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1.
Langmuir ; 40(23): 12191-12199, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38814134

RESUMO

It is of great significance to construct a Z-scheme heterojunction for improving solar light harvesting and achieving efficient separation of photogenerated carriers and then enhancement of the photocatalytic performance of semiconductor photocatalysts. Herein, the direct Z-scheme PI/Ag2WO4 heterojunction was designed and prepared according to the band edge potentials of the semiconductor. Due to the fact that the Z-scheme structure not only endowed the PI/Ag2WO4 composites with efficient separation of photogenerated electron-hole pairs but also reserved the redox ability of the valence band and conduction band of monophase catalysts, the 50% PI/Ag2WO4 heterojunction exhibited excellent photocatalytic activity, which were 2.9 and 1.5 times those of the PI and Ag2WO4 photocatalysts, respectively. The photocatalytic reaction mechanism of PI/Ag2WO4 composites was confirmed by the results of TEM, UV-vis, XPS, and EPR experiments. This work provides a feasible strategy to design high-performance photocatalysts in the field of practice purification of wastewater.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38713871

RESUMO

BACKGROUND: The next-generation sequencing (NGS) has developed rapidly in the past decade and is becoming a promising diagnostic tool for periprosthetic infection (PJI). However, its diagnostic value for PJI is still uncertain. The purpose of this systematic review and meta-analysis was to evaluate the diagnostic value of NGS compared to culture. METHODS: In this systematic review and meta-analysis, electronic databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and clinicaltrials.gov were searched for studies from inception to 12 November 2023. Diagnostic parameters, such as sensitivity, specificity, diagnostic odds ratio and area under the summary receiver-operating characteristic (SROC) curve (AUC), were calculated for the included studies. A systematic review and meta-analysis was performed. RESULTS: A total of 22 studies with 2461 patients were included in our study. The pooled sensitivity, specificity and diagnostic odds ratio of NGS were 87% (95% confidence interval [CI]: 83-90), 94% (95% CI: 91-96) and 111 (95% CI: 70-177), respectively. On the other hand, the pooled sensitivity, specificity and diagnostic odds ratio of culture were 63% (95% CI: 58-67), 98% (95% CI: 96-99) and 93 (95% CI: 40-212), respectively. The SROC curve for NGS and culture showed that the AUCs are 0.96 (95% CI: 0.94-0.98) and 0.82 (95% CI: 0.79-0.86), respectively. CONCLUSION: This systematic review and meta-analysis found NGS had higher sensitivity and diagnostic accuracy but slightly lower specificity than culture. Based on the pooled results, we suggested NGS may have the potential to be a new tool for the diagnosis of PJI. LEVEL OF EVIDENCE: Level IV.

3.
FASEB J ; 38(10): e23646, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38795328

RESUMO

Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-ß-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3ß/ß-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.


Assuntos
Autofagia Mediada por Chaperonas , Glicogênio Sintase Quinase 3 beta , Inflamação , Proteína 2 de Membrana Associada ao Lisossomo , Células-Tronco Mesenquimais , Osteogênese , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , beta Catenina , Animais , Osteogênese/fisiologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , beta Catenina/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Inflamação/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/genética , Transdução de Sinais , Masculino , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Diferenciação Celular , Osteoclastos/metabolismo
4.
Int J Biol Macromol ; 266(Pt 2): 131357, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580010

RESUMO

The microenvironment of bone defect site is vital for bone regeneration. Severe bone defect is often accompanied with severe inflammation and elevated generation of reactive oxygen species (ROS) during bone repair. In recent years, the unfriendly local microenvironment has been paid more and more attention. Some bioactive materials with the ability to regulate the microenvironment to promote bone regeneration urgently need to be developed. Here, we develop a multifunctional composite hydrogel composed of photo-responsive methacrylate silk fibroin (SFMA), laponite (LAP) nanocomposite and tannic acid (TA), aiming to endow hydrogel with antioxidant, anti-inflammatory and osteogenic induction ability. Characterization results confirmed that the SFMA-LAP@TA hydrogel could significantly improve the mechanical properties of hydrogel. The ROS-Scavenging ability of the hydrogel enabled bone marrow mesenchymal stem cells (BMSCs) to survive against H2O2-induced oxidative stress. In addition, the SFMA-LAP@TA hydrogel effectively decreased the expression of pro-inflammatory factors in RAW264.7. More importantly, the SFMA-LAP@TA hydrogel could enhance the expression of osteogenic markers of BMSCs under inflammatory condition and greatly promote new bone formation in a critical-sized cranial defect model. Above all, the multifunctional hydrogel could effectively promote bone regeneration in vitro and in vivo by scavenging ROS and reducing inflammation, providing a prospective strategy for bone regeneration.


