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Diabetic calcific tendinopathy is the leading cause of chronic pain, mobility restriction, and tendon rupture in patients with diabetes. Tendon stem/progenitor cells (TSPCs) have been implicated in the development of diabetic calcified tendinopathy, but the molecular mechanisms remain unclear. This study found that diabetic tendons have a hyperoxic environment, characterized by increased oxygen delivery channels and carriers. In hyperoxic environment, TSPCs showed enhanced osteogenic differentiation and increased levels of reactive oxygen species (ROS). Additionally, hypoxia-inducible factor-1a (HIF-1a), a protein involved in regulating cellular responses to hyperoxia, was decreased in TSPCs by the ubiquitin-proteasome system. By intervening with antioxidant N-acetyl-L-cysteine (NAC) and overexpressing HIF-1a, we discovered that blocking the ROS/HIF-1a signalling axis significantly inhibited the osteogenic differentiation ability of TSPCs. Animal experiments further confirmed that hyperoxic environment could cause calcification in the Achilles tendon tissue of rats, while NAC intervention prevented calcification. These findings demonstrate that hyperoxia in diabetic tendons promotes osteogenic differentiation of TSPCs through the ROS/HIF-1a signalling axis. This study provides a new theoretical basis and research target for preventing and treating diabetic calcified tendinopathy.
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Diferenciação Celular , Diabetes Mellitus Experimental , Subunidade alfa do Fator 1 Induzível por Hipóxia , Osteogênese , Espécies Reativas de Oxigênio , Transdução de Sinais , Células-Tronco , Tendões , Animais , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Espécies Reativas de Oxigênio/metabolismo , Células-Tronco/metabolismo , Células-Tronco/citologia , Ratos , Tendões/metabolismo , Tendões/patologia , Masculino , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Ratos Sprague-Dawley , Hiperóxia/metabolismo , Acetilcisteína/farmacologiaRESUMO
BACKGROUND: Elderly patients with femoral neck fracture have high perioperative blood loss according to the trauma and hip arthroplasty surgery. Tranexamic acid is a fibrinolytic inhibitor and has been widely used in hip fracture patients to against perioperative anemia. The aim of the present meta-analysis was to evaluate the efficacy and safety of Tranexamic acid (TXA) in elderly patients with femoral neck fracture undergoing hip arthroplasty. METHODS: We performed search using Pubmed, EMBASE, Cochrane Reviews, and Web of Science databases to identify all relevant research studies published from inception to June 2022. Randomized controlled studies and high-quality cohort studies that reported the perioperative use of TXA in patients with femoral neck fractures treated with arthroplasty, and made a comparison with the control group were included. Meta-analysis was performed using Review Manager 5.3 to assess the efficacy and safety of TXA. Subgroup analysis was conducted to further investigate the impact caused by surgery types and administration routes on the efficacy and safety outcomes. RESULTS: Five randomized controlled trials (RCTs) and eight cohort studies published from January 2015 to June 2022 were included in this meta-analysis. The results showed significant reductions in the rate of allogeneic blood transfusion, total blood loss (TBL) and postoperative hemoglobin (Hb) drop in the TXA group compared with the control group, while no significant difference was found in the intraoperative blood loss, postoperative drainage, hospital length of stay (LOS), re-admission rate, and wound complications between the two groups. The incidence of thromboembolic events and mortality showed no significant difference. Subgroup analysis indicated that surgery types and administration routes did not change the overall tendency. CONCLUSION: The current evidence shows that both intravascular administration (IV) and topical administration of TXA can significantly decrease the perioperative transfusion rate and TBL without increasing the risk of thromboembolic complications in elderly patients with femoral neck fracture.
