Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 135
Filtrar
1.
Glia ; 72(9): 1674-1692, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38899731

RESUMO

Spinal cord injury (SCI) can result in severe motor and sensory deficits, for which currently no effective cure exists. The pathological process underlying this injury is extremely complex and involves many cell types in the central nervous system. In this study, we have uncovered a novel function for macrophage G protein-coupled receptor kinase-interactor 1 (GIT1) in promoting remyelination and functional repair after SCI. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we identified that GIT1 deficiency in macrophages led to an increased generation of tumor necrosis factor-alpha (TNFα), reduced proportion of mature oligodendrocytes (mOLs), impaired remyelination, and compromised functional recovery in vivo. These effects in GIT1 CKO mice were reversed with the administration of soluble TNF inhibitor. Moreover, bone marrow transplantation from GIT1 CWT mice reversed adverse outcomes in GIT1 CKO mice, further indicating the role of macrophage GIT1 in modulating spinal cord injury repair. Our in vitro experiments showed that macrophage GIT1 plays a critical role in secreting TNFα and influences the differentiation of oligodendrocyte precursor cells (OPCs) after stimulation with myelin debris. Collectively, our data uncovered a new role of macrophage GIT1 in regulating the transformation of OPCs into mOLs, essential for functional remyelination after SCI, suggesting that macrophage GIT1 could be a promising treatment target of SCI.


Assuntos
Diferenciação Celular , Macrófagos , Células Precursoras de Oligodendrócitos , Remielinização , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Macrófagos/metabolismo , Remielinização/fisiologia , Diferenciação Celular/fisiologia , Células Precursoras de Oligodendrócitos/metabolismo , Camundongos , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Recuperação de Função Fisiológica/fisiologia , Modelos Animais de Doenças , Fator de Necrose Tumoral alfa/metabolismo , Camundongos Transgênicos , Feminino , Proteínas Ativadoras de GTPase/metabolismo , Proteínas Ativadoras de GTPase/genética , Oligodendroglia/metabolismo
2.
Mol Med ; 30(1): 27, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378457

RESUMO

BACKGROUND: Isoorientin (ISO) is a glycosylated flavonoid with antitumor, anti-inflammatory, and antioxidant properties. However, its effects on bone metabolism remain largely unknown. METHODS: In this study, we aimed to investigate the effects of ISO on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in vitro and bone loss in post-ovariectomy (OVX) rats, as well as to elucidate the underlying mechanism. First, network pharmacology analysis indicated that MAPK1 and AKT1 may be potential therapeutic targets of ISO and that ISO has potential regulatory effects on the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways, as well as oxidative stress. ISO was added to RAW264.7 cells stimulated by RANKL, and its effects on osteoclast differentiation were evaluated using tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity measurement, and F-actin ring analysis. Reactive oxygen species (ROS) production in osteoclasts was detected using a ROS assay kit. The effects of ISO on RANKL-triggered molecular cascade response were further investigated by Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining. In addition, the therapeutic effects of ISO were evaluated in vivo. RESULTS: ISO inhibited osteoclastogenesis in a time- and concentration-dependent manner. Mechanistically, ISO downregulated the expression of the main transcription factor for osteoclast differentiation by inhibiting MAPK and PI3K/AKT1 signaling pathways. Moreover, ISO exhibited protective effects in OVX-induced bone loss rats. This was consistent with the results derived from network pharmacology. CONCLUSION: Our findings suggest a potential therapeutic utility of ISO in the management of osteoclast-associated bone diseases, including osteoporosis.


Assuntos
Reabsorção Óssea , Luteolina , Osteoporose , Feminino , Ratos , Animais , Reabsorção Óssea/patologia , Espécies Reativas de Oxigênio/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases , Farmacologia em Rede , Diferenciação Celular , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Osteoporose/tratamento farmacológico , Fatores de Transcrição NFATC/metabolismo
3.
Cytokine ; 164: 156134, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36804257