Assuntos
Regeneração Óssea , Fibroínas , Hidrogéis , Inflamação , Células-Tronco Mesenquimais , Nanocompostos , Osteogênese , Polifenóis , Espécies Reativas de Oxigênio , Taninos , Regeneração Óssea/efeitos dos fármacos , Animais , Fibroínas/química , Fibroínas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Taninos/química , Taninos/farmacologia , Camundongos , Inflamação/tratamento farmacológico , Nanocompostos/química , Hidrogéis/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células RAW 264.7 , Osteogênese/efeitos dos fármacos , Metacrilatos/química , Metacrilatos/farmacologia , Ratos , Estresse Oxidativo/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
5.
Cell Tissue Res ; 396(2): 269-281, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38470494

RESUMO

Nonunion is a challenging complication of fractures for the surgeon. Recently the Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum protein retention receptor 2 (KDELR2) has been found that involved in osteogenesis imperfecta. However, the exact mechanism is still unclear. In this study, we used lentivirus infection and mouse fracture model to investigate the role of KDELR2 in osteogenesis. Our results showed that KDELR2 knockdown inhibited the osteogenic differentiation of mBMSCs, whereas KDELR2 overexpression had the opposite effect. Furthermore, the levels of active-ß-catenin and phospho-GSK3ß (Ser9) were upregulated by KDELR2 overexpression and downregulated by KDELR2 knockdown. In the fracture model, mBMSCs overexpressing KDELR2 promoted healing. In conclusion, KDELR2 promotes the osteogenesis of mBMSCs by regulating the GSK3ß/ß-catenin signaling pathway.


Assuntos
Diferenciação Celular , Glicogênio Sintase Quinase 3 beta , Células-Tronco Mesenquimais , Osteogênese , beta Catenina , Animais , Camundongos , beta Catenina/metabolismo , Células da Medula Óssea/metabolismo , Células da Medula Óssea/citologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Transdução de Sinais
6.
Biomater Sci ; 12(8): 2121-2135, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38456326

RESUMO

Natural polymer-based hydrogels have been widely applied in bone tissue engineering due to their excellent biocompatibility and outstanding ability of drug encapsulation. However, they have relatively weak mechanical properties and lack bioactivity. Hence, we developed a bioactive nanoparticle composite hydrogel by incorporating LAPONITE®, which is an osteo-inductive inorganic nanoparticle. The incorporation of the nanoparticle significantly enhanced its mechanical properties. In vitro evaluation indicated that the nanocomposite hydrogel could exhibit good biocompatibility. Besides, the nanocomposite hydrogel was proved to have excellent osteogenic ability with up-regulated expression of osteogenic markers such as type I collagen (COL-I), runt-related transcription factor-2 (Runx-2) and osteocalcin (OCN). Furthermore, the in vivo study confirmed that the composite nanocomposite hydrogel could significantly promote new bone formation, providing a prospective strategy for bone tissue regeneration.


Assuntos
Fibroínas , Nanopartículas , Hidrogéis , Nanogéis , Regeneração Óssea , Engenharia Tecidual , Seda
7.
J Shoulder Elbow Surg ; 33(4): 948-958, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38182024

