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1.
Orthop Surg ; 2021 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-33818004

RESUMEN

OBJECTIVE: To study the curative effect of bionic tiger-bone powder on osteoporosis in ovariectomized rats and investigate its mechanism. METHODS: Overall, a 120 female Wistar rats were randomly divided into Sham (sham-operated group), ovariectomy (OVX, ovariectomized group), TB (bionic tiger-bone powder treatment group after ovariectomy) and TB + VD groups (bionic tiger-bone powder + vitamin D treatment group after ovariectomy). The osteoporotic rat model was established 3 months after ovariectomy, and rats were intragastrically administrated with the corresponding drugs. Serum and bone tissue samples were collected from 10 rats in each group at weeks 4, 12 and 24 after intragastric administration. The bone microstructure of L6 vertebrae was analyzed by MicroCT, the biomechanical strength of left femurs was measured by the three-point bending test, and serum bone metabolism markers (P1NP and CTX) were detected by ELISA. Changes in bone collagen were analyzed by Masson's trichrome staining and hydroxyproline detection, and members of the BMP2/SMAD/RUNX2 and OPG/RANKL/RANK signal pathways were detected by immunoblotting. RESULTS: Compared with the OVX group, the serum level of P1NP in the TB and TB + VD groups was higher (P < 0.05), while the CTX level was lower (P < 0.05). Bone collagen fiber structures in the TB and TB + VD groups were repaired, and the collagen content was significantly higher than that in the OVX group (P < 0.05). In the TB group, BMP-2, P-SMAD1/5, RUNX2 and OPG levels were increased in bone tissue (P < 0.01), RANKL levels were decreased (P < 0.01), and the bone microstructure and biomechanical strength were improved. CONCLUSION: Bionic tiger-bone powder promotes osteogenesis by activating the BMP2/SMAD/RUNX2 signaling pathway, suppresses osteoclasts by downregulating the OPG/RANK/RANKL signaling pathway, increases bone collagen content, and improves bone microstructure and bone biomechanical strength.

2.
Sci Total Environ ; 770: 144756, 2021 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-33513503

RESUMEN

The saltmarsh plant Spartina alterniflora was introduced to the Jiangsu coasts, China and serves as an ecological engineer to reduce near-bed shear stress, trap fine-grained sediments and protect the coast from wave-induced erosion. The saltmarshes thus could record the Spartina colonization-driven changes within the sedimentary layers. Based on these ecological and sedimentological changes in sediments, we present a new eco-parametric method to estimate the sedimentation rate for the newly-formed wetlands in the Yancheng Wetland Nature Reserve for Rare Birds, Jiangsu. Sediment cores and satellite imagery were used to identify the thickness of accumulated sediment layers and the time since the Spartina colonization. We defined the original ground on which Spartina alterniflora initially colonized using pigment concentrations, grain size and stable carbon isotopic compositions of organic matter (δ13C) in sediments. We also determined the time mark of the Spartina colonization by examining the Landsat images over 1982-2018 to discriminate the Spartina alterniflora from other native plants and geomorphological features. These two datasets yielded a sedimentation rate of 3.3 cm/yr for Core A and of 9.6 cm/yr for Core B, the latter evidenced by an increase of ~ 0.51 m in the bed level from 2008 to 2014. Combining the 210Pb dating method, we further estimated the sedimentation rate for the layers beneath the original ground, which was comparable to that of the bare flats in the Jiangsu coast. Even though this new method is only applicable to newly-formed saltmarshes, it helps identify the recent sedimentation events as well as reveal the environmental changes and the evolution of saltmarsh-bare flat systems due to the interplay between vegetation, hydrodynamics and sediment dynamics. It thus could be an efficient and cost-effective tool for an improved understanding of the response of coastal wetlands to a changing climate/environment.