RESUMO

Disrupted osteoblastogenesis or aberrant activation of osteoclastogenesis usually results in the break of bone homeostasis thus causing bone-associated diseases like osteoporosis. Obacunone, as a natural compound present in citrus fruits, has been demonstrated for various biological activities including anti-cancer and anti-inflammatory properties. However, the role of obacunone in regulating osteoclastogenesis has not been elucidated so far. Here, using in vitro cell models of RANKL (Receptor activator of nuclear factor-kB ligand) and M-CSF (Macrophage-colony-stimulating factor)-induced osteoclastogenesis, we showed that obacunone inhibited osteoclast differentiation in RAW264.7 cells and bone marrow macrophages (BMMs), as evidenced by obacunone dose-dependent reduction in numbers of osteoclasts and downregulated expressions of osteoclastogenesis-associated key genes. The anti-osteoclastic properties of obacunone were associated with downregulated expressions of Integrin α1 and attenuated activation of Focal adhesion kinase (FAK) and Steroid receptor coactivator (Src) signaling. Functional Integrin α1 blockade or FAK-Src inhibition suppressed RANKL/M-CSF-induced osteoclastogenesis, while Integrin α1 overexpression or FAK/Src activation partially attenuated obacunone's effects on suppressing RANKL/M-CSF-induced osteoclast differentiation. Furthermore, in vivo administration of obacunone displayed super therapeutic effects in attenuating ovariectomy-induced bone loss in mice, as indicated by decreases in serum biomarkers of bone turnover, restoring of femur fracture maximum force, and reversing of the worsened bone-related parameters in ovariectomized animals. Taken together, these findings demonstrate that obacunone has pharmacological activities to suppress osteoclast differentiation through modulating the Integrin-FAK-Src pathway, and suggest that obacunone is a therapeutic candidate for the treatment and prevention of bone diseases such as osteoporosis.


Assuntos
Reabsorção Óssea , Osteoporose , Receptores de Esteroides , Feminino , Camundongos , Animais , Osteogênese , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Fator Estimulador de Colônias de Macrófagos/farmacologia , Fator Estimulador de Colônias de Macrófagos/metabolismo , Integrina alfa1/metabolismo , Diferenciação Celular , Osteoclastos/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Receptores de Esteroides/metabolismo , Ligante RANK/metabolismo
4.
Int Orthop ; 47(7): 1797-1804, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37074374

RESUMO

PURPOSE: Residual back pain (RBP) after percutaneous vertebral augmentation (PVA) still exists considerable, and it even affects daily life due to moderate or severe back pain. A variety of risk factors have been previously identified for developing residual back pain. However, there are conflicting reports regarding the association between sarcopenia and residual back pain. As such, the aim of this study was to investigate whether paraspinal muscle fatty degeneration is a predictor of residual back pain. METHODS: We retrospectively reviewed the medical records of patients with single-segment OVCF who underwent PVA from January 2016 to January 2022. Patients were divided into RBP group (86 patients) and control group (790 patients) according to whether the visual analog scale (VAS) score ≥ 4. The clinical and radiological data were analyzed. Paraspinal musculature fatty degeneration was measured using the Goutallier classification system (GCS) at the L4 - 5 intervertebral disc level. Univariate and multivariate logistic regression analyses were performed to identify risk factors. RESULTS: The results of multivariate logistical regression analysis revealed that posterior fascia injury (odds ratio (OR) = 5.23; 95% confidence interval (CI) 3.12-5.50; P < 0.001), as regards paraspinal muscle fatty degeneration, including Goutallier grading (OR = 12.23; 95% CI 7.81-23.41; P < 0.001), fCSA (OR = 3.06; 95% CI 1.63-6.84; P = 0.002), fCSA/CSA (%) (OR = 14.38; 95% CI 8.80-26.29; P < 0.001), and facet joint violation (OR = 8.54; 95% CI 6.35-15.71; P < 0.001) were identified as independent risk factors for RBP. CONCLUSIONS: Posterior fascia injury, paraspinal muscle fatty degeneration, and facet joint violation were identified as independent risk factors for RBP, with paraspinal muscle fatty degeneration playing an important role.


Assuntos
Degeneração do Disco Intervertebral , Humanos , Degeneração do Disco Intervertebral/epidemiologia , Degeneração do Disco Intervertebral/cirurgia , Estudos Retrospectivos , Músculos Paraespinais/diagnóstico por imagem , Dor nas Costas , Vértebras Lombares/cirurgia , Fatores de Risco , Imageamento por Ressonância Magnética
5.
Pain Med ; 23(2): 263-268, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34320640