RESUMO

BACKGROUND: Heterotopic ossification (HO) is a common complication after elbow fracture surgery and can lead to severe upper extremity disability. The radiographic localization of postoperative HO has been reported previously. However, there is no literature examining the distribution of postoperative HO at the three-dimensional (3D) level. This study aimed to investigate 1) the distribution characteristics of postoperative HO and 2) the possible risk factors affecting the severity of postoperative HO at a 3D level. METHODS: A retrospective review was conducted of patients who presented to our institution with HO secondary to elbow fracture between 13 January 2020 and 16 February 2023. Computed tomography scans of 56 elbows before elbow release surgery were reconstructed in 3D. HO was identified using density thresholds combined with manual identification and segmentation. The elbow joint and HO were divided into six regions according to three planes: the transepicondylar plane, the lateral ridge of the trochlear plane, and the radiocapitellar joint and coronoid facet plane. The differences in the volume of regional HO associated with different initial injuries were analyzed. RESULTS: Postoperative HO was predominantly present in the medial aspect of the capsule in 52 patients (93%), in the lateral aspect of the capsule in 45 patients (80%), in the medial supracondylar in 32 patients (57%), and in the lateral supracondylar, radial head, and ulnar region in the same number of 28 patients (50%). The median and interquartile range volume of total postoperative HO was 1683 (777-4894) mm3. The median and interquartile range volume of regional postoperative HO were: 584 (121-1454) mm3 at medial aspect of capsule, 207 (5-568) mm3 at lateral aspect of capsule, 25 (0-449) mm3 at medial supracondylar, 1 (0-288) at lateral supracondylar, 2 (0-478) at proximal radius and 7 (0-203) mm3 at the proximal ulna. In the subgroups with Injury Severity Score > or = 16, Gustilo-Anderson II, normal uric acid levels, elevated alkaline phosphatase, and body mass index > or = 24, the median HO volume exceeds that of the respective control groups. CONCLUSION: The medial aspect of the capsule was the area with the highest frequency and median volume of postoperative HO among all initial elbow injury types. Patients with higher Gustilo-Anderson grade, Injury Severity Score, alkaline phosphatase or Body Mass Index had higher median volume of postoperative HO.


Assuntos
Traumatismos do Braço , Fraturas do Cotovelo , Lesões no Cotovelo , Articulação do Cotovelo , Ossificação Heterotópica , Humanos , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/cirurgia , Cotovelo , Prevalência , Fosfatase Alcalina , Traumatismos do Braço/complicações , Estudos Retrospectivos , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/epidemiologia , Ossificação Heterotópica/etiologia , Amplitude de Movimento Articular , Resultado do Tratamento
8.
J Mol Med (Berl) ; 101(7): 783-799, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37162558

RESUMO

Chaperone-mediated autophagy (CMA) plays multiple roles in cell metabolism. We found that lysosome-associated membrane protein type 2A (LAMP2A), a crucial protein of CMA, plays a key role in the control of mesenchymal stem cell (MSC) adipo-osteogenesis. We identified a differentially expressed CMA gene (LAMP2) in GEO datasets (GSE4911 and GSE494). Further, we performed co-expression analyses to define the relationships between CMA components genes and other relevant genes including Col1a1, Runx2, Wnt3 and Gsk3ß. Mouse BMSCs (mMSCs) exhibiting Lamp2a gene knockdown (LA-KD) and overexpression (LA-OE) were created using an adenovirus system; then we investigated LAMP2A function in vitro by Western blot, Oil Red staining, ALP staining, ARS staining and Immunofluorescence analysis. Next, we used a modified mouse model of tibial fracture to investigate LAMP2A function in vivo. LAMP2A knockdown in mMSCs decreased the levels of osteogenic-specific proteins (COL1A1 and RUNX2) and increased those of the adipogenesis markers PPARγ and C/EBPα; LAMP2A overexpression had the opposite effects. The active-ß-catenin and phospho-GSK3ß (Ser9) levels were upregulated by LAMP2A overexpression and downregulated by LAMP2A knockdown. In the mouse model of tibial fracture, mMSC-overexpressing LAMP2A improved bone healing, as demonstrated by microcomputed tomography and histological analyses. In summary, LAMP2A positively regulates mMSC osteogenesis and suppresses adipo-osteogenesis, probably via Wnt/ß-catenin/GSK3ß signaling. LAMP2A promoted fracture-healing in the mouse model of tibial fracture. KEY MESSAGES: • LAMP2 positively regulates the mBMSCs osteogenic differentiation. • LAMP2 negatively regulates the mBMSCs adipogenic differentiation. • LAMP2 regulates mBMSCs osteogenesis via Wnt/ß-catenin/GSK3ß signaling pathway. • LAMP2 overexpression mBMSCs promote the fracture healing.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Camundongos , Animais , Osteogênese/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Microtomografia por Raio-X , Osteoblastos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular/fisiologia , Transdução de Sinais , Via de Sinalização Wnt , Células Cultivadas
9.
FASEB J ; 37(6): e22950, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37144883