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Antifibrinolíticos , Artroplastia de Quadril , Perda Sanguínea Cirúrgica , Fraturas do Colo Femoral , Ácido Tranexâmico , Idoso , Humanos , Antifibrinolíticos/toxicidade , Artroplastia de Quadril/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Fraturas do Colo Femoral/cirurgia , Ácido Tranexâmico/uso terapêuticoRESUMO
PURPOSE: To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures. METHODS: A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18-65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center. Exclusion criteria were serious life-threatening diseases, open fractures, fractures delayed for more than 3 weeks, fracture sites ≥2, etc. Then patients were divided into dislocation and no-dislocation groups. Patient demographics, injury characteristics, surgery-related outcomes, and postoperative functional outcomes were collected and analyzed. The functional outcomes of SER ankle fractures were assessed postoperatively at 1-year face-to-face follow-up using the foot and ankle outcome score (FAOS) and American orthopedic foot and ankle society score and by 2 experienced orthopedic physicians. Relevant data were analyzed using SPSS version 22.0 by Chi-square or t-test. RESULTS: During the study period, there were 371 ankle fractures. Among them, 190 (51.2%) were SER patterns with 69 (36.3%) combined with dislocations. Compared with the no-dislocation group, the dislocation group showed no statistically significant differences in gender, age composition, fracture type, preoperative complications with diabetes, smoking history, preoperative waiting time, operation time, and length of hospital stay (all p > 0.05), but a significantly higher Lauge-Hansen injury grade (p < 0.001) and syndesmotic screw fixation rate (p = 0.033). Moreover, the functional recovery was poorer, revealing a significantly lower FAOS in the sport/rec scale (p < 0.001). Subgroup analysis showed that among SER IV ankle fracture patients, FAOS was much lower in pain (p = 0.042) and sport/rec scales (p < 0.001) for those with dislocations. American orthopedic foot and ankle society score revealed no significant difference between dislocation and no-dislocation patients. CONCLUSION: Dislocation in SER ankle fractures suggests more severe injury and negatively affects functional recovery, mainly manifested as more pain and poorer motor function, especially in SER IV ankle cases.
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Tendinopathy describes a complex pathology of the tendon characterized by abnormalities in the microstructure, composition, and cellularity of the tendon, leading to pain, limitation of activity and reduced function. Nevertheless, the mechanism of tendinopathy has not been fully elucidated, and the treatment of tendinopathy remains a challenge. High mobility group box 1 (HMGB1), a highly conserved and multifaceted nuclear protein, exerts multiple roles and high functional variability and is involved in many biological and pathological processes. In recent years, several studies have suggested that HMGB1 is associated with tendinopathy and may play a key role in the pathogenesis of tendinopathy. Therefore, this review summarizes the expression and distribution of HMGB1 in tendinopathy, focuses on the roles of HMGB1 and HMGB1-based potential mechanisms involved in tendinopathy, and finally summarizes the findings on HMGB1-based therapeutic approaches in tendinopathy, probably providing new insight into the mechanism and further potential therapeutic targets of tendinopathy.
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Proteína HMGB1 , Tendinopatia , Humanos , Proteína HMGB1/metabolismo , Tendões/metabolismo , Tendinopatia/terapia , Tendinopatia/patologiaRESUMO
Osteoporosis (OP) is a systemic disease characterized by decreased bone mass and degeneration of bone microstructure. In recent years, more and more researches have focused on the close relationship between gut microbiota (GM) and the occurrence and progression of OP, and the regulation of probiotics and prebiotics on bone metabolism has gradually become a research hotspot. Based on the influence of brain-gut-bone axis on bone metabolism, this review expounds the potential mechanisms of probiotics and prebiotics on OP from next perspectives: regulation of intestinal metabolites, regulation of intestinal epithelial barrier function, involvement of neuromodulation, involvement of immune regulation and involvement of endocrine regulation, so as to provide a novel and promising idea for the prevention and treatment of OP in the future.