RESUMO

OBJECTIVE: This study investigated the relationship between pain location and fracture type in patients with acute osteoporotic vertebral fracture (OVF). DESIGN: A prospective observational study. SUBJECT: A total of 306 patients with acute OVF were included. METHODS: The site of pain of each patient was recorded, and the patients were divided into a group with pain at the fracture site (group 1) and a group with pain at a non-fracture site (group 2). Fractures were classified into four types: type I, upper endplate type; type II, central type; type III, lower endplate type; and type IV, burst type. RESULTS: There were 146 patients in group 1, of whom 20.55% (30/146) had type I fractures, 33.56% (49/146) had type II fractures, 15.75% (23/146) had type III fractures, and 30.14% (44/146) had type IV fractures. There were 227 patients in group 2, of whom 57.27% (130/227) had type I fractures, 5.29% (12/227) had type II fractures, 35.24% (80/227) had type III fractures, and 2.20% (5/227) had type IV fractures. There was a statistical difference in the fracture type distribution between the two groups (P < 0.05). The visual analog scale score in group 1 was higher than that in group 2 at the initial diagnosis (P < 0.05). CONCLUSIONS: For patients with acute OVF, the site of pain is related to the type of fracture. The pain at the fracture site is more often observed in the central type and burst type of fractures, whereas pain at a non-fracture site is more often observed in the upper and lower endplate types of fractures. Additionally, when OVF is suspected, radiological assessment of the thoracic and lumbar spine is recommended to better detect fractures that could cause pain distal to the site of the fracture.


Assuntos
Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Fraturas por Osteoporose/complicações , Fraturas por Osteoporose/diagnóstico por imagem , Dor , Estudos Prospectivos , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem
6.
BMC Surg ; 22(1): 189, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568832

RESUMO

BACKGROUND: This study aimed to analyze the risk factors for proximal junctional kyphosis (PJK) for patients with chronic symptomatic osteoporotic thoracolumbar fractures (CSOTLF) and kyphosis who underwent long-segment internal fixation. METHODS: We retrospectively reviewed the records of patients with CSOTLF complicated with kyphosis who underwent posterior multilevel internal fixation in our hospital between January 2013 and January 2020. The patients' age, sex, body mass index (BMI), bone mineral density (BMD), smoking status, cause of injury, comorbidities, injury segments, and American Spinal Injury Association (ASIA) grading non-surgical data; posterior ligament complex (PLC) injury, upper and lower instrumented vertebral position (UIV and LIV, respectively), number of fixed segments surgical data, proximal junctional angle (PJA), sagittal vertebral axis (SVA), pelvic incidence (PI), lumbar lordosis (LL), pelvic incidence-lumbar lordosis mismatch (PI-LL), pelvic tilt (PT), and sacral slope (SS) surgical indicators were collected. Patients were divided into postoperative PJK and non-PJK groups. RESULTS: This study included 90 patients; among them, 30 (31.58%) developed PJK postoperatively. All patients were followed up for > 24 months (mean 32.5 months). Univariate analysis showed significant differences in age, BMI, BMD, PLC injury, UIV, and LIV fixation position, number of fixation stages, and preoperative PJA, SVA, PI-LL, and SS between the two groups (P < 0.05). Additionally, no significant differences were observed in sex, smoking, cause of injury, complications, injury segment ASIA grade, and preoperative PT between the two groups (P > 0.05). Multifactorial logistic regression analysis showed that age > 70 years (OR = 32.279, P < 0.05), BMI > 28 kg/m2 (OR = 7.876, P < 0.05), BMD T value < - 3.5 SD (OR = 20.836, P < 0.05), PLC injury (OR = 13.981, P < 0.05), and preoperative PI-LL > 20° (OR = 13.301, P < 0.05) were risk factors for PJK after posterior long-segment internal fixation in elderly patients with CSOTLF complicated with kyphosis. CONCLUSION: CSOTLF patients undergoing posterior long segment internal fixation are prone to PJK, and age > 70 years, BMI > 28 kg/m2, BMD T value < - 3.5 SD, preoperative PI-LL > 20° and PLC injury may increase their risk.


Assuntos
Cifose , Lordose , Fraturas por Osteoporose , Fusão Vertebral , Idoso , Humanos , Cifose/complicações , Cifose/cirurgia , Lordose/cirurgia , Vértebras Lombares/cirurgia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Fusão Vertebral/efeitos adversos , Vértebras Torácicas/cirurgia
7.
Eur Spine J ; 30(10): 3115-3127, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34392419

