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1.
Open Forum Infect Dis ; 8(8): ofab384, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34386546

RESUMO

Background: As the coronavirus pandemic spreads, more and more people are infected with severe acute respiratory syndrome coronavirus 2. The short- and medium-term effects of the infection have been described, but the description of the long-term sequelae is lacking in the literature. Methods: Patients healed from coronavirus disease 2019 (COVID-19) from February 2020 to May 2020 were considered for inclusion in this study, regardless of the severity of the disease during the acute phase. Eligible patients were consecutively contacted and a semistructured interview was administered between February and March 2021 by trained medical staff. Results: Three hundred three patients were eligible and accepted to participate in the study and were enrolled. Of those surveyed, most patients (81%) reported at least 1 symptom, and the most prevalent symptoms were fatigue (52%), pain (48%), and sleep disorders (47%). Sensory alterations were present in 28% of surveyed patients, but in most of these cases (74% of those affected by sensory alterations or 20% of the overall sample) symptoms reported were either anosmia or dysgeusia. Higher prevalence was generally observed with increasing age, although the most relevant differences were observed when comparing young versus middle-aged adults. Conclusions: At 12 months after acute infection, COVID-19 survivors were still suffering from symptoms identified at shorter follow-up, and the most frequent symptoms included fatigue, pain, and sleep disorders. A more severe impairment in the acute phase did not seem to predict more severe complications.

2.
Children (Basel) ; 8(8)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34438536

RESUMO

BACKGROUND: The rapid diffusion of Coronavirus disease (COVID-19) in Northern Italy led the Italian government to dictate a national lockdown from 12 March 2020 to 5 May 2020. The aim of this observational cohort study is to analyze the differences in the number of pediatric patients' admission to the Emergency Room (ER) and in the type and causes of injury. METHODS: The pediatric population during the pandemic was compared to a similar group of patients admitted to the ER in 2019. Sex, age, triage color-code at admission, cause of trauma and presence of symptoms related to COVID-19 infection, discharge diagnosis and discharge modes were investigated. RESULTS: The lockdown period led to a reduction of 87.0% in ER admissions with a particular decrease in patients older than 12 years old. Moreover, a trend towards more severe codes and an increase in home-related injuries were observed during the pandemic, whereas the diagnosis of fracture was less frequent in the pre-pandemic group (p < 0.0001). CONCLUSIONS: A significant decrease in the ER attendances was reported during the lockdown. A shift in the cause and type of injury was observed; only the most serious traumas sought medical care with a higher percentage of severe triage codes and fractures.

3.
J Clin Med ; 10(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208115

RESUMO

BACKGROUND: SARS-CoV-2 pandemic is one of the biggest challenges for many health systems in the world, making lots of them overwhelmed by the enormous pressure to manage patients. We reported our Institutional Experience, with specific aims to describe the distribution and type of treated injuries, and the organizational setup of our hospital. METHODS: Data of fractured patients admitted for surgical treatment in the time frames 9 March 2020-4 May 2020 and 1 March 2019-31 May 2019 were collected and compared. Furthermore, surgery duration and some parameters of effectiveness in health management were compared. RESULTS: A total of 498 patients were included. Mean age significantly lower age in 2019 and femoral fractures were significantly more frequent 2020. Mean surgery time was significantly longer in 2020. Mortality rate difference between the two years was found to be statistically significant. Time interval between diagnosis and surgery and between diagnosis and discharge/decease was significantly lower in 2020. In 2020, no patient admitted with a negative swab turned positive in any of the following tests for SARS-CoV-2. CONCLUSIONS: The COVID-19 pandemic has modified the epidemiology of hospitalized patients for traumatic reasons, leading to an increased admission of older patients with femoral fractures. Nevertheless, our institutional experience showed that an efficient change in the hospital organization, with an improvement of several parameters of effectiveness in health management, led to a null infection rate between patients.