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Osteoporose , Probióticos , Humanos , Prebióticos , Probióticos/uso terapêutico , Intestinos , Encéfalo/metabolismo , Osteoporose/prevenção & controleRESUMO
Osteoporosis (OP) is the most prevalent metabolic bone disease, characterized by the low bone mass and microarchitectural deterioration of bone tissue. Glucocorticoid (GC) clinically acts as one of the anti-inflammatory, immune-modulating, and therapeutic drugs, whereas the long-term use of GC may cause rapid bone resorption, followed by prolonged and profound suppression of bone formation, resulting in the GC-induced OP (GIOP). GIOP ranks the first among secondary OP and is a pivotal risk for fracture, as well as high disability rate and mortality, at both societal and personal levels, vital costs. Gut microbiota (GM), known as the "second gene pool" of human body, is highly correlated with maintaining the bone mass and bone quality, and the relation between GM and bone metabolism has gradually become a research hotspot. Herein, combined with recent studies and based on the cross-linking relationship between GM and OP, this review is aimed to discuss the potential mechanisms of GM and its metabolites on the OP, as well as the moderating effects of GC on GM, thereby providing an emerging thought for prevention and treatment of GIOP.
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Conservadores da Densidade Óssea , Microbioma Gastrointestinal , Osteoporose , Humanos , Glucocorticoides/farmacologia , Osteoporose/tratamento farmacológico , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêuticoRESUMO
BACKGROUND: Surgery is the preferred treatment option for the elderly patients with hip fractures. However, the choice of general anesthesia (GA) or regional anesthesia (RA) remains controversial. The quality of evidence has further improved with the advent of several high-quality randomized clinical trials (RCTs) in the last two years. The purpose of this study was to compare the clinical outcomes of two anesthetic techniques in elderly patients undergoing hip fracture surgeries. METHODS: Eligible studies were identified from PubMed/MEDLINE, Web of Science, Scopus, EMBASE and reference lists from January 2000 to June 2022 in this current systematic review and meta-analysis. The outcomes included the surgery-related outcomes (duration of surgery, duration of anesthesia, intraoperative blood loss and number of transfusions) and postoperative outcomes (30-day mortality, postoperative delirium,cardiovascular events and other complications). RESULTS: A total of 10 RCTs were included, and a total of 3594 patients were analyzed. RA was associated with shorter duration of surgery, shorter length of hospital stays and less intraoperative blood loss compared to GA. There were no significant differences between the two groups in the number of blood transfusions, duration of anesthesia, 30-day mortality or postoperative delirium. CONCLUSIONS: Our pooled analysis identified no significant differences in terms of the safety between RA and GA, while RA reduces intraoperative blood loss, length of hospital stays and duration of surgery. These results suggest that RA appears to be preferable for the elderly patients with hip fractures.
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Anestesia por Condução , Delírio do Despertar , Fraturas do Quadril , Humanos , Idoso , Perda Sanguínea Cirúrgica/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Anestesia Geral , Fraturas do Quadril/cirurgiaRESUMO
PURPOSE: Ankle fracture-dislocations are among the most severe injuries, and the use of an external fixator as a recommended fixation method has some disadvantages. The aim of this study was to compare the clinical outcomes and complication rates of external and K-wire fixations in the treatment of ankle fracture dislocations. METHODS: A total of 67 patients with ankle fracture-dislocations requiring temporary external or percutaneous K-wire fixation were included. The exclusion criteria were pilon fractures, open fractures, and those who required acute open reduction internal fixation (ORIF). The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, a 10-point visual analog scale (VAS) score (range 0-10), and complications before and after the definitive surgery were recorded. RESULTS: A significant difference between the two groups was not observed for age, sex, affected side, fracture type, smoking status, or diabetes. The average AOFAS scores were 83.2 and 83.3, the median VAS scores were 3 and 3, and the complication rates were 32.4% and 6.7% in the external and K-wire fixation groups, respectively (p = 0.010). However, skin necrosis, re-dislocation of the ankle, surgical wound infection, and posttraumatic ankle osteoarthritis frequency were not significantly different between the groups, except for pin-sites infection (p = 0.036). CONCLUSION: Ankle fracture-dislocations using percutaneous k-wire fixation showed a low rate of complications and favorable clinical outcomes. This method could be a good alternative treatment option for ankle fracture-dislocations.