RESUMO

OBJECTIVE: We focus on providing the first comprehensive national dataset on the incidence, injury aetiology and mortality of TSCI in China. METHODS: A multi-stage stratified cluster sampling method was used. We included TSCI cases from all hospitals in three regions, nine provinces and 27 cities in China via search of electronic medical records and retrospectively analysed the characteristics of TSCI in China from 2009 to 2018. We estimated the incidence of TSCI in the total population and subgroups. RESULTS: There were 5954 actual cases in 2009, corresponding to a total estimated TSCI incidence of 45.1 cases per million population (95% CI, 44.0-46.3). There were 10,074 actual cases in 2018, corresponding to a total estimated TSCI incidence of 66.5 cases per million population (95% CI, 65.2-67.8) (P < 0.001; annual average percentage change (AAPC), 4.4%). From 2009 to 2018, the incidence of almost all sex/age groups showed an increasing trend over time (P < 0.001; AAPC, 0.7-8.8%). The elderly population (aged 65-74) displayed the highest incidence of TSCI (with an average annual incidence of 127.1 cases per million [95% CI, 119.8-134.3]). CONCLUSIONS: The TSCI incidence increased significantly from 2009 to 2018. The incidence in the elderly populations was consistently high and continues to increase over time. The mortality of TSCI patients in hospitals is relatively low and continues to decrease each year, but elderly individuals remain at a high risk of hospital death.


Assuntos
Traumatismos da Medula Espinal , Idoso , China/epidemiologia , Humanos , Incidência , Projetos de Pesquisa , Estudos Retrospectivos , Traumatismos da Medula Espinal/epidemiologia
8.
Spinal Cord ; 59(7): 804-813, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33268825

RESUMO

STUDY DESIGN: A hospital-based retrospective epidemiological study. OBJECTIVE: To describe the demographic and epidemiological characteristics of patients with traumatic spinal cord injury (TSCI) in Xi'an to help health-related institutions formulate corresponding measures. SETTING: People with TSCI, all spine centres and orthopaedic centres in Xi'an, China. METHODS: We retrospectively reviewed the medical records of the all spine centers or orthopedic centers in Xi'an according to the International Classification of Disease Version 10 (ICD-10) and diagnostic code of TSCI. Variables included gender, age, medical insurance, etiology, occupation, level of injury, and severity of injury, multiple injury, complication, treatment, and so on. RESULTS: The study included the medical records of 1730 patients with TSCI from 2014 to 2018. The estimated annual incidence rate increased from 39.0 cases (95% CI, 34.7-43.3 cases) per 1 million persons in 2014 to 43.2 cases (95% CI, 39.0-47.5 cases) per 1 million persons in 2018. The leading cause of TSCI was high falls (35.5%, 614 cases). The most common injury site was the cervical spinal cord, accounting for 55.7% (963 cases). The degree of injury severity with the highest proportion was incomplete tetraplegia (47.2%, 816 cases). In addition, 71.4% (1236 cases) of TSCI cases had spinal fracture or dislocation. CONCLUSIONS: There are specific epidemiological characteristics of TSCI patients in Xi'an, and preventive measures are suggested to be based on the characteristics of the different types of patients with TSCI and focused on high-risk groups.


Assuntos
Traumatismos da Medula Espinal , Acidentes por Quedas , China/epidemiologia , Humanos , Incidência , Estudos Retrospectivos , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/etiologia
9.
BMC Surg ; 21(1): 22, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407356

RESUMO

BACKGROUND: Symptomatic osteoporotic vertebral compression fractures (OVCF) are increasing, as are acute and chronic pain episodes and progressive spinal deformities. However, there are no clear surgical treatment criteria for patients with these different symptoms. Therefore, this study aims to explore the surgical approaches for the treatment of OVCF with different symptoms and evaluate the feasibility of these surgical approaches. METHODS: We retrospectively analyzed 238 symptomatic OVCF patients who entered our hospital from June 2013 to 2016. According to clinical characteristics and imaging examinations, these patients were divided into I-V grades and their corresponding surgical methods were developed. I, old vertebral fracture with no apparent instability, vertebral augmentation; II, old vertebral fracture with local instability, posterior reduction fusion internal fixation; III, old fractures with spinal stenosis, posterior decompression and reduction fusion and internal fixation; IV, old vertebral fracture with kyphosis, posterior osteotomy with internal fixation and fusion; V, a mixture of the above types, posterior osteotomy (decompression) with internal fixation and fusion. Postoperative visual analog score (VAS), oswestry disability index (ODI) scores, sagittal index (SI) and ASIA grades of neurological function were observed. RESULTS: All 238 patients were followed up for 12-38 months, with an average follow-up of 18.5 months. After graded surgery, the VAS score, ODI score, and vertebral sagittal index SI of 238 patients were significantly improved, and the difference between the last follow-up results and the preoperative comparison was statistically significant (P ˂ 0.05). Besides, the postoperative ASIA grades of 16 patients with nerve injury were improved from 14 patients with preoperative grade C, 2 patients with grade D to 4 patients with postoperative grade D and 12 patients with postoperative grade E. CONCLUSION: In this study, we concluded that graded surgery could better treat symptomatic old OVCF and restore spinal stability. This provides clinical reference and guidance for the treatment of symptomatic old OVCF in the future.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Fixação Interna de Fraturas , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento
10.
J Cell Mol Med ; 24(6): 3271-3281, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32045092