3.
Life Sci ; : 118680, 2020 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-33130075

RESUMEN

AIMS: Osteoporosis is considered a common skeletal disease. Ortho-silicic acid has been found to enhance the osteogenic differentiation of osteoblasts. However, the molecular mechanism of osteogenesis induced by ortho-silicic acid is still undefined totally. MicroRNAs (miRs) play a key role in osteogenesis of osteoblasts. This study investigated the role of miR-130b in promoting osteogenesis induced by ortho-silicic acid. MAIN METHODS AND KEY FINDINGS: In this study, we found ortho-silicic acid enhanced osteogenesis of osteoblasts in vitro and promoted preventing and treating osteoporosis in vivo. Furthermore, the expression of miR-130b increased under application of ortho-silicic acid. In vitro, experiments demonstrated miR-130b overexpression or inhibition significantly promoted or suppressed osteogenic differentiation of osteoblasts under application of ortho-silicic acid, respectively. Consistently, downregulation of miR-130b in ovariectomy (OVX) rats dropped off the beneficial effect of ortho-silicic acid against bone loss. Mechanistically, we identified phosphatase and tensin homologue deleted on human chromosome 10 (PTEN) as the direct target of miR-130b during osteogenesis induced by ortho-silicic acid. SIGNIFICANCE: In conclusion, our findings reveal that ortho-silicic acid promotes the osteogenesis of osteoblasts mediated by the miR-130b/PTEN signaling axis, which identifies a new target to prevent and treat osteoporosis.

4.
Drug Des Devel Ther ; 14: 4451-4463, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33122889

RESUMEN

Purpose: Glucocorticoids are used for the treatment of inflammatory diseases, but glucocorticoid treatment is associated with bone damage. Resveratrol is a phytoalexin found in many plants, and we investigated its protective role on dexamethasone-induced dysfunction in MC3T3-E1 cells and primary osteoblasts. Materials and Methods: MC3T3-E1 cells and primary osteoblasts were treated with dexamethasone in the presence/absence of different doses of resveratrol for 24 or 48 h. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium (MTT) and lactate dehydrogenase (LDH) assays were used to evaluate cell viability. Apoptosis was analyzed by a flow cytometry. An alkaline phosphatase (ALP) activity assay and Alizarin Red S staining were used to study osteoblast differentiation. Expression of osteoblast-related genes was measured by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The AMP-activated protein kinase (AMPK) signaling pathway and mitochondrial expression of superoxide dismutase were evaluated by Western blotting. Intracellular reactive oxygen species (ROS), adenosine triphosphate (ATP) content, mitochondrial-complex activity, and mitochondrial DNA content were measured to evaluate mitochondrial function. Results: Resveratrol induced the proliferation and inhibited apoptosis of osteoblasts in the presence of dexamethasone. Resveratrol increased the ALP activity and mineralization of osteoblasts. Resveratrol also attenuated dexamethasone-induced inhibition of mRNA expression of osteogenesis maker genes, including bone morphogenetic protein-2, osteoprotegerin, runt-related transcription factor-2, and bone Gla protein. Resveratrol alleviated dexamethasone-induced mitochondrial dysfunction. Resveratrol strongly stimulated expression of peroxisome proliferator-activated receptor-γ coactivator 1α and sirtuin-3 genes, as well as their downstream target gene superoxide dismutase-2. Resveratrol induced phosphorylation of AMPK and acetyl-CoA carboxylase (ACC). Blockade of AMPK signaling using compound C reversed the protective effects of resveratrol against dexamethasone. Conclusion: Resveratrol showed protective effects against dexamethasone-induced dysfunction of osteoblasts by activating AMPK signaling.

5.
Biol Trace Elem Res ; 2020 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-32893332

RESUMEN

The original version of this article unfortunately contained a mistake. The name of "Yunzhen Chen" is now corrected in the author group.