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Fraturas do Tornozelo , Fratura-Luxação , Humanos , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Fraturas do Tornozelo/etiologia , Tornozelo , Resultado do Tratamento , Fixação de Fratura/efeitos adversos , Fixação de Fratura/métodos , Fixadores Externos/efeitos adversos , Fratura-Luxação/diagnóstico por imagem , Fratura-Luxação/cirurgia , Fratura-Luxação/etiologia , Fixação Interna de Fraturas/efeitos adversos , Estudos RetrospectivosRESUMO
Currently, the data for effect of sleep on falls-associated fractures in elderly individuals are still limited. This current study was aimed to assess the link between self-reported sleep characteristics and falls-associated fractures in elderly individuals. This study included a total of 20,497 participants from National Health and Nutritional Examination Survey (NHANES) 2005-2008, and 6,174 participants aged 45 years and older were identified. Self-reported sleep characteristics and conditions of falls-associated fractures of individuals were obtained via the method of personal questionnaires. In a total of 610 participants with exact history of fractures, 168 individuals with falls-associated fractures were identified, and the prevalence was 27.5%. The mean age of falls-associated fractures group was (72.1 ± 8.8) years, and the female (P < 0.001) occupied a higher proportion. Factors of living alone (P = 0.003), combined with hypertension (P = 0.003) and osteoporosis (P < 0.001), sleeping less or more (P = 0.009), and frequent snoring (P = 0.007) were linked to falls-associated fractures. Compared with sleep duration of 6 to 8 h/night, sleep duration of ≤4 h/night (odds ratio [OR] 1.858, 95% confidence interval [CI] 1.115-3.094) and of ≥9 h/night (OR 1.932, 95% CI 1.195-3.123) were related to an increased risk of falls-associated fractures. Collectively, our nationwide data noted that sleep characteristics were closely related to falls-associated fractures in elderly individuals, and a longer sleep duration may exhibit a protective effect against the falls-associated fractures, but it should be limited within 9 h/night.
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Acidentes por Quedas , Fraturas Ósseas , Duração do Sono , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Acidentes por Quedas/estatística & dados numéricos , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Inquéritos Nutricionais/estatística & dados numéricos , Fatores de Risco , Autorrelato/estatística & dados numéricos , Sono , Inquéritos Epidemiológicos , Fatores de TempoRESUMO
Osteoporosis (OP) is a systemic bone disease characterized by the decreased bone mass and destruction of bone microstructure, which tends to result in the enhanced bone fragility and related fractures, as well as high disability rate and mortality. Exercise is one of the most common, reliable and cost-effective interventions for the prevention and treatment of OP currently, and numerous studies have revealed the close association between gut microbiota (GM) and bone metabolism recently. Moreover, exercise can alter the structure, composition and abundance of GM, and further influence the body health via GM and its metabolites, and the changes of GM also depend on the choice of exercise modes. Herein, combined with relevant studies and based on the inseparable relationship between exercise intervention-GM-OP, this review is aimed to discuss the moderating effects and potential mechanisms of exercise intervention on GM and bone metabolism, as well as the interaction between them.
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Microbioma Gastrointestinal , Osteoporose , Humanos , Osteoporose/terapia , Osso e Ossos , Exercício Físico , Terapia por ExercícioRESUMO
Osteoporosis is a systemic metabolic bone disease characterized by the descending bone mass and destruction of bone microstructure, which tends to result in the increased bone fragility and associated fractures, as well as high disability rate and mortality. The relation between gut microbiota and bone metabolism has gradually become a research hotspot, and it has been verified that gut microbiota is closely associated with reduction of bone mass and incidence of osteoporosis recently. As a novel "organ transplantation" technique, fecal microbiota transplantation (FMT) mainly refers to the transplantation of gut microbiota from healthy donors to recipients with gut microbiota imbalance, so that the gut microbiota in recipients can be reshaped and play a normal function, and further prevent or treat the diseases related to gut microbiota disorder. Herein, based on the gut-bone axis and proven regulatory effects of gut microbiota on osteoporosis, this review expounds relevant basic researches and clinical practice of FMT on osteoporosis, thus demonstrating the potentials of FMT as a therapeutic option for osteoporosis and further providing certain reference for the future researches.
