and 250 μg/kg melittin in a rat LSS model increased the proportion of M2 macrophages in the damaged spinal cord. Moreover, we found that melittin attenuated iron overload-induced M1 polarization via regulating iron metabolism-related genes in LSS rats. As a result, melittin improved locomotor recovery and stimulated axonal growth following LSS.ConclusionsMelittin can promote functional recovery in LSS models by activating M2 macrophages via controlling macrophage iron metabolism, suggesting the potential applications of melittin for treating LSS.

Nanodrugs as a new approach in therapy of cardiovascular diseases and cancer with tumor-associated angiogenesis

2020 ◽  
Vol 28 ◽  
Author(s):  
Justyna Hajtuch ◽  
Karolina Niska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Controlled Drug Release ◽  
Biological Properties ◽  
Comprehensive Information ◽  
Conventional Drug ◽  
Key Factor ◽  
Functionalized Materials

Background: Cancer along with cardiovascular diseases are globally defined as leading causes of death. Importantly, some risk factors are common to these diseases. The process of angiogenesis and platelets aggregation are observed in cancer development and progression. In recent years, studies have been conducted on nanodrugs in these diseases that have provided important information on the biological and physicochemical properties of nanoparticles. Their attractive features are that they are made of biocompatible, well-characterized and easily functionalized materials. Unlike conventional drug delivery, sustained and controlled drug release can be obtained by using nanomaterials. Methods: In this article, we review the latest research to provide comprehensive information on nanoparticle-based drugs for the treatment of cancer, cardiovascular disease associated with abnormal haemostasis, and the inhibition of tumorassociated angiogenesis. Results: The results of the analysis of data based on nanoparticles with drugs confirm their improved pharmaceutical and biological properties, which gives promising antiplatelet, anticoagulant and antiangiogenic effects. Moreover, the review included in vitro, in vivo research and presented nanodrugs with chemotherapeutics approved by Food and Drug Administration. Conclusion: By the optimization of nanoparticles size and surface properties, nanotechnology are able to deliver drugs with enhanced bioavailability in treatment of cardiovascular disease, cancer and inhibition of cancer-related angiogenesis. Thus, nanotechnology can improve the therapeutic efficacy of the drug, but there is a need for a better understanding of the nanodrugs interaction in the human body, because this is a key factor in the success of potential nanotherapeutics.

Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

2019 ◽  
Vol 20 (4) ◽  
pp. 285-292 ◽  
Author(s):  
Abdullah M. Alnuqaydan ◽  
Bilal Rah
Keyword(s):  
Medicinal Plant ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
In Vivo Model ◽  
Drug Candidate ◽  
Phytochemical Analysis ◽  
Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

scholarly journals 99mTc Labelling Strategies for the Development of Potential Nitroimidazolic Hypoxia Imaging Agents

Inorganics ◽  
2019 ◽  
Vol 7 (11) ◽  
pp. 128 ◽  
Author(s):  
Giglio ◽  
Rey
Keyword(s):  
Rational Design ◽  
Biological Properties ◽  
Fine Tuning ◽  
Oxidation States ◽  
Hypoxia Imaging ◽  
Biological Target ◽  
99Mtc Radiopharmaceuticals ◽  
99Mtc Labelling

Technetium-99m has a rich coordination chemistry that offers many possibilities in terms of oxidation states and donor atom sets. Modifications in the structure of the technetium complexes could be very useful for fine tuning the physicochemical and biological properties of potential 99mTc radiopharmaceuticals. However, systematic study of the influence of the labelling strategy on the “in vitro” and “in vivo” behaviour is necessary for a rational design of radiopharmaceuticals. Herein we present a review of the influence of the Tc complexes’ molecular structure on the biodistribution and the interaction with the biological target of potential nitroimidazolic hypoxia imaging radiopharmaceuticals presented in the literature from 2010 to the present. Comparison with the gold standard [18F]Fluoromisonidazole (FMISO) is also presented.

Sign in / Sign up

Export Citation Format

Share Document