RESUMO

In the ageing skeleton, the balance of bone reconstruction could commonly be broken by the increasing of bone resorption and decreasing of bone formation. Consequently, the bone resorption gradually occupies a dominant status. During this imbalance process, osteoclast is unique cell linage act the bone resorptive biological activity, which is a highly differentiated ultimate cell derived from monocyte/macrophage. The erosive function of osteoclasts is that they have to adhere the bone matrix and migrate along it, in which adhesive cytoskeleton recombination of osteoclast is essential. In that, the podosome is a membrane binding microdomain organelle, based on dynamic actin, which forms a cytoskeleton superstructure connected with the plasma membrane. Otherwise, as the main adhesive protein, integrin regulates the formation of podosome and cytoskeleton, which collaborates with the various molecules including: c-Cbl, p130Cas , c-Src and Pyk2, through several signalling cascades cross talking, including: M-CSF and RANKL. In our current study, we discuss the role of integrin and associated molecules in osteoclastogenesis cytoskeletal, especially podosomes, regulation and relevant signalling cascades cross talking.


Assuntos
Reabsorção Óssea/metabolismo , Integrinas/metabolismo , Osteoclastos/metabolismo , Osteogênese/fisiologia , Podossomos/metabolismo , Animais , Citoesqueleto/metabolismo , Humanos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Ligante RANK/metabolismo , Transdução de Sinais/fisiologia , Quinase Syk/metabolismo
11.
Can J Physiol Pharmacol ; 98(10): 678-683, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32787688

RESUMO

This study investigated the effects of blockade of IL-6 on bone loss induced by modeled microgravity (MG). Adult male mice were exposed to hind-limb suspension (HLS) and treated with IL-6-neutralizing antibody (IL-6 nAb) for 4 weeks. HLS in mice led to upregulation of IL-6 expression in both sera and femurs. IL-6 nAb treatment in HLS mice significantly alleviated bone loss, evidenced by increased bone mineral density of whole tibia, trabecular thickness and number, bone volume fraction of proximal tibiae, and ultimate load and stiffness of femoral diaphysis. IL-6 nAb treatment in HLS mice significantly enhanced levels of osteocalcin in sera and reduced levels of deoxypyridinoline. In MC3T3-E1 cells exposed to MG in vitro, IL-6 nAb treatment increased mRNA expression and activity of alkaline phosphatase, mRNA expression of osteopontin and runt-related transcription factor 2, and protein levels of osteoprotegerin and decreased protein levels of receptor activator of the NF-κB ligand. In RAW254.7 cells exposed to MG, IL-6 nAb treatment downregulated mRNA expression of cathepsin K and tartrate-resistant acid phosphatase (TRAP) and reduced numbers of TRAP-positive multinucleated osteoclasts. In conclusion, blockade of IL-6 alleviated the bone loss induced by MG.


Assuntos
Anticorpos Neutralizantes/farmacologia , Conservadores da Densidade Óssea/farmacologia , Fêmur/efeitos dos fármacos , Interleucina-6/antagonistas & inibidores , Osteoporose/prevenção & controle , Tíbia/efeitos dos fármacos , Simulação de Ausência de Peso , Células 3T3 , Animais , Reatores Biológicos , Densidade Óssea/efeitos dos fármacos , Modelos Animais de Doenças , Fêmur/metabolismo , Regulação da Expressão Gênica , Elevação dos Membros Posteriores , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteoporose/etiologia , Osteoporose/genética , Osteoporose/metabolismo , Células RAW 264.7 , Transdução de Sinais , Tíbia/metabolismo
13.
J Cell Physiol ; 234(2): 1008-1015, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30145787