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Microbioma Gastrointestinal , Osteoporose , Humanos , Transplante de Microbiota Fecal/métodos , Osteoporose/terapiaRESUMO
BACKGROUND: With the increasing evidence provided by recent high-quality studies, the intravenous iron appears to be a reliable therapy for blood administration in geriatric patients with hip fractures. Here, this systematic review and meta-analysis were aimed to assess the effectiveness and safety of intravenous iron in geriatric patients sustaining hip fractures. METHODS: Potential pertinent literatures evaluating the effects of intravenous iron in the geriatric patients undergoing hip fractures were identified from Web of Science, PubMed, Embase, and Scopus. We performed a pairwise meta-analysis using fixed- and random-effects models, and the pooling of data was carried out by using RevMan 5.1. RESULTS: Four randomized controlled trials and four observational studies conform to inclusion criteria. The results of meta-analysis showed that intravenous iron reduced transfusion rates compared to the control group, yet the result did not reach statistical significance. The intravenous iron was related to lower transfusion volumes, shorter length of stay, and a reduced risk of nosocomial infections. And there was no significant difference in terms of the mortality and other complications between the treatment group and the control group. CONCLUSION: Current evidence suggests that intravenous iron reduces the transfusion volume, length of hospital stay, and risk of nosocomial infections. It takes about 7 days for intravenous iron to elevate hemoglobin by 1 g/dl and about 1 month for 2 g/dl. The safety profile of intravenous iron is also reassuring, and additional high-quality studies are needed.
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Infecção Hospitalar , Fraturas do Quadril , Administração Intravenosa , Idoso , Hemoglobinas , Fraturas do Quadril/cirurgia , Humanos , Ferro/uso terapêuticoRESUMO
Supination external rotation (SER) type ankle fracture is the most common ankle fracture in the Lauge-Hansen classification and is often accompanied with syndesmotic injury. However, the mechanism of this injury is indistinct and a suggestive role can be given by preoperative imaging. This study was to preoperatively predict whether SER type ankle fractures are accompanied with syndesmotic injuries by the means of lateral malleolus fracture mapping. One hundred and forty-eight patients diagnosed with SER type ankle fractures were retrospectively enrolled in this study. The baseline data were collected and computed tomography data were reconstructed in 3-dimensional (3D) model. Patients were divided into stable and unstable groups according to intraoperative Cotton test and whether the inferior tibiofibular screw was placed. All fracture lines were superimposed on the ankle template to create a fracture map, and the data on the fracture map were further measured. Logistic regression was conducted to identify relevant factors and the cutoff values were given using receiver operating characteristic curves. Forty-one patients were enrolled in the unstable group and 107 patients were enrolled in the stable group. The lateral malleolus fracture lines of the unstable group were higher and steeper than that in the stable group on lateral and posterior views. The fracture height of the posterior cortex and peak height were the significant contributing factors, and the cut-off values of posterior cortex, peak height and inclination angle were 40.35 mm (sensitivity: 78%, specificity: 82%), 55.34 mm (sensitivity: 85%, specificity: 70%) and 55.6° (sensitivity: 66%, specificity: 86%), respectively. In general, when the fracture lines of the lateral malleolus were high and steep, it was usually indicative of a syndesmotic injury and can be predicted by the preoperative 3D reconstruction of fracture height of posterior cortex, peak height and inclination angle. If the cut-off values of these indicators are exceeded, the syndesmotic injuries may be presented and need to be verified in the intraoperative Cotton test to decide whether to insert an inferior tibiofibular screw.