6.
Medicine (Baltimore) ; 99(29): e20954, 2020 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-32702835

RESUMEN

BACKGROUND: To investigate the risk factors for postoperative venous thromboembolism (VTE) in patients undergoing spinal surgery. METHODS: Literature published in PubMed, Embase, the Cochrane Library, and Web of Science was systematically reviewed to assess risk factors for VTE following spinal surgery. The data analysis was conducted with STATA 12.0. Data were pooled using fixed-effects or random-effects models according to the heterogeneity among the included studies. RESULTS: Twenty-six studies involving 3,216,187 patients were included in this meta-analysis, and the total incidence of VTE after spinal surgery was 0.35% (0.15-29.38%). The pooled analysis suggested that the incidence of VTE after spinal surgery was higher in such aspects as increasing age (weighted mean difference [WMD] 0.55 years, 95% confidence interval [CI] 0.33-0.78, P < .001), female sex (odds ratio [OR] 1.12, 95% CI 1.01-1.25; P = .034), diabetes (OR 1.34, 95% CI 1.29-1.44; P < .001), chronic kidney disease (OR = 8.31, 95% CI 1.98-34.93; P = .004), nonambulatory preoperative activity status (OR 3.67, 95% CI 2.75-4.83; P < .001), D-dimer level (WMD 1.023, 95% CI 0.162-1.884; P = .02), long duration of operation (WMD 0.73, 95% CI 0.21-1.24; P = .006), spine fusion (OR 1.54, 95% CI 1.31-1.82; P < .001), and blood transfusion (OR 2.31, 95% CI 1.73-3.07; P < .001), and the differences were statistically significant. However, there were no significant differences in body mass index, obesity, hypertension, coronary heart disease, spondylolisthesis, intraoperative blood loss, surgical procedures (anterior lumbar interbody fusion vs posterior intervertebral fusion /translaminar lumbar interbody fusion), or surgical site (lumbar vs thoracic) (all P > .05). CONCLUSION: Based on our meta-analysis, we identified several important factors that increased the risk of VTE after spinal surgery. We hope our study provides assistance to spine surgeons so that they can adequately analyze and assess risk factors in patients and then develop preventive measures to reduce the incidence of VTE.


Asunto(s)
Procedimientos Neuroquirúrgicos/efectos adversos , Procedimientos Ortopédicos/efectos adversos , Columna Vertebral/cirugía , Tromboembolia Venosa/etiología , Factores de Edad , Transfusión Sanguínea , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Limitación de la Movilidad , Tempo Operativo , Complicaciones Posoperatorias , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo , Factores Sexuales
7.
J Coll Physicians Surg Pak ; 30(6): 584-589, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32703341

RESUMEN

OBJECTIVE: To verify whether Scheuermann's disease (SD) is a risk factor for patients with recurrent lumbar disc herniation (rLDH) than in patients without recurrence. STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Department of Orthopaedics, Yantaishan Hospital, China, from December 2016 to September 2019. METHODOLOGY: The demographics (age, gender, body mass index [BMI], alcohol abuse, and current smoking), diabetes mellitus, and radiological data (affected levels, herniated side, herniation type, Pfirrmann grade, and the presence of SD) of 602 patients were retrospectively analysed, who underwent surgery for symptomatic LDH from December 2016 to August 2018. They were underwent one-year follow-up and were divided into LDH and rLDH groups. Both typical and atypical SD criteria were used to diagnose SD. Independent-sample t-test was used to analyse the role of age and BMI in both groups, and the Chi-square test was conducted to analyse other parameters. Logistic regression analysis was performed to evaluate various factors. RESULTS: There was a significant difference in age (p=0.026), BMI (p=0.007), current smoking (p=0.001), and SD (p<0.001) between the groups. When these parameters were included in the logistic regression analysis, age, current smoking status, and SD were found to be risk factors for rLDH. CONCLUSION: Age, current smoking, and SD are risk factors for rLDH. Older patients with radiological characteristics of SD should quit smoking to prevent rLDH. Key Words: Scheuermann's disease, Kyphosis, Disc herniation, Recurrence, Age, Smoking, Risk factor.

8.
Int Orthop ; 44(10): 2079-2087, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32676780

RESUMEN

PURPOSE: This prospective, stratified, randomized, single-blind, placebo-controlled multicentre study investigated the safety and effectiveness of reducing blood loss and preventing venous thromboembolism (VTE) during posterior lumbar interbody fusion (PLIF) in patients with stenosis or spondylolisthesis using the combination of tranexamic acid (TXA) and rivaroxaban. METHODS: The Autar score was evaluated in patients after admission. Patients with an Autar score ≤ 10 were randomized to group A or B. Group A was the placebo-controlled group. Patients in group B were treated with 1 g TXA via intravenous injection and 1 g TXA for external use. Patients with an Autar score > 10 were randomized to group C or D. Patients in group C were treated with 10-mg rivaroxaban qd for 35 days after surgery. Patients in group D received the same treatment as those in group B intra-operatively and as those in group C post-operatively. RESULTS: A total of 599 patients from eight hospitals participated in this clinical trial. The total blood loss, intra-operative blood loss, and drainage volume were reduced by the administration of TXA (group A vs group B, P < 0.01; group C vs group D, P < 0.01), and the blood transfusion rate was also decreased (group A vs group B, P < 0.01; group C vs group D, P < 0.01). There were no significant differences (P > 0.05) in the VTE incidence rates among group A and group B. In patients with high-risk thrombosis, the number of patients with VTE was only three and seven after the application of rivaroxaban. Epidural haematoma was not discovered in any patients in our trial. CONCLUSION: The combined application of tranexamic acid and rivaroxaban significantly reduced the amount of blood loss and the transfusion rate during PLIF surgery and avoided an increase in the probability of thrombosis and the occurrence of epidural haematoma. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ChiCTR-1800016430 2018-06-01.

9.
Biol Trace Elem Res ; 2020 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-32676940

RESUMEN

Numerous experiments in vitro and in vivo have shown that an appropriate increase intake of silicon can facilitate the synthesis of collagen and its stabilization and promote the differentiation and mineralization of osteoblasts. In this study, we examined whether ortho-silicic acid restrains the differentiation of osteoclast through the receptor activator of nuclear factor κB ligand (RANKL)/receptor activator of nuclear factor κB (RANK)/osteoprotegerin (OPG) signaling pathway by investigating its effect in vitro and in vivo. Bone marrow macrophage (BMM) cells were isolated and cultured with or without ortho-silicic acid, and then TRAP staining and immunofluorescence were performed to detect the differentiation of osteoclast. The RANKL-induced osteoclast marker gene and protein expression including c-Fos, nuclear factor of activated T cells cl (NFATcl), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B P50 (NF-κB P50), NF-κB P52, RANK, integrin ß3, cathepsin K (CTSK), DC-STAMP, and TRAP were quantitatively detected by western blot and RT-PCR. Ovariectomized (OVX) rats were injected with ortho-silicic acid (OVX+Si group) and normal saline (OVX group), and sham-operated rats were injected with normal saline (Sham group). And micro-CT, H&E, and TRAP staining, ELISA, and western blot were performed. Ortho-silicic acid could inhibit the differentiation of osteoclast, and the marker genes and proteins were decreased. The OVX-induced bone loss could be reversed by ortho-silicic acid. Our finding demonstrated that ortho-silicic acid suppresses RANKL-induced osteoclastogenesis and has potential value as a therapeutic agent for OVX-induced bone loss.

10.
Onco Targets Ther ; 13: 2173-2181, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32210583

RESUMEN

Objective: Circular RNA is a newly discovered non-coding RNA. It plays an important role in regulating gene expression, and may take part in tumor progression. This study aimed to investigate the functions of hsa_circ_0008792 in osteosarcoma regulation. Methods: We identified a circular RNA, hsa_circ_0008792, by using bioinformatics to analyze the GSE96962 dataset. The capacities of migration and invasion were assessed by wound-healing assay and transwell Matrigel assay. The ratios of G0/G1, S, and G2/M phases in cell cycle and apoptosis were measured using flow cytometry. Results: Hsa_circ_0008792 is expressed at low levels in osteosarcoma cells, and up-regulation of hsa_circ_0008792 could suppress osteosarcoma cell migration and invasion and promote apoptosis. This regulation is mediated by hsa-miR-711/ZFP1. The expression level of hsa_circ_0008792 showed no influence on cell cycle of osteosarcoma cells. Conclusion: Osteosarcoma is suppressed by hsa_circ_0008792/hsa-miR-711/ZFP1 axis.

11.
Stem Cell Res Ther ; 11(1): 38, 2020 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-31992369

RESUMEN

BACKGROUND: As important players in cell-to-cell communication, exosomes (exo) are believed to play a similar role in promoting fracture healing. This study investigated whether exosomes derived from bone marrow mesenchymal stem cells (BMMSC-Exos) could improve fracture healing of nonunion. METHODS: BMMSC-Exos were isolated and transplanted into the fracture site in a rat model of femoral nonunion (Exo group) every week. Moreover, equal volumes of phosphate-buffered saline (PBS) and exosome-depleted conditioned medium (CM-Exo) were injected into the femoral fracture sites of the rats in the control and CM-Exo groups. Bone healing processes were recorded and evaluated by radiographic methods on weeks 8, 14 and 20 after surgery. Osteogenesis and angiogenesis at the fracture sites were evaluated by radiographic and histological methods on postoperative week 20. The expression levels of osteogenesis- or angiogenesis-related genes were evaluated in vitro by western blotting and immunohistochemistry. The ability to internalize exosomes was assessed using the PKH26 assay. Altered proliferation and migration of human umbilical vein endothelial cells (HUVECs) and mouse embryo osteoblast precursor cells (MC3TE-E1s) treated with BMMSC-Exos were determined by utilizing EdU incorporation, immunofluorescence staining, and scratch wound assay. The angiogenesis ability of HUVECs was evaluated through tube formation assays. Finally, to explore the effect of exosomes in osteogenesis via the BMP-2/Smad1/RUNX2 signalling pathway, the BMP-2 inhibitors noggin and LDN193189 were utilized, and their subsequent effects were observed. RESULTS: BMMSC-Exos were observed to be spherical with a diameter of approximately 122 nm. CD9, CD63 and CD81 were expressed. Transplantation of BMMSC-Exos obviously enhanced osteogenesis, angiogenesis and bone healing processes in a rat model of femoral nonunion. BMMSC-Exos were taken up by HUVECs and MC3T3-E1 in vitro, and their proliferation and migration were also improved. Finally, experiments with BMP2 inhibitors confirmed that the BMP-2/Smad1/RUNX2 signalling pathway played an important role in the pro-osteogenesis induced by BMMSC-Exos and enhanced fracture healing of nonunion. CONCLUSIONS: Our findings suggest that transplantation of BMMSC-Exos exerts a critical effect on the treatment of nonunion by promoting osteogenesis and angiogenesis. This promoting effect might be ascribed to the activation of the BMP-2/Smad1/RUNX2 and the HIF-1α/VEGF signalling pathways.

12.
Pathol Res Pract ; 216(2): 152766, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31796334

RESUMEN

OBJECTIVES: The aim of this study was to investigate the effect of Toll like receptor 4 (TLR4) on fracture healing. METHODS: The open tibial fracture models in TLR4 knockout (TLR4-/-) and wild type (WT) C57BL-6 J mice were established. The radiological examination, tartrate-resistant acid phosphatase (TRAP) staining, Micro-CT scan and biological torsion test were performed on 7, 14 and 21 days after operation. Enzyme Linked Immunosorbent Assay (ELISA) kit was used to detect the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß) and interleukin 6 (IL-6). Western blotting was used to detect the expression of ß-catenin, Wingless-type MMTV integration site family, member 4 and 5B (Wnt4 and Wnt5B), proliferating cell nuclear antigen (PCNA) and bone morphogenetic protein-2 (BMP-2) of the callus tissue obtained from mice. RESULTS: TLR4 knockout promoted fracture healing, reduced the number of osteoclasts, increased bone callus volume (BV) and callus mineralized volume fraction (BV/TV%) (P < 0.05), increased the maximum torque and torsional stiffness of callus (P < 0.05), reduced TNF-α, IL-1ß and IL-6 expression (P < 0.01), and increased the expression levels of ß-catenin, Wnt4, Wnt5B, PCNA and BMP-2 (P < 0.01). CONCLUSION: TLR4 knockout reduced inflammatory and promoted fracture healing by activating Wnt/ß-catenin signaling pathway.

13.
Braz J Med Biol Res ; 52(12): e8735, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31826179

RESUMEN

Exosomes, a kind of extracellular vesicle, are promising therapeutic agents for spinal cord injury (SCI). This article aimed to investigate effects of exosomes secreted from miRNA-29b-modified bone marrow mesenchymal stem cells (BMSCs) on SCI. Exosomes were extracted from BMSCs transfected with miRNA-29b or negative control (miR NC). SCI rats were injected intravenously with exosomes (control exosomes, miRNA-29b exosomes) and BMSCs (miR NC, miRNA-29b) through the tail vein. The expression of miRNA-29b in spinal cord tissues of SCI rats was detected by qRT-PCR. The hind limb motor function was evaluated by Basso Beattie Bresnahan (BBB) score. The histopathological damage and neuronal regeneration in spinal cord tissues was observed by HE staining and immunohistochemistry, respectively. The injection of miRNA-29b exosomes and miRNA-29b BMSCs both significantly increased the expression of miRNA-29b in spinal cord tissues of SCI rats (P<0.05). Compared with SCI rats, rats in the miRNA-29b exosomes and the miRNA-29b groups exhibited improved SCI, including increased BBB score, NF200 and GAP-43 positive neurons, as well as decreased contractile nerve cell numbers and GFAP positive neurons (all P<0.05). The relieving degree of SCI was significantly higher in the miRNA-29b exosomes group than in the miRNA-29b BMSCs group (P<0.05). Exosomes secreted from miRNA-29b-modified BMSCs were effective in the repair of SCI in rats.


Asunto(s)
Exosomas/metabolismo , Trasplante de Células Madre Mesenquimatosas , MicroARNs/metabolismo , Recuperación de la Función , Traumatismos de la Médula Espinal/terapia , Transfección , Animales , Modelos Animales de Enfermedad , Femenino , Inmunohistoquímica , Masculino , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
14.
Cell Transplant ; 28(11): 1373-1383, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31423807

RESUMEN

Severe spinal cord injury (SCI) is caused by external mechanical injury, resulting in unrecoverable neurological injury. Recent studies have shown that exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) might be valuable paracrine molecules in the treatment of SCI. In this study, we designed SCI models in vivo and in vitro and then investigated the possible mechanism of successful repair by BMSCs-Exos. In vivo, we established one Sham group and two SCI model groups. The Basso, Beattie, Bresnahan (BBB) scores showed that BMSCs-Exos could effectively promote the recovery of spinal cord function. The results of the Nissl staining, immunohistochemistry, and TUNEL/NeuN/DAPI double staining showed that BMSCs-Exos inhibited neuronal apoptosis. Western blot analysis showed that the protein expression level of Bcl-2 was significantly increased in the BMSCs-Exos group compared with the PBS group, while the protein expression levels of Bax, cleaved caspase-3, and cleaved caspase-9 were significantly decreased. The results of western bolt and qRT-PCR demonstrated that BMSCs-Exos could activate the Wnt/ß-catenin signaling pathway effectively. In vitro, we found that inhibition of the Wnt/ß-catenin signaling pathway could promote neuronal apoptosis following lipopolysaccharide (LPS) induction. These results demonstrated that BMSCs-Exos may be a promising therapeutic for SCI by activating the Wnt/ß-catenin signaling pathway.


Asunto(s)
Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Traumatismos de la Médula Espinal/terapia , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Caspasas/metabolismo , Células Cultivadas , Exosomas/ultraestructura , Lipopolisacáridos/toxicidad , Locomoción/fisiología , Masculino , Células Madre Mesenquimatosas/ultraestructura , Neuronas/citología , Neuronas/metabolismo , Neuronas/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/genética , Proteína X Asociada a bcl-2/metabolismo
15.
Life Sci ; 228: 208-214, 2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31055087

RESUMEN

AIMS: Current study aimed to investigate the effects of lncRNA SNHG1 on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explore the underlying mechanisms. MAIN METHODS: Mouse model of osteoporosis was created by ovariectomy (OVX). The BMD of mice spine, the serum level of ß-CTX and the ALP activity were measured. The expression of SNHG1, JNK, p-JNK, p-38, p-p38 and Osterix were examined by qRT-PCR and Western blot. Co-IP assay was used to verify the effect of SNHG1 on the interaction between p-p38 and Nedd4. Ubiquitination assay was used to evaluate the roles of SNHG1 in ubiquitination of p-p38. KEY FINDINGS: In the mice with osteoporosis, BMD was decreased and ß-CTX concentration and SNHG1 expression were increased. ALP activity and p-p38 protein level were elevated and SNHG1 expression was down-regulated in BMSCs stimulated by osteogenic inducer, while the effects were reversed by SNHG1 over-expression. SNHG1 over-expression enhanced the interaction between Nedd4 and p-p38, disrupted protein stability of p-p38, and promoted the ubiquitination of p-p38. In addition, pcDNA-SNHG1 down-regulated p-p38 protein level, and sh-Nedd4 removed the trend. Nedd4 silencing elevated ALP activity and Osterix protein level, while p-38 inhibitor abrogated the effects. In vivo, SNHG1 silence increased BMD and Osterix protein level, and decreased endogenous SNHG1 expression in mice with OVX. SIGNIFICANCE: This study proved the regulation mechanism that lncRNA SNHG1 negatively regulates p38 MAPK signal pathway through ubiquitination mediated by Nedd4, and thus inhibits osteogenic differentiation of BMSCs.


Asunto(s)
Células Madre Mesenquimatosas/citología , Ubiquitina-Proteína Ligasas Nedd4/metabolismo , Osteogénesis , Osteoporosis/genética , ARN Largo no Codificante/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Diferenciación Celular , Línea Celular , Femenino , Regulación de la Expresión Génica , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Ratones , Osteoporosis/metabolismo , Osteoporosis/patología , ARN Largo no Codificante/metabolismo , Transducción de Señal , Ubiquitinación
17.
Cell Transplant ; 28(7): 893-906, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31012325

RESUMEN

Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) are promising graft materials for cell therapies in spinal cord injury (SCI) models. Previous studies have demonstrated that MSCs can regulate the microenvironment of NSCs and promote their survival rate. Furthermore, several studies indicate that MSCs can reduce stem cell transplantation-linked tumor formation. To our knowledge, no previous studies have determined whether co-transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and human neural stem cells (hNSCs) could improve the outcome in rats with SCI. Therefore, we investigated whether the transplantation of hUC-MSCs combined with hNSCs through an intramedullary injection can improve the outcome of rats with SCI, and explored the underlying mechanisms. In this study, a moderate spinal cord contusion model was established in adult female Wistar rats using an NYU impactor. In total, 108 spinal cord-injured rats were randomly selected and divided into the following five groups: 1) hUC-MSCs group, 2) hNSCs group, 3) hUC-MSCs+hNSCs group, 4) PBS (control) group, and 5) a Sham group. Basso, Beattie and Bresnahan (BBB) behavioral test scores were used to evaluate the motor function of all animals before and after the SCI weekly through the 8th week. Two weeks after transplantation, some rats were sacrificed, immunofluorescence and immunohistochemistry were performed to evaluate the survival and differentiation of the transplanted stem cells, and brain-derived neurotrophic factor (BDNF) was detected by ELISA in the injured spinal cords. At the end of the experiment, we evaluated the remaining myelin sheath and anterior horn neurons in the injured spinal cords using Luxol Fast Blue (LFB) staining. Our results demonstrated that the surviving stem cells in the hUC-MSCs+hNSCs group were significantly increased compared with those in the hUC-MSCs alone and the hNSCs alone groups 2 weeks post-transplantation. Furthermore, the results of the BBB scores and the remaining myelin sheath evaluated via LFB staining in the injured spinal cords demonstrated that the most significantly improved outcome occurred in the hUC-MSCs+hNSCs group. The hUC-MSCs alone and the hNSCs alone groups also had a better outcome compared with that of the PBS-treated group. In conclusion, the present study demonstrates that local intramedullary subacute transplantation of hUC-MSCs, hNSCs, or hUC-MSCs+hNSCs significantly improves the outcome in an in vivo moderate contusion SCI model, and that co-transplantation of hUC-MSCs and hNSCs displayed the best outcome in our experiment.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/citología , Células-Madre Neurales/citología , Traumatismos de la Médula Espinal/terapia , Cordón Umbilical/citología , Animales , Diferenciación Celular/fisiología , Femenino , Humanos , Ratas , Ratas Wistar
18.
Biol Trace Elem Res ; 190(2): 327-335, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30421162

RESUMEN

Silicon is one of the essential trace elements in the human body; the deficiency of which may lead to bone diseases. Numerous animal experiments have shown that an appropriate increase in the intake of silicon is beneficial to enhancing bone density and toughness to prevent osteoporosis. However, the molecular mechanisms of the silicon-mediated osteogenesis process have not been sufficiently clarified. In this study, we determined the possible osteogenesis-related mechanisms of orthosilicic acid at a molecular level. We detected the relevant pathway and osteogenic indicators by immunofluorescence (IF), Western blot, alkaline phosphatase (ALP) staining (using 5-bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium [BCIP/NBT]), ALP enzyme labeling method, osteocalcin (OCN), and N-terminal propeptide of type 1 procollagen (P1NP) enzyme-linked immunosorbent assay (ELISA). We found that orthosilicic acid is capable of enhancing the expression of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), phospho-protein kinase B (P-Akt), phospho-mammalian target of rapamycin (P-mTOR), and related osteogenic markers (runt-related transcription factor 2 [RUNX2], type I collagen [COL1], ALP, OCN, and P1NP). However, with the addition of PI3K-Akt-mTOR pathway-specific inhibitor LY294002, the expression of PI3K, P-Akt, P-mTOR, RUNX2, COL1, ALP, OCN, and P1NP decreased. The results indicated that the PI3K-Akt-mTOR pathway played a positive regulatory role in the process of orthosilicic acid-mediated osteogenesis in vitro.


Asunto(s)
Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Ácido Silícico/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Osteoblastos/metabolismo , Silicio/farmacología , Relación Estructura-Actividad , Células Tumorales Cultivadas
19.
Braz. j. med. biol. res ; 52(12): e8735, 2019. graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1055473

RESUMEN

Exosomes, a kind of extracellular vesicle, are promising therapeutic agents for spinal cord injury (SCI). This article aimed to investigate effects of exosomes secreted from miRNA-29b-modified bone marrow mesenchymal stem cells (BMSCs) on SCI. Exosomes were extracted from BMSCs transfected with miRNA-29b or negative control (miR NC). SCI rats were injected intravenously with exosomes (control exosomes, miRNA-29b exosomes) and BMSCs (miR NC, miRNA-29b) through the tail vein. The expression of miRNA-29b in spinal cord tissues of SCI rats was detected by qRT-PCR. The hind limb motor function was evaluated by Basso Beattie Bresnahan (BBB) score. The histopathological damage and neuronal regeneration in spinal cord tissues was observed by HE staining and immunohistochemistry, respectively. The injection of miRNA-29b exosomes and miRNA-29b BMSCs both significantly increased the expression of miRNA-29b in spinal cord tissues of SCI rats (P<0.05). Compared with SCI rats, rats in the miRNA-29b exosomes and the miRNA-29b groups exhibited improved SCI, including increased BBB score, NF200 and GAP-43 positive neurons, as well as decreased contractile nerve cell numbers and GFAP positive neurons (all P<0.05). The relieving degree of SCI was significantly higher in the miRNA-29b exosomes group than in the miRNA-29b BMSCs group (P<0.05). Exosomes secreted from miRNA-29b-modified BMSCs were effective in the repair of SCI in rats.

20.
Neural Regen Res ; 12(9): 1538-1543, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29090001

RESUMEN

Dedifferentiation of Schwann cells is an important feature of the response to peripheral nerve injury and specific negative myelination regulators are considered to have a major role in this process. However, most experiments have focused on the distal nerve stump, where the Notch signaling pathway is strongly associated with Schwann cell dedifferentiation and repair of the nerve. We observed the phenotypic changes of Schwann cells and changes of active Notch signaling on the proximal stump during peripheral nerve repair using small gap conduit tubulization. Eighty rats, with right sciatic nerve section of 4 mm, were randomly assigned to conduit bridging group and control group (epineurium suture). Glial fibrillary acidic protein expression, in myelinating Schwann cells on the proximal stump, began to up-regulate at 1 day after injury and was still evident at 5 days. Compared with the control group, Notch1 mRNA was expressed at a higher level in the conduit bridging group during the first week on the proximal stump. Hes1 mRNA levels in the conduit bridging group significantly increased compared with the control group at 3, 5, 7 and 14 days post-surgery. The change of the Notch intracellular domain shared a similar trend as Hes1 mRNA expression. Our results confirmed that phenotypic changes of Schwann cells occurred in the proximal stump. The differences in these changes between the conduit tubulization and epineurium suture groups correlate with changes in Notch signaling. This suggests that active Notch signaling might be a key mechanism during the early stage of neural regeneration in the proximal nerve stump.

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