RESUMO

Melatonin's therapeutic potential has been highly underestimated because its biological functional roles are diverse and relevant mechanisms are complicated. Among the numerous biological activities of melatonin, its regulatory effects on pluripotent mesenchymal stem cells (MSCs), which are found in bone marrow stem cells (BMSCs) and adipose tissue (AD-MSC), have been recently proposed, which has received increasingly more attention in recent studies. Moreover, receptor-dependent and receptor-independent responses to melatonin are identified to occur in these cells by regulating signaling pathways, which drive the commitment and differentiation of MSCs into osteogenic, chondrogenic, or adipogenic lineages. Therefore, the aim of our current review is to summarize the evidence related to the utility of melatonin as a regulatory agent by focusing on its relationship with the differentiation of MSCs. In particular, we aimed to review its roles in promoting osteogenic and chondrogenic differentiation and the relevant signaling cascades involved. Also, the roles that melatonin and, particularly, its receptors play in these processes are highlighted.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Melatonina/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Animais , Células da Medula Óssea/metabolismo , Linhagem da Célula , Condrogênese/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Transdução de Sinais
14.
Can J Physiol Pharmacol ; 97(7): 655-660, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30870598

RESUMO

The present study was undertaken to explore the therapeutic potential of hydrogen sulfide against bone loss induced by modeled microgravity. Hindlimb suspension (HLS) and rotary wall vessel bioreactor were applied to model microgravity in vivo and in vitro, respectively. Treatment of rats with GYY4137 (a water soluble donor of hydrogen sulfide, 25 mg/kg per day, i.p.) attenuated HLS-induced reduction of bone mineral density in tibiae, and preserved bone structure in tibiae and mechanical strength in femurs. In HLS group, GYY4137 treatment significantly increased levels of osteocalcin in sera. Interestingly, treatment of HLS rats with GYY4137 enhanced osteoblast surface, but had no significant effect on osteoclast surface of proximal tibiae. In MC3T3-E1 cells exposed to modeled microgravity, GYY4137 stimulated transcriptional levels of runt-related transcription factor 2 and enhanced osteoblastic differentiation, as evidenced by increased mRNA expression and activity of alkaline phosphatase. HLS in rats led to enhanced levels of interleukin 6 in sera, skeletal muscle, and tibiae, which could be attenuated by GYY4137 treatment. Our study showed that GYY4137 preserved bone structure in rats exposed to HLS and promoted osteoblastic differentiation in MC3T3-E1 cells under modeled microgravity.


Assuntos
Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/etiologia , Sulfeto de Hidrogênio/metabolismo , Simulação de Ausência de Peso/efeitos adversos , Células 3T3 , Animais , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Sulfeto de Hidrogênio/sangue , Interleucina-6/metabolismo , Masculino , Camundongos , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Compostos Organotiofosforados/farmacologia , Compostos Organotiofosforados/uso terapêutico , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Ratos , Ratos Sprague-Dawley
15.
Med Sci Monit ; 25: 2479-2487, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30946733

RESUMO

BACKGROUND With the in-depth development of minimally invasive spine surgery in recent years, robot- and computer-assisted technologies have been increasingly used and successfully applied to spinal surgery. MATERIAL AND METHODS We performed a retrospective analysis of 60 patients with grade I or II lumbar spondylolisthesis who underwent minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) from January 2017 to December 2017. A robot-assisted surgical system was used in 30 patients for pedicle screw placement. The other 30 patients underwent fluoroscopy-guided percutaneous pedicle screw placement. RESULTS There were 130 screws placed under fluoroscopic guidance, with 26.2% penetration of the pedicle wall. There were 130 screws placed in robotic-assisted surgery, with 6.2% penetration of the pedicle wall. Severe screw deviation (Neo grade III) was identified in 4 screws in the fluoroscopy-guided group, while no severe deviation was noted in the robot-assisted group. In the fluoroscopic group, 15.6% of screws penetrated the superior articular process, and 2.1% screws had severe complications (Babu grade III). However, only 5.1% of screws in the robot-assisted group had severe complications. The mean screw insertion angle was significantly greater in the robot-assisted group than in the fluoroscopy-guided group (23.8±6.1° vs. 18.4±7.2°, P=0.017). CONCLUSIONS Compared to fluoroscopy-guided percutaneous pedicle screw placement, robot-assisted percutaneous pedicle screw placement has the following advantages: greater accuracy, lower incidences of screw penetration of the pedicle wall and invasion of the facet joints, and better screw insertion angle. Combined with MIS-TLIF, robot-assisted percutaneous pedicle screw placement is an effective minimally invasive treatment for lumbar spondylolisthesis.