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BACKGROUND: We compared the effectiveness of the extensile lateral approach (ELA) and modified sinus tarsi approach (MSTA) with a variable-angle locking anterolateral plate in treating Sanders type II and III calcaneal fractures. METHODS: We reviewed 45 DIACFs treated by a single surgeon from 2017 to 2020. Open reduction using ELA and MSTA was performed in 25 and 20 patients, respectively. Follow-up evaluations included radiological assessments and clinical evaluations. RESULTS: Pre- and postoperative radiologic parameters for the calcaneus were significantly different. The average American Orthopaedic Foot and Ankle Society scores were 81.24 and 85.00, the mean visual analogue scale scores were 2.28 and 1.65, and the wound-related complication rates were 64.0% and 15.0% in the ELA and MSTA groups, respectively. Bony union was achieved in all cases. CONCLUSIONS: For Sanders type II and III fractures, MSTA seems to be a safer and more satisfactory method, with fewer postoperative complications.
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Traumatismos do Tornozelo , Calcâneo , Traumatismos do Pé , Fraturas Ósseas , Fraturas Intra-Articulares , Placas Ósseas , Calcâneo/diagnóstico por imagem , Calcâneo/cirurgia , Traumatismos do Pé/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Calcanhar , Humanos , Fraturas Intra-Articulares/diagnóstico por imagem , Fraturas Intra-Articulares/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The inhibition of sclerostin by the systemic administration of a monoclonal antibody (Scl-Ab) significantly increased bone mass and strength in fractured bones in animal models and non-fractured bones in ovariectomised (OVX) rats. In this study, the effects of Scl-Ab on healing were examined in a closed fracture model in OVX rats. Sixty Sprague-Dawley rats underwent an ovariectomy or a sham operation at 4 months of age, and a closed fracture of the right femur was performed 3 months later. Subcutaneous injections with Scl-Ab (25 mg/kg) or saline were then administered on day 1 after the fracture and twice a week for 8 weeks (n = 20 per group), at which time the fractured femurs were harvested for micro-computed tomography analysis, four-point bending mechanical testing and histomorphometric analysis to examine bone mass, bone strength and dynamic bone formation at the fracture site. The angiogenesis at the fracture site was also examined. Bone marrow stem cells were also isolated from the fractured bone to perform a colony-forming unit (CFU) assay and an alkaline phosphatase-positive (ALP(+)) CFU assay. OVX rats treated with Scl-Ab for 8 weeks had significantly increased bone mineral density and relative bone volume compared with OVX rats treated with saline. Similarly, maximum loading, energy to maximum load and stiffness in Scl-Ab-treated OVX rats were significantly higher than those in saline controls. The mineral apposition rate (MAR), mineralising surface (MS/BS) and bone formation rate (BFR/BS) were also significantly increased in Scl-Ab-treated group compared with the saline-treated group in OVX rats. Furthermore, the Scl-Ab-treated group had more CFUs and ALP(+) CFUs than the saline-treated group in OVX rats. No significant difference in angiogenesis at the fracture site was found between the groups. Our study demonstrated that Scl-Ab helped to increase bone mass, bone strength and bone formation at the fracture site in a closed femoral fracture model in OVX rats. Bone marrow stem cells in OVX rats injected with Scl-Ab also had increased CFUs and ALP(+) CFUs.