4.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199089

RESUMO

The meniscus possesses low self-healing properties. A perfect regenerative technique for this tissue has not yet been developed. This work aims to evaluate the role of hypoxia in meniscal development in vitro. Menisci from neonatal pigs (day 0) were harvested and cultured under two different atmospheric conditions: hypoxia (1% O2) and normoxia (21% O2) for up to 14 days. Samples were analysed at 0, 7 and 14 days by histochemical (Safranin-O staining), immunofluorescence and RT-PCR (in both methods for SOX-9, HIF-1α, collagen I and II), and biochemical (DNA, GAGs, DNA/GAGs ratio) techniques to record any possible differences in the maturation of meniscal cells. Safranin-O staining showed increments in matrix deposition and round-shape "fibro-chondrocytic" cells in hypoxia-cultured menisci compared with controls under normal atmospheric conditions. The same maturation shifting was observed by immunofluorescence and RT-PCR analysis: SOX-9 and collagen II increased from day zero up to 14 days under a hypoxic environment. An increment of DNA/GAGs ratio typical of mature meniscal tissue (characterized by fewer cells and more GAGs) was observed by biochemical analysis. This study shows that hypoxia can be considered as a booster to achieve meniscal cell maturation, and opens new opportunities in the field of meniscus tissue engineering.


Assuntos
Diferenciação Celular , Hipóxia/metabolismo , Menisco/citologia , Menisco/metabolismo , Animais , Biomarcadores , Células Cultivadas , Condrócitos/metabolismo , Expressão Gênica , Glicosaminoglicanos/metabolismo , Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Suínos , Engenharia Tecidual/métodos
5.
Turk Neurosurg ; 31(4): 484-492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33978225

RESUMO

AIM: To describe the history of the anterior approach to the lumbar spine from the beginning to the minimal invasive techniques that the authors have developed, and to discuss its advantages and drawbacks. MATERIAL AND METHODS: The authors collected published data on the evolution of the anterior approach in the lumbar spine, and described its potential in different pathologies focusing on minimally invasive techniques. RESULTS: Several successful techniques of anterior lumbar approach have been developed over the years, leading to a progressive less invasive anatomical exposure of the spine. Anterior approaches of the lumbar spine gained popularity as an alternative to posterior routes in the management of tumors, infections, traumas, degenerative or deformity diseases and as a salvage procedure after posterior surgery. CONCLUSION: Advantages of the retroperitoneal anterior approach of the lumbar spine are well accepted: it preserves the anatomical structures of the abdomen and posterior tension band, avoiding muscle dissection. The implantation of lordotic cages with larger footprint improves local lordosis and fusion rate even in revision surgery. Drawbacks of traditional retroperitoneal approaches may be: vascular injury, deep venous thrombosis, risk of retrograde ejaculation in male in case of L5-S1 dissection. Therefore, several minimal invasive techniques have been developed to decrease the risks related to the traditional approaches. However, a long learning curve is required to achieve good skills and to manage possible technical concerns and complications.


Assuntos
Procedimentos Neurocirúrgicos/tendências , Fusão Vertebral , Coluna Vertebral/cirurgia , Feminino , Humanos , Lordose/cirurgia , Vértebras Lombares/cirurgia , Região Lombossacral/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Espaço Retroperitoneal/cirurgia , Fusão Vertebral/métodos , Fusão Vertebral/tendências , Lesões do Sistema Vascular/etiologia
6.
Acta Orthop ; 92(3): 274-279, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33410360

RESUMO

Background and purpose - Several surgical approaches are used in primary total hip arthroplasty (THA). In this randomized controlled trial we compared gait, risk of fall, self-reported and clinical measurements between subjects after direct superior approach (DSA) versus posterolateral approach (PL) for THA.Patients and methods - Participants with DSA (n = 22; age 74 [SD 8.9]) and PL (n = 23; age 72 [7.7]) underwent gait analysis, risk of fall assessment and Timed Up and Go Test (TUG) before (PRE), 1 month (T1) and 3 months after (T3) surgery. Data on bleeding and surgical time was collected.Results - DSA resulted in longer surgical times (90 [14] vs. 77 [20] min) but lower blood loss (149 [66] vs. 225 [125] mL) than PL. DSA had lower risk of fall at T3 compared with T1 and higher TUG scores at T3 compared with T1 and PRE. PL improved balance at T3 compared with T1 and PRE. Spatiotemporal gait parameters improved over time for both DSA and PL with no inter-group differences, whereas DSA, regarding hip rotation range of motion, showed lower values at T3 and T1 compared with PRE and, furthermore, this group had lower values at T1 and T3 compared with PL. All foregoing comparisons are statistically signficant (p < 0.05)Interpretation - DSA showed longer surgical time and lower blood loss compared with PL and early improvements in TUG, spatiotemporal, and kinematic gait parameters, highlighting rapid muscle strength recovery.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Artroplastia de Quadril/métodos , Marcha/fisiologia , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Quadril/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Osteoartrite do Quadril/complicações , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Autorrelato , Fatores de Tempo , Resultado do Tratamento
7.
Br Med Bull ; 137(1): 51-69, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33517365