Assuntos
Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Espondilolistese/cirurgia , Adulto , Idoso , China , Estudos de Coortes , Feminino , Humanos , Região Lombossacral/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Parafusos Pediculares , Estudos Retrospectivos , Robótica , Fusão Vertebral/métodos , Cirurgia Assistida por Computador/métodos , Resultado do Tratamento
16.
J Cell Mol Med ; 22(9): 4236-4242, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29911332

RESUMO

Myricitrin is a natural occurring flavonoid glycoside that possesses effects on inhibiting nitric oxide (NO) transmission and preventing inflammatory reaction. Although previous study showed the myricitrin possesses antibone loss effects via reducing the expression of IL-6 and partially suppressing reactive oxygen species (ROS) production. However, the effects of myricitrin on nuclear factor-kappaB ligand (RANKL)-stimulated osteoclastogenesis have not yet been further investigated. The current study was aimed to demonstrating the inhibitory effects of myricitrin on RANKL-stimulated osteoclastogenesis and relevant mechanisms. We found myricitrin significantly suppressed osteoclastogenesis suggesting that it may acts on RANKL/RANK induced downstream signal cross cascading in osteoclast precursors. In that, our Western blotting results showed myricitrin significantly attenuated RNAKL/MAPKs (phosphorylation of p38, ERK, JNK) and AKT signal cascading. Complementing previous study, our results suggesting as a natural inhibitor, myricitrin possesses the potential therapeutic effects on inflammatory osteolysis.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Flavonoides/farmacologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ligante RANK/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Diferenciação Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteogênese/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/antagonistas & inibidores , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
J BUON ; 23(5): 1534-1539, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30570882

RESUMO

PURPOSE: To explore whether the expression levels of matrix metalloproteinase-9 (MMP-9) are related to spinal metastasis of gastric carcinoma. METHODS: Fifty tissue specimens were collected from gastric carcinoma with spinal metastasis and set as test group A; 30 tissue specimens of primary gastric carcinoma were collected and set as control group B; 30 healthy paracancerous gastric tissue specimens were collected and set as control group C. The expression levels of MMP-9 and vascular endothelial growth factor (VEGF) in the specimens were analyzed by immunohistochemistry. RESULTS: The positive expression rates of MMP-9 in the three groups were 82.0, 63.33 and 16.67% respectively, and the positive expression rates of VEGF were 78.00, 56.67 and 13.33%, respectively. The positive expression rates of MMP-9 and VEGF in the test group A were statistically significantly higher than those of control group B and C (p<0.05). These findings suggest a positive correlation between MMP-9 and VEGF expression. CONCLUSION: Increased expression of MMP-9 is associated with the spinal metastasis of gastric carcinoma.


Assuntos
Metaloproteinase 9 da Matriz/biossíntese , Neoplasias da Coluna Vertebral/enzimologia , Neoplasias da Coluna Vertebral/secundário , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias da Coluna Vertebral/patologia
18.
Eur Spine J ; 26(4): 1058-1063, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27246351

RESUMO

BACKGROUND: Ponticulus posticus is a common anatomic variation that can be mistaken for a broad posterior arch during C1 pedicle screw placement. When the atlas lateral mass screws are placed via the posterior arch, injury to the vertebral artery may result. To our knowledge, there are few clinical studies that have analyzed the feasibility of C1 pedicle screw fixation in patients with ponticulus posticus, in clinical practice. PURPOSE: To evaluate the feasibility of inserting a C1 pedicle screw in patients with ponticulus posticus. METHODS: Between January 2008 and January 2012, 11 consecutive patients with atlantoaxial instability, and with a ponticulus posticus at C1, underwent posterior fusion surgery in our institution. According to preoperative computed tomography (CT) reconstruction, a complete ponticulus posticus was found unilaterally in nine patients and bilaterally in two. Postoperative CT reconstructive imaging was performed to assess whether C1 pedicle screw placement was successful. Patients were followed up at regular intervals and evaluated for symptoms of ponticulus posticus syndrome. RESULTS: Thirteen C1 pedicles (atlas vertebral artery groove), each with a complete ponticulus posticus, were successfully inserted with thirteen 3.5- or 4.0-mm diameter pedicle screws, without resection of the bony anomaly. No intraoperative complications (venous plexus, vertebral artery, or spinal cord injury) occurred. The mean follow-up period was 21 (range 14-30) months. Postoperative CT reconstructive images showed that all 13 pedicle screws were inserted in the C1 pedicles without destruction of the atlas pedicle cortical bone. In the follow-up period, none of the patients demonstrated clinical symptoms of ponticulus posticus syndrome or developed bone fusion. CONCLUSION: Three-dimensional CT imaging should be considered prior to C1 pedicle screw fixation in patients with ponticulus posticus, to avoid mistaking the ponticulus posticus for a widened dorsal arch of the atlas. If there is no ponticulus posticus syndrome preoperatively, C1 pedicle screw fixation can be successfully performed without removing the bony anomaly.