RESUMO

Fracture nonunion and bone defects are challenging for orthopedic surgeons. Milk fat globule-epidermal growth factor 8 (MFG-E8), a glycoprotein possibly secreted by macrophages in a fracture hematoma, participates in bone development. However, the role of MFG-E8 in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. We investigated the osteogenic effect of MFG-E8 in vitro and in vivo. The CCK-8 assay was used to assess the effect of recombinant human MFG-E8 (rhMFG-E8) on the viability of hBMSCs. Osteogenesis was investigated using RT-PCR, Western blotting, and immunofluorescence. Alkaline phosphatase (ALP) and Alizarin red staining were used to evaluate ALP activity and mineralization, respectively. An enzyme-linked immunosorbent assay was conducted to evaluate the secretory MFG-E8 concentration. Knockdown and overexpression of MFG-E8 in hBMSCs were established via siRNA and lentivirus vector transfection, respectively. Exogenous rhMFG-E8 was used to verify the in vivo therapeutic effect in a tibia bone defect model based on radiographic analysis and histological evaluation. Endogenous and secretory MFG-E8 levels increased significantly during the early osteogenic differentiation of hBMSCs. Knockdown of MFG-E8 inhibited the osteogenic differentiation of hBMSCs. Overexpression of MFG-E8 and rhMFG-E8 protein increased the expression of osteogenesis-related genes and proteins and enhanced calcium deposition. The active ß-catenin to total ß-catenin ratio and the p-GSK3ß protein level were increased by MFG-E8. The MFG-E8-induced enhanced osteogenic differentiation of hBMSCs was partially attenuated by a GSK3ß/ß-catenin signaling inhibitor. Recombinant MFG-E8 accelerated bone healing in a rat tibial-defect model. In conclusion, MFG-E8 promotes the osteogenic differentiation of hBMSCs by regulating the GSK3ß/ß-catenin signaling pathway and so, is a potential therapeutic target.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Humanos , Ratos , Animais , Osteogênese/fisiologia , beta Catenina/genética , beta Catenina/metabolismo , Fator VIII/metabolismo , Fator VIII/farmacologia , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Transdução de Sinais/fisiologia , Diferenciação Celular/fisiologia , Glicoproteínas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células Cultivadas , Via de Sinalização Wnt , Células da Medula Óssea/metabolismo
10.
Stem Cell Rev Rep ; 19(4): 968-982, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36609902

RESUMO

BACKGROUND: Epidermal growth factor-like domain protein 7 (EGFL7) is a secreted protein that is differentially expressed in the bone microenvironment; however, the effect of EGFL7 on the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) is largely unknown. METHODS: EGFL7 expression in the fracture microenvironment was analyzed based on the Gene Expression Omnibus (GEO) database. Knockdown of EGFL7 by small interfering RNA (siRNA) and in vitro stimulation with recombinant human EGFL7 (rhEGFL7) protein were used to assess alterations in downstream signaling and changes in the osteogenic differentiation and proliferation of hBMSCs. A γ-secretase inhibitor was used to further explore whether inhibition of Notch signaling rescued the osteogenic-inhibitory effect of EGFL7 knockdown in hBMSCs. A femoral defect model was established to verify the effect of recombinant mouse EGFL7 on bone healing in vivo. RESULTS: EGFL7 expression increased during hBMSC osteogenesis. Knockdown of EGFL7 impaired hBMSC osteogenesis and activated Notch1/NICD/Hes1 signaling. rhEGFL7 promoted hBMSC osteogenesis and downregulated Notch1 signaling. The osteoblast-inhibitory effect of EGFL7 knockdown was rescued by Notch1 signaling inhibition. Recombinant EGFL7 led to enhanced bone healing in mice with femoral defects. CONCLUSIONS: EGFL7 promotes osteogenesis of hBMSCs partly via downregulation of Notch1 signaling.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Humanos , Camundongos , Animais , Osteogênese/genética , Regulação para Baixo/genética , Células Cultivadas , Transdução de Sinais , Diferenciação Celular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Osteoblastos/metabolismo , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo
11.
J Colloid Interface Sci ; 625: 512-520, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35749846