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Anticorpos/química , Proteínas Morfogenéticas Ósseas/química , Fraturas do Fêmur/imunologia , Fosfatase Alcalina/metabolismo , Animais , Peso Corporal , Células da Medula Óssea/citologia , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Consolidação da Fratura , Marcadores Genéticos , Injeções Subcutâneas , Neovascularização Patológica , Osteogênese , Ovariectomia , Ratos , Ratos Sprague-Dawley , Células-Tronco/citologia , Estresse Mecânico , Microtomografia por Raio-XRESUMO
Mesenchymal stem cells (MSCs) are a promising cell resource for tissue engineering. Sry-related high-mobility group box 11 (Sox11) plays critical roles in neural development and organogenesis. In the present study, we investigated the role of Sox11 in regulating trilineage differentiation (osteogenesis, adipogenesis, and chondrogenesis) and migration of MSCs, and explored the effect of systemically administrated Sox11-modified MSCs on bone fracture healing using the rat model of open femur fracture. Our results demonstrated that Sox11 overexpression increased the trilineage differentiation and migration of MSCs, as well as cell viability under oxidative stress. The effect of Sox11 on osteogenesis was confirmed by ectopic bone formation assay conducted in nude mice. In addition, we found that Sox11 could activate the bone morphogenetic protein (BMP)/Smad signaling pathway in MSCs. By dual-luciferase reporter assay, we also demonstrated that Sox11 could transcriptionally activate runt-related transcription factor 2 (Runx2) and CXC chemokine receptor-4 (CXCR4) expression. The activation of the BMP/Smad signaling pathway and Runx2, CXCR4 expression may have a synergic effect, which largely contributed to the effect of Sox11 on MSC fate determination and migration. Finally, using an open femur fracture model in rats, we found that a larger number of MSCs stably expressing Sox11 migrated to the fracture site and improved bone fracture healing. Taken together, our study shows that Sox11 is an important regulator of MSC differentiation and migration, and Sox11-modified MSCs may have clinical implication for accelerating bone fracture healing, which can reduce the delayed unions or nonunions.
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Consolidação da Fratura/fisiologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Fatores de Transcrição SOXC/fisiologia , Adipogenia/fisiologia , Animais , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular , Movimento Celular , Sobrevivência Celular , Condrogênese/fisiologia , Fraturas do Fêmur/patologia , Fraturas do Fêmur/terapia , Consolidação da Fratura/genética , Transplante de Células-Tronco Mesenquimais , Camundongos , Camundongos Nus , Osteogênese/fisiologia , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Fatores de Transcrição SOXC/genética , Transdução de Sinais , Proteínas Smad/genética , Proteínas Smad/metabolismoRESUMO
As a connective tissue, tendon connects the muscle and bone, and plays the key role in the locomotor system. Some previous studies have shown the pathological alternations in diabetic tendons, which might result in the structural and functional changes, and even accelerate the process of diabetic foot. In this review, we examined the current findings of the diabetic tendons in the form of various aspects, and summarized the clinical presentation, imaging, biomechanical, histopathological, cellular and molecular abnormalities in the diabetic tendons. The progress of diabetic tendon damage is complicated and the main hypotheses include the excessive accumulation of AGEs, the altered inflammatory response, neovascularization and insensitive neuropathy. However, the cellular and molecular mechanisms of these alterations are still ambiguous. Tendon stem/progenitor cells (TSPCs) have been discovered to play important roles in both tendon physiology and tendon pathology. Recently, we identified TSPCs from patellar tendons in our well-established diabetic rat model and found impaired tenogenic differentiation potential of these cells. We proposed a new hypothesis that the impaired cell functions of diabetic TSPCs might be the underlying cellular and molecular mechanism of the diabetic tendon alternations. These findings should be helpful to establish a better therapeutic strategy for diabetic tendon repair and regeneration.