RESUMO

BACKGROUND: This article systematically summarizes the present evidences, published in the last 20 years, regarding the pre- and post-operative factors, which may influence recovery of the function of the quadriceps muscle group following total knee arthroplasty (TKA). We following the PRISMA methodology, including meta-analyses and high-level evidence studies (prospective trials, and, when unavailable, retrospective studies). SOURCES OF DATA: Pubmed and Cochrane databases: 582 articles were identified and 54 of them were selected. AREAS OF AGREEMENT: Tourniquets inflated at high pressure exert a detrimental effect on the quadriceps muscle group. Faster quadriceps recovery takes place using mini-invasive approaches, an eight-week rehabilitation period including balance training and the use of nutraceuticals. AREAS OF DISAGREEMENT: Pre-habilitation and pre-operative factors, analgesic methods and different TKA implants. GROWING POINTS AND AREAS TIMELY FOR DEVELOPING RESEARCH: Telerehabilitation seems a cost-effective tool for rehabilitation after TKA. Patients' optimization protocols before TKA should include standardized nutraceuticals intake.

8.
Front Med (Lausanne) ; 7: 566770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178713

RESUMO

Proximal femoral fractures in older adults are not uncommon and represent a great challenge for orthopedic surgeons because of the high risks of complications. In the COVID-19 panorama, fractures occurring in infected older adults become an even more intricate task because of concomitant metabolic derangements due to SARS-CoV-2. Multidisciplinary protocols are mandatory and pharmacological treatment in infected patients should be tailored. Regrettably, the spread of the virus in northern Italy, has been faster than scientific progress in characterizing the disease and many hospitals have had to manage the symptoms on a daily clinical bases. Our Italian hospital in the region of Lombardy, which has been the epicenter of the Italian pandemic, has admitted sixteen patients with fractured femurs in March and April 2020. The first seven patients were treated with the antithrombotic prophylaxis of a single daily dose of low-molecular-weight heparin, but we observed the highest prevalence of deaths from cardiovascular complications (four deaths). By doubling the daily dose of anticoagulants in the subsequent patients, we observed a reduction in the incidence of death (one death out of nine). Controversies exist about the surgical treatment of fractures in older adults during this pandemic. However, we have observed an increased survival after fall trauma in infected older adults if treated with high doses of anticoagulant. Although not being statistically significant, our results are in line with the current knowledge of the pathophysiology of SARS-CoV-2 infection, but more studies should be shared about the efficacy and dosage of anticoagulants in traumatic injuries of the elderly.

9.
Br Med Bull ; 135(1): 50-61, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-32776138

RESUMO

BACKGROUND: Low levels of vitamin D are common in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), but it is still unclear whether the outcome of such surgery is related to vitamin D levels. SOURCES OF DATA: Publicly available electronic databases were systematically reviewed to update knowledge about the role of vitamin D in THA and TKA patients, and to appraise the correlation between vitamin D levels before surgery and post-surgical outcomes. Eight studies were included in our review: six employed prospective observational designs, two reported retrospective database interrogations. Six prospective observational studies and two retrospective database interrogations matched inclusion and exclusion criteria. AREAS OF AGREEMENT: Patients undergoing THA and TKA have a high prevalence of hypovitaminosis D. Five of eight studies (62.5%) report a statistically significant association between low vitamin D status and worse outcomes after THA and TKA. AREAS OF CONTROVERSY: Different explanations have been proposed for vitamin D insufficiency, but some authors have questioned the correctness of the methods used to measure the vitamin D levels. GROWING POINTS: A trial focusing on the role of vitamin D supplementation on safety and outcomes of patients undergoing THA and TKA with low vitamin D status is ongoing. AREAS TIMELY FOR DEVELOPING RESEARCH: Further studies should explore the possible causal relationship between vitamin D status and outcomes of THA and TKA and verify the laboratory methods to analyse it.