Assuntos
Atlas Cervical , Parafusos Pediculares , Atlas Cervical/diagnóstico por imagem , Atlas Cervical/cirurgia , Estudos de Viabilidade , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
19.
BMC Musculoskelet Disord ; 18(1): 81, 2017 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-28196468

RESUMO

BACKGROUND: The most common site of fractures in patients with ankylosing spondylitis (AS) is the cervical spine, especially the lower cervical spine and cervicothoracic junction. The optimal treatment for cervical spine fractures secondary to AS is controversial. This study aimed to explore the effects of posterior pedicle screw fixation alone on fractures of the lower cervical spine in patients with AS. METHODS: From January 2006 to January 2013, a total of 35 patients with AS and a lower cervical spine fracture were treated using only posterior cervical/thoracic pedicle screw fixation. In this retrospective study, we reviewed the patients' charts to assess their case histories, operations, neurological outcomes, and complications. We also evaluated their postoperative radiographs to determine the time of bone fusion. RESULTS: Altogether, 32 (91.4%) of the 35 fractures resulted from an acute injury and 3 (8.6%) from a chronic injury. In 25 cases, the fracture resulted from a low-energy spinal injury and in 8 cases from a high-energy injury. Posterior pedicle screw fixation was successful in all patients, with radiographic fusion confirmed by computed tomography. The average time of bone fusion was 3.6 months (range 3 - 6 months). The surgery improved the American Spinal Injury Association grade in 15 (42.9%) patients. No intraoperative complications occurred. None of the corrections resulted in neurological decompensation. The average postoperative correction was 18°. CONCLUSIONS: Pedicle screw fixation and autologous bone grafting through a single posterior approach to lower cervical spine fractures in AS patients could stabilize the spine, correct kyphosis, and relieve pressure. It is thus reasonable to recommend this surgical strategy for AS-associated fractures of the lower cervical spine. TRIAL REGISTRATION: Not applicable.


Assuntos
Vértebras Cervicais/lesões , Fixação Interna de Fraturas/instrumentação , Fraturas da Coluna Vertebral/cirurgia , Espondilite Anquilosante/complicações , Adulto , Idoso , Parafusos Ósseos , Vértebras Cervicais/cirurgia , Feminino , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fraturas da Coluna Vertebral/etiologia
20.
BMC Surg ; 17(1): 113, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29183306

RESUMO

BACKGROUND: ACDF has been considered as the gold standard in the treatment of single level cervical disk protrusion. However, it may cause adjacent level degeneration due to regional biomechanical changes. TDR has been applied with satisfactory results for over a decade, but there is no consensus if TDR is safer and more efficient than ACDF. The current study was carried out to compare the efficiency and safety of TDR and ACDF in the treatment of patients with single level cervical disk protrusion. METHODS: One hundred forty-five consecutive patients who underwent either TDR or ACDF in our center were included in the current study. Time of surgery, intraoperative blood loss, VAS arm and neck pain scores, ROM, ODI, SF36 and Patient satisfaction were compared before the surgery, after the surgery, and during follow up 1, 3, 5, 8 years after the surgery. RESULTS: The time of surgery was 64.6 ± 20.7 min in the ACDF group and 69.4 ± 19.3 min in the TDR group; intraoperative hemorrhage was 67.2 ± 14.3 ml in ACDF group and 70.7 ± 18.6 ml in TDR group. There were no significant differences between two groups concerning time of surgery and intraoperative blood loss. No differences were found concerning patient satisfaction between the two groups during the follow up (P > 0.05). Significant differences were found between the groups concerning VAS arm and neck pain scores, ROM, ODI and SF36 after the surgery and during the 8 year follow up. CONCLUSION: TDR may be a more effective approach than ACDF for treating patients with single level cervical disk protrusion.


Assuntos
Discotomia/métodos , Fusão Vertebral/métodos , Espondilose/cirurgia , Substituição Total de Disco/métodos , Adulto , Perda Sanguínea Cirúrgica , Vértebras Cervicais/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Satisfação do Paciente , Estudos Retrospectivos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA