共查询到20条相似文献,搜索用时 15 毫秒
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Diane R Wagner Sonali Karnik Zachary J Gunderson Jeffery J Nielsen Alanna Fennimore Hunter J Promer Jonathan W Lowery M Terry Loghmani Philip S Low Todd O McKinley Melissa A Kacena Matthias Clauss Jiliang Li 《World journal of stem cells》2019,11(6):281-296
Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells(MSCs) are directed to replace the bone tissue, while endothelial progenitor cells(EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species,and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics.Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly. 相似文献
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Claudia Eberle 《Computer methods in biomechanics and biomedical engineering》2014,17(7):704-713
As a basis for model-based analysis of the processes in secondary fracture healing, a dynamical model is presented that characterises the physiological status in the fracture area by the location-dependent composition of tissues. Five types of tissue are distinguished: connective tissue, cartilage, bone, haematoma and avascular bone. A rule base is given that describes dynamical tissue differentiation processes. The rules consider not only a mechanical stimulus but also osteogenic and a vasculative factors as biological stimuli. Within this model structure, it is possible, e.g., to distinguish intramembranous from endochondral ossification processes. An objective function is introduced to assess accordance between the model-based simulation results and reference healing stages. By minimising this objective function, relevant tissue differentiation rates can be determined. For a reference process of secondary fracture healing it could be shown that the intramembranous ossification rate of 0.313%/day (from connective tissue to bone) is much smaller than the endochondral ossification rate of 1.136%/day (from cartilage to bone). In order to verify the model approach, it is transferred to simulate long bone distraction. Results show that healing patterns of bone distraction can be predicted. Using this method, it is possible to identify model parameters for individual subjects. This will allow a patient-specific analysis of tissue healing processes in future. 相似文献
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目的 观察四君子汤对骨损伤后小鼠免疫功能和细菌易位的影响,探讨中药在提高免疫力及预防感染方面的作用.方法 通过制备小鼠股骨骨损伤模型,骨损伤后在腹腔注射抗生素的同时辅以四君子汤,观察四君子汤对小鼠吞噬细胞功能的影响和细菌易位的控制.结果 骨损伤经四君子汤治疗后肝脏细菌易位明显减少(P<0.01);吞噬细胞功能显著增强(P<0.01);因有效控制了感染使骨修复过程加速.结论 四君子汤能够保护骨损伤后小鼠肠道细菌易位和促进骨修复. 相似文献
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Gelatinase A, also called matrix metalloproteinase 2 (MMP-2), belongs to the matrix metalloproteinase (MMP) family. MMP-2 cleaves type IV collagen, denatured collagen (gelatin), and other extracellular matrix (ECM) components. MMP-2 has been reported to be involved in a number of biological and pathological processes, but previous studies have not indicated that its expression is essential for early embryogenesis. In the current study, we have utilized zebrafish as a developmental model to study the role of MMP-2 during embryogenesis. We have successfully isolated a zebrafish MMP-2 (zMMP-2) homologue showing over 80% identity and over 90% similarity to its human counterpart. In situ analysis showed that zMMP-2 was expressed as early as the one-cell stage implying a maternal origin during oogenesis, and embryos continued to express zMMP-2 through at least the 72-h stage of development. RT-PCR analysis confirmed the in situ expression pattern and gelatin zymography indicated that a metalloproteinase with the same gel mobility as vertebrate MMP-2 was present in zebrafish embryos. Injection of zMMP-2 antisense morpholino oligonucleotides into 1- to 4-cell embryos resulted in a truncated axis, monitored through 72 h of development indicating that this metalloproteinase plays an important role in zebrafish embryogenesis. Monpholino-induced alterations in development began to be observed at 12 h of embryogenesis based on morphological and axis marker studies. The results obtained in zebrafish are in contrast to murine knockout studies that indicate that MMP-2 does not have a major role in mouse embryogenesis.Edited by D. Tautz 相似文献
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Matthias Haase Ishrath Ansurudeen Sven Schinner Iryna Paramonova Matthias Schott Claudia Papewalis Stefan R. Bornstein Werner A. Scherbaum Holger S. Willenberg 《Cell and tissue research》2009,336(2):337-343
The adrenal gland contains a well-organized network of blood vessels, and adrenocortical cells are situated in close proximity
to endothelial cells. Recently, several new mechanisms have been characterized that control the release of aldosterone by
adrenocortical cells, including the involvement of endothelial-cell-derived factors. Interestingly, a CBP/p300-interacting
transactivator with ED-rich tail 2 (CITED2), which is necessary for adrenal development, has been linked to aldosterone synthesis.
We have therefore examined the effects of endothelial-cell-conditioned medium (ECCM), as produced during the incubation of
human umbilical vein endothelial cells for 24 h, on the promoter activity and mRNA and protein expression of CITED2 in adrenocortical
cells as represented by the NCI-H295R cell line. We have found a dose-dependent effect of ECCM on CITED2 promoter activity;
this peaks at 480%. Activation of the CITED2 promoter occurs in parallel to an increase in CITED2 messenger RNA (as quantified
by real-time polymerase chain reaction) and protein. The stimulatory effect of ECCM can be reversed by blocking mitogen-activated
protein kinase activity with the MEK1-inhibitor PD98059. We conclude that products secreted by endothelial cells control not
only steroidogenesis, but also factors that are important for adrenocortical development, thereby highlighting the role of
cellular interactions within adrenocortical development and physiology.
This work was supported by a grant from the Doktor Robert Pfleger-Stiftung, Bamberg, Germany, to H.S.W. 相似文献
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Andreykiv A van Keulen F Prendergast PJ 《Biomechanics and modeling in mechanobiology》2008,7(6):443-461
Modelling the course of healing of a long bone subjected to loading has been the subject of several investigations. These
have succeeded in predicting the differentiation of tissues in the callus in response to a static mechanical load and the
diffusion of biological factors. In this paper an approach is presented which includes both mechanoregulation of tissue differentiation
and the diffusion and proliferation of cell populations (mesenchymal stem cells, fibroblasts, chondrocytes, and osteoblasts).
This is achieved in a three-dimensional poroelastic finite element model which, being poroelastic, can model the effect of
the frequency of dynamic loading. Given the number of parameters involved in the simulation, a parameter variation study is
reported, and final parameters are selected based on comparison with an in vivo experiment. The model predicts that asymmetric
loading creates an asymmetric distribution of tissues in the callus, but only for high bending moments. Furthermore the frequency
of loading is predicted to have an effect. In conclusion, a numerical algorithm is presented incorporating both mechanoregulation
and evolution of cell populations, and it proves capable of predicting realistic difference in bone healing in a 3D fracture
callus. 相似文献
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With a growing interest of the involvement of extracellular nucleotides in both normal physiology and pathology, it has become
evident that P2 receptor agonists and antagonists may have therapeutic potential. The P2Y2 receptor agonists (diquafosol tetrasodium
and denufosol tetrasodium) are in the phase 3 of clinical trials for dry eye and cystic fibrosis, respectively. The thienopyridine
derivatives clopidogrel and ticlopidine (antagonists of the platelet P2Y12 receptor) have been used in cardiovascular medicine
for nearly a decade. Purines and pyrimidines may be of therapeutic potential also in wound healing since ATP and UTP have
been shown to have many hallmarks of wound healing factors. Recent studies have demonstrated that extracellular nucleotides
take part in all phases of wound repair: hemostasis, inflammation, tissue formation, and tissue remodeling. This review is
focused on the potent purines and pyrimidines which regulate many physiological processes important for wound healing. 相似文献
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Masakazu Atobe Kenji Naganuma Masashi Kawanishi Takahiko Hayashi Hiroko Suzuki Masahiro Nishida Hirokazu Arai 《Bioorganic & medicinal chemistry letters》2018,28(14):2408-2412
We describe a medicinal chemistry approach to the discovery of a novel EP1 antagonist exhibiting high potency and good pharmacokinetics. Our starting point is 1, an EP1 receptor antagonist that exhibits pharmacological efficacy in cystometry models following intravenous administration. Despite its good potency in vitro, the high lipophilicity of 1 is a concern in long-term in vivo studies. Further medicinal chemistry efforts identified 4 as an improved lead compound with good in vitro ADME profile applicable to long term in vivo studies. A rat fracture study was conducted with 4 for 4?weeks to validate its utility in bone fracture healing. The results suggest that this EP1 receptor antagonist stimulates callus formation and thus 4 has potential for enhancing fracture healing. 相似文献
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In this study, we are successfully fabricated on a hydrogel consisting of TiO2 nanoparticles loaded onto a gelatin/chitosan matrix to control the acceleration of bone fracture healing and improved the nursing care applications. Each specimen (chitosan, gelatin and titanium dioxide) were characterized and confirmed by using different techniques, Fourier transforms infrared spectroscopy, X-ray diffraction analysis, Scanning Electron Microscopy with Elemental dispersive X-ray analysis, Thermo-gravimetric and Differential thermal analysis. In addition, the cell cytotoxicity results verified that the TiO2/gelatin-chitosan hydrogel are nontoxic to osteoblasts. And cell fixation outcome after 5 days of incubation condition revels that the enhanced in vitro cell survival and cell spreading on the prepared TiO2 incorporated hydrogel with respect to gelatin/chitosan hydrogel. Furthermore, TiO2/gelatin-chitosan hydrogel nanostructures can modulate the bone fracture healing, indicating a potential application on nursing care. 相似文献
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Influence of fracture gap size on the pattern of long bone healing: a computational study 总被引:4,自引:0,他引:4
Gómez-Benito MJ García-Aznar JM Kuiper JH Doblaré M 《Journal of theoretical biology》2005,235(1):105-119
Following fractures, bones restore their original structural integrity through a complex process in which several cellular events are involved. Among other factors, this process is highly influenced by the mechanical environment of the fracture site. In this study, we present a mathematical model to simulate the effect of mechanical stimuli on most of the cellular processes that occur during fracture healing, namely proliferation, migration and differentiation. On the basis of these three processes, the model then simulates the evolution of geometry, distributions of cell types and elastic properties inside a healing fracture. The three processes were implemented in a Finite Element code as a combination of three coupled analysis stages: a biphasic, a diffusion and a thermoelastic step. We tested the mechano-biological regulatory model thus created by simulating the healing patterns of fractures with different gap sizes and different mechanical stimuli. The callus geometry, tissue differentiation patterns and fracture stiffness predicted by the model were similar to experimental observations for every analysed situation. 相似文献
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Fracture repair is a complex process involving timed cellular recruitment, gene expression, and synthesis of compounds that regenerate native tissue to restore the mechanical integrity, and thus function of injured bone. While the majority of fractures heal without complication, this takes time and a subset of patients (~10%) experience healing delays, extending their morbidity and treatment costs. Consequently, there is a need for efficacious therapeutics for the intervention of fracture healing. Recent studies into the molecular control of fracture repair and advances in the understanding of the skeleton as a whole have resulted in the identification of numerous novel targets and compounds for such intervention. These include traditional agents such bone morphogenetic proteins and other growth factors, but also relatively newer compounds such as parathyroid hormone and modulators of the Wnt signaling pathway. These agents, along with others, are discussed in the current article in terms of their investigative status and potential for clinical implementation. Hopefully, these agents, as well as others yet to be discovered, will demonstrate sufficient clinical utility for successful intervention of fracture healing. This may have significant implications for the duration of morbidity and costs associated with traumatic bone fractures. J. Cell. Biochem. 109: 302–311, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
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Low intensity ultrasound stimulation has been used as a strategy to promote fracture healing. This study investigated the mechanism of ultrasound stimulation in enhancing fracture healing. Forty-five adult New Zealand White rabbits were divided into control, microwave treated, and ultrasound stimulation groups. After anesthesia, transverse osteotomy was created at midportion of the fibula bone. Intravital staining followed by fluorescence microscopic examination of new bone formation in the osteotomy site and biomechanical tests on torsional stiffness of the osteotomy site were performed. The difference between each examination was evaluated and analyzed. After ultrasound stimulation, new bone formation in the osteotomy site of the stimulated limb was 23.1-35.8% faster than that of the sham treated limb; the torsional stiffness of the stimulated limb was 44.4-80.0% higher than that of the sham treated limb. In the group of microwave hyperthermia treatment, the new bone formation was higher than that of the sham treated limb, but the difference was not statistically significant. The difference in torsional stiffness between the microwave hyperthermia treated limbs and the sham treated limb was not quite statistically significant. We demonstrated that low intensity ultrasound stimulation could increase the new bone formation and torsional stiffness. These effects probably are not mediated via hyperthermia. 相似文献
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One of the most damaging effects of reactive oxygen species (ROS) is lipid peroxidation, the end-product of which is malondialdehyde (MDA). This study was aimed to evaluate erythrocyte MDA levels during fracture healing in rats. Thirty male rats were used and the rats were divided into two groups to serve as controls and tests. Six rats were used as a control group that was not subject to fracture. The remaining 24 rats were divided into four groups and erythrocyte MDA levels were examined on days 5, 10, 20 and 30 post fracture. The right fibulas of rats were broken by manual angulation in the experimental group. The erythrocyte malondialdehyde level was measured in the experimental and control groups. The difference between malondialdehyde levels of control and experimental groups was statistically significant (p<0.05). Oxidative stress clearly increases during fracture healing in rats. 相似文献
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Rundle CH Strong DD Chen ST Linkhart TA Sheng MH Wergedal JE Lau KH Baylink DJ 《The journal of gene medicine》2008,10(3):229-241
BACKGROUND: An in vivo gene therapy strategy was developed to accelerate bone fracture repair. METHODS: Direct injection of a murine leukemia virus-based vector targeted transgene expression to the proliferating periosteal cells arising shortly after fracture. Cyclooxygenase-2 (Cox-2) was selected because the transgene for its prostaglandin products that promote angiogenesis, bone formation and bone resorption, are all required for fracture healing. The human (h) Cox-2 transgene was modified to remove AU-rich elements in the 3'-untranslated region and to improve protein translation. RESULTS: In vitro studies revealed robust and sustained Cox-2 protein expression, prostaglandin E(2) and alkaline phosphatase production in rat bone marrow stromal cells and osteoblasts transgenic for the hCox-2 gene. In vivo studies in the rat femur fracture revealed that Cox-2 transgene expression produced bony union of the fracture by 21 days post-fracture, a time when cartilage persisted within the fracture tissues of control animals and approximately 1 week earlier than the healing normally observed in this model. None of the ectopic bone formation associated with bone morphogenetic protein gene therapy was observed. CONCLUSIONS: This study represents the first demonstration that a single local application of a retroviral vector expressing a single osteoinductive transgene consistently accelerated fracture repair. 相似文献