12.
Comput Biol Med ; 121: 103775, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32568670

RESUMO

BACKGROUND: Clinical registries are powerful tools for collecting uniform data longitudinally, thus making it possible to evaluate the outcome of patients affected by a specific pathology. In the context of total joint arthroplasty, registries serve also as post-market surveillance. Adoption of registries is a heavy burden for clinical settings in terms of resources and infrastructures. Excessive workload leads to incomplete data collection which undermines the effectiveness of a registry and consequently the workload needs to be optimised. METHODS: Starting from the use case of the Istituto Ortopedico Galeazzi, the time and personnel dedicated to the registry was estimated. Analysis of the data collected in the first years enabled us to propose a methodology for workload reduction. Different Machine Learning models were leveraged to predict patients with excellent satisfaction to reduce the number of assessments in their clinical post-operative follow-up. Moreover, feature selection was used to identify any unnecessary clinical scale to collect. RESULTS: Given an acceptance rate of 3500 patients per year, 22 doctors and 6 non-medical employees were required to adopt a registry properly. Among the tested models, the Naïve Bayes gave the best performance (AUPRC = 0.81) in predicting patient satisfaction at six months. Moreover, we found that the 12-item Short Form was poorly informative in predicting satisfaction at six-months. CONCLUSIONS: In this study machine learning was leveraged to provide a methodology to reduce workload in the use of pathology registries. Such workload reduction can have a considerable impact at a larger scale, and improve registry feasibility in high-volume hospitals.


Assuntos
Artroplastia de Substituição , Hospitais com Alto Volume de Atendimentos , Teorema de Bayes , Estudos de Viabilidade , Humanos , Sistema de Registros
13.
Clin Pharmacol Ther ; 108(4): 719-729, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32438454

RESUMO

The pandemic spread of the new coronavirus disease 2019 (COVID-19) infection in China first, and all over the world at present, has become a global health emergency due to the rapidly increasing number of affected patients. Currently, a clear relationship between COVID-19 infection incidence and/or complications due to chronic or occasional treatments for other pathologies is still not clear, albeit the COVID-19 pandemic may condition the treatment strategy of complex disorders, such as osteoarthritis (OA). Importantly, OA is the most common age-related joint disease, affecting more than 80% of people older than the age of 55, an age burden also shared with the highest severity in COVID-19 patients. OA patients often show a large array of concomitant pathologies, such as diabetes, inflammation, and cardiovascular diseases that are again shared with COVID-19 patients and may therefore increase complications. Moreover, different OA treatments, such as NSAIDs, paracetamol, corticosteroids, opioids, or other molecules have a wide array of iatrogenic effects, potentially increasing COVID-19 secondary infection incidence or complications. In this review we critically analyze the evidence on either negative or positive effects of drugs commonly used to manage OA in this particular scenario. This would provide orthopedic surgeons in particular, and physicians, pharmacologists, and clinicians in general, a comprehensive description about the safety of the current pharmacological approaches and a decision-making tool to treat their OA patients as the coronavirus pandemic continues.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Gerenciamento Clínico , Osteoartrite/tratamento farmacológico , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , COVID-19 , Infecções por Coronavirus/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Osteoartrite/epidemiologia , Pneumonia Viral/epidemiologia , SARS-CoV-2
14.
Cells ; 9(3)2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204578

RESUMO

Bone is an active tissue where bone mineralization and resorption occur simultaneously. In the case of fracture, there are numerous factors required to facilitate bone healing including precursor cells and blood vessels. To evaluate the interaction between bone marrow-derived mesenchymal stem cells (BMSC)-the precursor cells able to differentiate into bone-forming cells and human umbilical vein endothelial cells (HUVEC)-a cell source widely used for the study of blood vessels. We performed direct coculture of BMSC and HUVEC in normoxia and chemically induced hypoxia using Cobalt(II) chloride and Dimethyloxaloylglycine and in the condition where oxygen level was maintained at 1% as well. Cell proliferation was analyzed by crystal violet staining. Osteogenesis was examined by Alizarin Red and Collagen type I staining. Expression of angiogenic factor-vascular endothelial growth factor (VEGF) and endothelial marker-von Willebrand factor (VWF) were demonstrated by immunohistochemistry and enzyme-linked immunosorbent assay. The quantitative polymerase chain reaction was also used to evaluate gene expression. The results showed that coculture in normoxia could retain both osteogenic differentiation and endothelial markers while hypoxic condition limits cell proliferation and osteogenesis but favors the angiogenic function even after 1 of day treatment.


Assuntos
Diferenciação Celular , Células Endoteliais da Veia Umbilical Humana/citologia , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica , Osteogênese , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Hipóxia Celular , Proliferação de Células , Técnicas de Cocultura , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Fator de von Willebrand/metabolismo
15.
Cells ; 9(2)2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31973209

RESUMO

Joint motion and postnatal stress of weight bearing are the principal factors that determine the phenotypical and architectural changes that characterize the maturation process of the meniscus. In this study, the effect of compressive forces on the meniscus will be evaluated in a litter of 12 Dobermann Pinschers, of approximately 2 months of age, euthanized as affected by the quadriceps contracture muscle syndrome of a single limb focusing on extracellular matrix remodeling and cell-extracellular matrix interaction (i.e., meniscal cells maturation, collagen fibers typology and arrangement). The affected limbs were considered as models of continuous compression while the physiologic loaded limbs were considered as controls. The results of this study suggest that a compressive continuous force, applied to the native meniscal cells, triggers an early maturation of the cellular phenotype, at the expense of the proper organization of collagen fibers. Nevertheless, an application of a compressive force could be useful in the engineering process of meniscal tissue in order to induce a faster achievement of the mature cellular phenotype and, consequently, the earlier production of the fundamental extracellular matrix (ECM), in order to improve cellular viability and adhesion of the cells within a hypothetical synthetic scaffold.


Assuntos
Força Compressiva/fisiologia , Matriz Extracelular/fisiologia , Menisco/fisiologia , Animais , Fenômenos Biomecânicos , DNA/metabolismo , Cães , Módulo de Elasticidade , Glicosaminoglicanos/metabolismo , Imageamento por Ressonância Magnética , Menisco/diagnóstico por imagem
16.
Vet Sci ; 6(4)2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31717551

RESUMO

Osteochondral defects are a common problem in both human medicine and veterinary practice although with important limits concerning the cartilaginous tissue regeneration. Interest in the subchondral bone has grown, as it is now considered a key element in the osteochondral defect healing. The aim of this work was to generate and to evaluate the architecture of three cell-free scaffolds made of collagen, magnesium/hydroxyapatite and collagen hydroxyapatite/wollastonite to be implanted in a sheep animal model. Scaffolds were designed in a bilayer configuration and a novel "Honey" configuration, where columns of hydroxyapatite were inserted within the collagen matrix. The use of different types of scaffolds allowed us to identify the best scaffold in terms of integration and tissue regeneration. The animals included were divided into four groups: three were treated using different types of scaffold while one was left untreated and represented the control group. Evaluations were made at 3 months through CT analysis. The novel "Honey" configuration of the scaffold with hydroxyapatite seems to allow for a better reparative process, although we are still far from obtaining a complete restoration of the defect at this time point of follow-up.

17.
Stem Cells Int ; 2019: 9178436, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191688

RESUMO

Total hip arthroplasty (THA) represents one of the commonest surgical procedures in the orthopedic field. Osteointegration of the implant with native bone is essential for an optimal result; thus, the quality of the patient's bone surrounding the implant (i.e., the bone stock) is crucial. However, in some cases, the bone stock is insufficient and needs to be improved with autologous grafts rich in multipotent cells (i.e., from the iliac crest, from the head of the femur, or from the subchondral bone harvested from the acetabulum) or allogenic frozen bone. It is not known if the harvesting site may influence the osteogenic potential of these cells. Thus, our aim was to characterize and compare multipotent cells collected from the bone marrow, acetabular subchondral bone, and trabecular bone on the femoral head with a focus on osteogenic differentiation. The cells from three sources had a fibroblast-like phenotype and expressed surface antigens CD73, CD90, and CD105 and are negative to CD11b, CD34, and CD45. Although all these cells could be induced to differentiate into osteoblasts, chondrocytes, and adipocytes, they displayed different differentiation potentials. In osteogenic differentiation condition, the cells from the acetabulum had the lowest accumulation of calcium deposit while the cells originated from the bone marrow and femur created a considerably increased amount of the deposit. These findings were confirmed by quantitative polymerase chain reaction (qPCR). In chondrogenic and adipogenic conditions, bone marrow cells possessed a predominant differential capacity compared with the others, illustrated by high collagen type II expression together with a cartilage-like lacuna structure and the presence of fat-specific markers, respectively. To our knowledge, this is the first study comparing and demonstrating that the progenitor cells obtained from diverse surgical sites in hip replacement procedure share common characteristics of MSC but differ about plasticity and may provide rational for clinical application in cell therapy and bone grafting. The project number L1033 is registered with ClinicalTrials.gov NCT03369457.

19.
Dev Cell ; 49(5): 748-763.e7, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31105007

RESUMO

Oxygen (O2) is both an indispensable metabolic substrate and a regulatory signal that controls the activity of Hypoxia-Inducible Factor 1α (Hif1a), a mediator of the cellular adaptation to low O2 tension (hypoxia). Hypoxic cells require Hif1a to survive. Additionally, Hif1a is an inhibitor of mitochondrial respiration. Hence, we hypothesized that enhancing mitochondrial respiration is detrimental to the survival of hypoxic cells in vivo. We tested this hypothesis in the fetal growth plate, which is hypoxic. Our findings show that mitochondrial respiration is dispensable for survival of growth plate chondrocytes. Furthermore, its impairment prevents the extreme hypoxia and the massive chondrocyte death observed in growth plates lacking Hif1a. Consequently, augmenting mitochondrial respiration affects the survival of hypoxic chondrocytes by, at least in part, increasing intracellular hypoxia. We thus propose that partial suppression of mitochondrial respiration is crucial during development to protect the tissues that are physiologically hypoxic from lethal intracellular anoxia.


Assuntos
Condrócitos/fisiologia , Desenvolvimento Fetal/fisiologia , Lâmina de Crescimento/fisiologia , Hipóxia/fisiopatologia , Mitocôndrias/fisiologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Respiração Celular , Sobrevivência Celular , Condrócitos/citologia , Proteínas de Ligação a DNA/fisiologia , Feminino , Proteínas de Grupo de Alta Mobilidade/fisiologia , Proteínas de Homeodomínio/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
20.
Bone Res ; 7: 7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30792937

RESUMO

Osteoblasts, which are the bone-forming cells, operate in a hypoxic environment. The transcription factors hypoxia-inducible factor-1α (HIF1) and HIF2 are key mediators of the cellular response to hypoxia. Both are expressed in osteoblasts. HIF1 is known to be a positive regulator of bone formation. Conversely, the role of HIF2 in the control osteoblast biology is still poorly understood. In this study, we used mouse genetics to demonstrate that HIF2 is an inhibitor of osteoblastogenesis and bone mass accrual. Moreover, we provided evidence that HIF2 impairs osteoblast differentiation at least in part, by upregulating the transcription factor Sox9. Our findings constitute a paradigm shift, as activation of the hypoxia-signaling pathway has traditionally been associated with increased bone formation through HIF1. Inhibiting HIF2 could thus represent a therapeutic approach for the treatment of the low bone mass observed in chronic diseases, osteoporosis, or aging.

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