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Diabetes Mellitus/patologia , Diabetes Mellitus/fisiopatologia , Tendões/patologia , Tendões/fisiopatologia , Animais , Fenômenos Biomecânicos , Diferenciação Celular , Humanos , Articulações/fisiopatologia , Masculino , Amplitude de Movimento Articular , Ratos , Regeneração , Células-Tronco/citologia , Tendões/citologiaRESUMO
PURPOSE: The aim of the study was to investigate the curative effects of transplantation of bone marrow mesenchymal stem cells (BMSCs) on intervertebral disc regeneration and to investigate the feasibility of the quantitative T2 mapping method for evaluating repair of the nucleus pulposus after implantation of BMSCs. METHODS: Forty-eight New Zealand white rabbits were used to establish the lumber disc degenerative model by stabbing the annulus fibrosus and then randomly divided into four groups, i.e. two weeks afterwards, BMSCs or phosphate-buffered saline (PBS) were transplanted into degenerative discs (BMSCs group and PBS group), while the operated rabbits without implantation of BMSCs or PBS served as the sham group and the rabbits without operation were used as the control group. At weeks two, six and ten after operation, the T2 values and disc height indices (DHI) were calculated by magnetic resonance imaging (MRI 3.0 T), and the gene expressions of type II collagen (COL2) and aggrecan (ACAN) in degenerative discs were evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR). T2 values for the nucleus pulposus were correlated with ACAN or COL2 expression by regression analysis. RESULTS: Cell clusters, disorganised fibres, interlamellar glycosaminoglycan (GAG) matrix and vascularisation were observed in lumber degenerative discs. BMSCs could be found to survive in intervertebral discs and differentiate into nucleus pulposus-like cells expressing COL2 and ACAN. The gene expression of COL2 and ACAN increased during ten weeks after transplantation as well as the T2 signal intensity and T2 value. The DHI in the BMSCs group decreased more slowly than that in PBS and sham groups. The T2 value correlated significantly with the gene expression of ACAN and COL2 in the nucleus pulposus. CONCLUSIONS: Transplantation of BMSCs was able to promote the regeneration of degenerative discs. Quantitative and non-invasive T2 mapping could be used to evaluate the regeneration of the nucleus pulposus with good sensitivity.
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Transplante de Medula Óssea/métodos , Degeneração do Disco Intervertebral/cirurgia , Disco Intervertebral/patologia , Imageamento por Ressonância Magnética/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Agrecanas/metabolismo , Animais , Colágeno Tipo II/metabolismo , Modelos Animais de Doenças , Estudos de Viabilidade , Disco Intervertebral/metabolismo , Disco Intervertebral/cirurgia , Coelhos , Reação em Cadeia da Polimerase em Tempo Real , RegeneraçãoRESUMO
Considering difficulties of achieving vertical incidence of beam in different positions of skin, it is significant to study potential effects of incidence angles of laser on incisions. Surgical platform with a 1064 nm continuous fiber laser was established. Incident angle was adopted and real-time temperature fluctuations in laser operating area could be monitored. The rats were treated with laser at day 0 and day 3 after incision modeling, and H&E, Masson, Sirius Red, and Immuno-histochemical staining and enzyme-linked immunosorbent assay were adopted at day 3, 7, 14 to analyze the performance of healing. Laser with energy density of 67.54 J/mm2 can effectively accelerate wound healing in vivo, in which a laser with incident angle around 60° can effectively avoid scar hyperplasia. Therefore, the use of low energy laser with a small deflection angle has a good clinical application prospect in promoting wound healing.
Assuntos
Terapia a Laser , Pele , Ratos , Animais , Incidência , Cicatrização , LasersRESUMO
To investigate the influence of laser parameters on the performance of tendon tissue, experiments were conducted and the process of laser-assisted tendon welding was studied. Several conclusions were drawn by analyzing the effects of laser parameters on the tensile strength, microstructure, and collagen content of tendon tissue incisions. The optimal parameters for laser welding tendon tissue were found to be a laser power of 5 W, a scanning speed of 150 mm/s, and a defocus amount of 0 mm, resulting in a laser energy density of 32.164 J/cm2 . At these parameters, the percentage of inactivated cells due to thermal damage was only 23.78%, and the tensile strength of the tendon tissue incisions reached 0.61 MPa. Additionally, the collagen content around the incision was measured to be 33.679%, composed of type I and type III collagens, with the latter accounting for 50.714% of the total collagen content.