RESUMO

The organic-inorganic heterojunction composites possessed excellent physical and chemistry properties has enormous potential in the field of wastewater purification. Herein, the novel PI-BiPO4 heterojunction photocatalysts were synthesized via facile hydrothermal method. The different ratio PI-BiPO4 composites exhibited remarkable photodegradation performance than that of the pure BiPO4. The enhanced photocatalytic activity of 75PI-BiPO4 composites was ascribed to the improvement of light absorption ability and larger specific surface area. What is more, the forming of heterojunction between PI and BiPO4 was conduce to the separation and migration of the photogenerated electron-hole pairs. The h+ and O2- confirmed by EPR facility were predominant reactive species in the photocatalytic process. In addition, the feasible pathway of photocatalytic degradation TC were inferred on account of the UPLC-MS/MS results. This work provides a novel organic-inorganic heterojunction composites for supporting the field of the pollutant purification.


Assuntos
Bismuto , Poluentes Químicos da Água , Bismuto/química , Catálise , Cromatografia Líquida , Espectrometria de Massas em Tandem , Poluentes Químicos da Água/química
12.
Front Cell Dev Biol ; 10: 817877, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35198560

RESUMO

Mesenchymal stem cell (MSC) transplantation has been widely used as a potential treatment for a variety of diseases. However, the contradiction between the low survival rate of transplanted cells and the beneficial therapeutic effects has affected its clinical use. Lysosomes as organelles at the center of cellular recycling and metabolic signaling, play essential roles in MSC homeostasis. In the first part of this review, we summarize the role of lysosomal acidification dysfunction in MSC senescence. In the second part, we summarize some of the potential strategies targeting lysosomal proteins to enhance the therapeutic effect of MSCs.

13.
Environ Technol ; 43(23): 3580-3590, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33966616

RESUMO

Recently, the micro-nano bubble (MB) technology has attracted people's attention due to its special advantages. Here, we carried out the technology of combining MB and hydrogen peroxide (MB/H2O2) to achieve efficient degradation of tetracycline wastewater. The effect of MB/H2O2 technology on the degradation efficiency of tetracycline was deeply analysed by investigating the reaction time, H2O2 dosage, pH and MB inlet flow. The results showed that the degradation rate of tetracycline hydrochloride by MB/H2O2 technology can reach 92.43%, which is 9.44 and 3.94 times that of MB and H2O2 alone. Through electron spin resonance (ESR) analysis and free radical quenching experiments, a possible mechanism for MB/H2O2 technology to efficiently degrade TC was proposed. In the MB/H2O2 system, the high temperature and high pressure environment generated when MB ruptures can activate H2O2 to obtain a higher number of active oxygen species. •OH is the main reactive oxygen radical in the process of MB/H2O2 degradation of TC, followed by HO2•/•O2-. In addition, the possible intermediate products of the oxidation TC process were identified by HPLC-MS technology. Under the action of •OH and HO2•/•O2- free radicals, TC molecules undergo demethylation and hydroxylation, ring-opening reactions, isomerization, deethylation, deacylation, deamination and dehydration reactions to generate intermediate products and finally convert them into CO2 and H2O. The development of MB/H2O2 technology can potentially be used to efficiently remove TC substances in the water environment and provide a new method for water purification.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Antibacterianos , Radicais Livres , Humanos , Peróxido de Hidrogênio/química , Oxirredução , Tetraciclina , Águas Residuárias
14.
Stem Cell Res Ther ; 12(1): 525, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620242

RESUMO

BACKGROUND: Globally, bone fractures are the most common musculoskeletal trauma, and approximately 8-10% of cases that fall into the categories of delayed or non-union healing. To date, there are no efficient pharmacological agents to accelerate the healing of bone fractures. Thus, it is necessary to find new strategies that accelerate bone healing and reduce the incidence of non-union or delayed fracture healing. Previous studies have revealed that the plasminogen activation system has been demonstrated to play an important role in bone metabolism. However, the function of SERPINB2 in the osteogenesis of hBMSCs remains unclear. Therefore, in this study, we investigated the effects and mechanism of SERPINB2 on osteogenic differentiation. METHODS: We investigated the osteogenesis effects of hBMSCs by both exogenous SerpinB2 protein and SERPINB2 gene silencing in vitro. Cell proliferation assay was used to assess the effect of exogenous SerpinB2 or SERPINB2 silencing on proliferation of hBMSCs. qPCR and Western blotting analysis detected the expression of target genes and proteins respectively. ALP staining was used to evaluated ALP activity and Alizarin Red staining (ARS) was used to evaluate mineral deposition. In vivo, a murie tibial fracture model was established, histological evaluation and radiographic analysis was used to confirm the therapeutic effects of SERPINB2 silencing in fracture healing. Statistical significance between two groups was determined by Student's t test, one-way ANOVA or Bonferroni's post-hoc test according to the distribution of the tested population. RESULTS: The addition of exogenous SerpinB2 protein inhibted osteoblast differentiation of hBMSCs in vitro, while SERPINB2 gene silencing significant promote osteoblast differentiation of hBMSCs in vitro. And silenced SERPINB2 gene also increased mineral deposits. Moreover, ß-catenin levels were up-regulated by SERPINB2 gene depletion. And the enhancement of osteogenic differentiation induced by SERPINB2 silencing was almost inhibited by specific Wnt/ß-catenin signaling pathway inhibitor. In a murine tibial fracture model, local injection of SERPINB2 siRNA improved bone fracture healing. CONCLUSIONS: Taken together, these findings indicate that SERPINB2 silencing promoted osteogenic differentiation of BMSCs via the Wnt/ß-catenin signaling pathway, and silenced SERPINB2 in vivo effectively promotes fracture healing, suggesting that SERPINB2 may be a novel target for bone fracture healing.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Células-Tronco Mesenquimais , Osteogênese , Via de Sinalização Wnt , Animais , Células da Medula Óssea/metabolismo , Diferenciação Celular , Células Cultivadas , Fraturas Ósseas/terapia , Inativação Gênica , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteogênese/genética , beta Catenina/genética , beta Catenina/metabolismo
15.
Front Pharmacol ; 12: 607635, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935702

RESUMO

Glycyrrhizic acid (GA) is a major triterpene glycoside isolated from liquorice root that has been shown to inhibit osteoclastogenesis. However, there have been no reports regarding the effect of GA on osteogenic differentiation. Therefore, this study was performed to explore the effects and mechanism of action of GA on osteogenesis. A CCK-8 array was used to assess cell viability. The osteogenic capability was investigated by real-time quantitative PCR, western blotting and immunofluorescence analyses. ALP staining and ARS were used to evaluate ALP activity and mineralization, respectively. GA-GelMA hydrogels were designed to verify the therapeutic effects of GA in vivo by radiographic analysis and histological evaluation. Our results show that GA had no significant influence on the viability or proliferation of human bone marrow stromal cells (hBMSCs). GA promoted osteogenic differentiation and enhanced calcium deposition. Furthermore, ratio of active ß-catenin and total ß-catenin protein increased after treatment with GA. Wnt/catenin signaling inhibitor partially attenuated the effects of GA on osteogenic differentiation. In a mouse femoral fracture model, GA-GelMA hydrogels accelerated bone healing. Our results show that GA promotes the osteogenic differentiation of hBMSCs by modulating the Wnt/ß-catenin signaling pathway. GA-GelMA hydrogels promoted bone fracture healing. GA has potential as a cost-effective treatment of bone defects.

16.
Stem Cell Res Ther ; 12(1): 268, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947456

RESUMO

BACKGROUND: Inflammatory microenvironment is significant to the differentiation and function of mesenchymal stem cells (MSCs). It evidentially influences the osteoblastogenesis of MSCs. IL-34, a newly discovered cytokine, playing a key role in metabolism. However, the research on its functional role in the osteogenesis of MSCs was rarely reported. Here, we described the regulatory effects of low-dose IL-34 on both osteoblastogenesis and osteoclastogenesis. METHODS: We performed the osteogenic effects of hBMSCs by exogenous and overexpressed IL-34 in vitro, so were the osteoclastogenesis effects of mBMMs by extracellular IL-34. CCK-8 was used to assess the effect of IL-34 on the viability of hBMSCs and mBMMs. ALP, ARS, and TRAP staining was used to evaluate ALP activity, mineral deposition, and osteoclastogenesis, respectively. qRT-PCR and Western blotting analysis were performed to detect the expression of target genes and proteins. ELISA was used to evaluate the concentrations of IL-34. In vivo, a rat tibial osteotomy model and an OVX model were established. Radiographic analysis and histological evaluation were performed to confirm the therapeutic effects of IL-34 in fracture healing and osteoporosis. Statistical differences were evaluated by two-tailed Student's t test, one-way ANOVA with Bonferroni's post hoc test, and two-way ANOVA with Bonferroni multiple comparisons post hoc test in the comparison of 2 groups, more than 2 groups, and different time points of treated groups, respectively. RESULTS: Promoted osteoblastogenesis of hBMSCs was observed after treated by exogenous or overexpressed IL-34 in vitro, confirmed by increased mineral deposits and ALP activity. Furthermore, exogenous or overexpressed IL-34 enhanced the expression of p-AKT and p-ERK. The specific AKT and ERK signaling pathway inhibitors suppressed the enhancement of osteoblastogenesis induced by IL-34. In a rat tibial osteotomy model, imaging and histological analyses testified the local injection of exogenous IL-34 improved bone healing. However, the additional IL-34 has no influence on both osteoclastogenesis of mBMMs in vitro and osteoporosis of OVX model of rat in vivo. CONCLUSIONS: Collectively, our study demonstrate that low-dose IL-34 regulates osteogenesis of hBMSCs partly via the PIK/AKT and ERK signaling pathway and enhances fracture healing, with neither promoting nor preventing osteoclastogenesis in vitro and osteoporosis in vivo.


Assuntos
Osteogênese , Proteínas Proto-Oncogênicas c-akt , Animais , Diferenciação Celular , Células Cultivadas , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais
17.
Langmuir ; 37(16): 5049-5058, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33849275

RESUMO

The oxygen vacancy caused by ultrathin structures would be introduced into the semiconductor photocatalyst to boost its photocatalytic activity. Herein, ultrathin Bi2O3-Bi2WO6 nanosheet composites have been successfully synthesized via a facile hydrothermal method. Compared to pure Bi2WO6 nanosheets, the Bi2O3-Bi2WO6 nanosheet composites possess abundant oxygen vacancies, which was confirmed by the positron annihilation spectra. The ultrathin Bi2O3-Bi2WO6 nanosheet composites exhibited remarkable photocatalytic degradation performance for oxytetracycline compared with that of pure Bi2WO6 nanosheets. The excellent photocatalytic activities of Bi2O3-Bi2WO6 composites could be attributed to the heterojunction structure and the oxygen vacancies caused by ultrathin structures.

18.
Int Immunopharmacol ; 88: 106960, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32919219

RESUMO

BACKGROUND: The treatment of bone defects has always been a problem for clinicians. In recent years, research on human bone mesenchymal stem cells (hBMSCs) has found that promoting their osteogenic differentiation could be a useful therapeutic strategy for bone healing. Previous studies have been reported that Withania somnifera Dunal inhibits osteoclastogenesis by inhibiting the NF-κB signaling pathway. Withanolide B is an active component of W. somnifera Dunal, but its role in osteogenic differentiation of hBMSCs remains unknown. Here, we performed a preliminary study on the role of Withanolide B in promoting osteogenic differentiation and its possible mechanism. METHODS: We investigated the effect of Withanolide B on osteogenic differentiation of hBMSCs in vitro and in vivo. The effect of Withanolide B on the activity of hBMSCs was verified by CCK-8 assay and quantitative Real-time polymerase chain reaction (qPCR) and Western blotting analysis were used to verify the effect of Withanolide B on osteogenic differentiation-specific genes and proteins. The effect of Withanolide B on ALP activity and mineral deposition was verified by ALP and ARS staining. We then used a rat tibial osteotomy model to observe the effect of Withanolide B on bone healing. RESULTS: Withanolide B is noncytotoxic to hBMSCs and can effectively promote their osteogenic differentiation. Moreover, we found that Withanolide B can regulate the osteogenic differentiation of hBMSCs through the ERK1/2 and Wnt/ß-catenin signaling pathways. When inhibitors of the ERK1/2 and Wnt/ß-catenin signaling pathways were used, the enhancement of osteogenic differentiation induced by Withanolide B was attenuated. Withanolide B also effectively promoted bone healing in the rat tibial osteotomy model. CONCLUSIONS: Our results suggest that Withanolide B can promote the osteogenic differentiation of hBMSCs through the ERK1/2 and Wnt/ß-catenin signaling pathways and can effectively promote bone defect healing.


Assuntos
Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Vitanolídeos/farmacologia , Animais , Células da Medula Óssea/citologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Ratos Sprague-Dawley , Tíbia/efeitos dos fármacos , Tíbia/lesões , Via de Sinalização Wnt/efeitos dos fármacos
19.
J Shoulder Elbow Surg ; 29(5): 996-1001, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32305108

RESUMO

BACKGROUND: Heterotopic ossification (HO) is a common complication after surgery for elbow trauma. Uric acid is the end product of purine metabolism and has several physiological and pathogenic roles. However, the relationship between HO and uric acid has not been explored. This retrospective study aimed to assess the relationship between HO and serum uric acid (SUA). MATERIAL AND METHODS: We retrospectively reviewed data from 155 patients undergoing elbow trauma surgery in our hospital between January 2013 and December 2018. One hundred patients were included according to the inclusion criteria. They were divided into 2 groups according to the presence or absence of HO, and the SUA level was compared between groups using the independent samples t test. The optimal prognostic cutoff value was obtained using the maximum value of the Youden index. RESULTS: The SUA level was significantly higher in the HO group than in the non-HO group (362.0 ± 87.4 µmol/L vs. 318.3 ± 87.0 µmol/L; P < .05). Using the maximum value of Youden index, 317.5 µmol/L was determined to be the optimal SUA cutoff value for the prediction of HO, with a sensitivity of 68.75% (95% confidence interval [CI], 54.67%-80.05%) and specificity of 55.77% (95% CI, 42.34%-68.40%). CONCLUSIONS: Our study was the first to find that the high SUA level is a risk factor for HO of the elbow joint after trauma. Moreover, 317.5 µmol/L is the SUA threshold predicting the occurrence and development of HO of the elbow, with high sensitivity and specificity.


Assuntos
Articulação do Cotovelo/cirurgia , Cotovelo/cirurgia , Ossificação Heterotópica/sangue , Ossificação Heterotópica/etiologia , Ácido Úrico/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Prognóstico , Amplitude de Movimento Articular , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Fatores de Tempo , Adulto Jovem , Lesões no Cotovelo
20.
Small ; 16(5): e1904783, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31943792

RESUMO

The increasing application of exposed high energy facet is an effective strategy to improve the photocatalytic performance of photocatalysts because the vacancies are beneficial to photocatalytic reaction. Vacancy dominates numerous distinct properties of semiconductor materials and thus plays a conclusive role in the photocatalysis applications. In this work, two kinds of BiOI nanomaterials with different vacancies are synthesized via a facile solvothermal method. The positron annihilation analysis shows that the thinner BiOI nanosheets possess larger-sized vacancy than BiOI nanoplates. Thus, BiOI nanosheets show the enhanced separation efficiency of electron-hole pairs and adsorption ability for contaminants under visible light. The results are also validated with the first-principle computation. Therefore, higher photocatalytic activity to the photodegradation of tetracycline is observed from the nanosheets than that obtained from BiOI nanoplates. This work not only arouses attention to vacancies, but also opens up an avenue for precision design of vacancies to prepare novel photocatalytic materials driven under solar light.

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