Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
1.
J Oral Rehabil ; 51(6): 924-930, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38356183

RESUMO

OBJECTIVE: To examine the association between rheumatoid arthritis (RA) and oral hypofunction (OHF) using propensity score matching (PSM) to adjust for differences between older adults with RA and the general older adult population. METHODS: We conducted a cross-sectional survey among 189 older adults with RA in 2019 (mean age, 71.9 ± 3.6) and 47 178 independent older adult residents in 2016 (mean age, 71.6 ± 4.0), respectively. The questionnaire covered information on socio-demographic characteristics and OHF for both groups. Age, sex, educational level and smoking history were used to determine PSM. Prevalence ratios (PRs) and 95% confidence intervals (CIs) of self-reported OHF (fewer remaining teeth, decreased masticatory function, deterioration of swallowing function and oral dryness) were estimated using Poisson regressions. RESULT: OHF was observed in 44.4% of patients with RA and 27.5% of residents. Before PSM, the prevalence of OHF among patients with RA was higher than that of residents (PR, 1.75; 95% CI, 1.50-2.05). After PSM, there were 189 patients with RA and residents, and the prevalence of OHF among patients with RA was still higher (PR, 1.61; 95% CI, 1.22-2.13). Poisson regression showed that the prevalence of 19 or fewer teeth (PR, 1.06; 95% CI, 0.82-1.36), difficulties eating tough foods (PR, 1.18; 95% CI, 0.90-1.55), difficulties swallowing tea or soup (PR, 1.77; 95% CI, 1.19-2.63), and dry mouth (PR, 2.79; 95% CI, 1.90-4.07) was higher among patients with RA than residents. CONCLUSION: Compared with the general older adult population, patients with RA have a higher prevalence of self-reported OHF.


Assuntos
Artrite Reumatoide , Pontuação de Propensão , Autorrelato , Humanos , Estudos Transversais , Feminino , Masculino , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/complicações , Idoso , Prevalência , Xerostomia/epidemiologia , Idoso de 80 Anos ou mais , Inquéritos e Questionários
2.
J Pharmacol Sci ; 151(1): 1-8, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36522118

RESUMO

Bone remodeling mediated by bone-forming osteoblasts (OBs) and bone-resorbing osteoclasts (OCs) maintains bone structure and function. Excessive OC activation leads to bone-destroying diseases such as osteoporosis and bone erosion of rheumatoid arthritis (RA). Differentiation of OCs from bone marrow cells (BMCs) is regulated by the bone microenvironment. The proinflammatory cytokine interleukin (IL)-1ß reportedly enhances osteoclastogenesis and plays important roles in RA-associated bone loss. The present study investigated the effect of IL-1ß on OC formation via microenvironmental cells. Treating mouse BMCs with IL-1ß in the presence of receptor activator of NF-κB ligand and macrophage colony-stimulating factor increased the number of OCs. Real-time RT-PCR revealed increased expression of the IL-1ß, IL-1RI, and IL-1RII genes in non-OCs compared with OCs. Removing CD45- cells which cannot differentiate into OCs, from mouse BMCs reduced the IL-1ß-mediated enhancement of osteoclastogenesis. IL-1ß treatment upregulated the expression of inducible nitric oxide synthase, insulin-like growth factor 2 (IGF2), and the chemokines stromal cell derived factor 1, C-X3-C motif ligand 1 (CX3CL1), and CXCL7 in non-OCs. Neutralizing antibodies against these chemokines and IGF2 suppressed osteoclastogenesis in the presence of IL-1ß. These results suggest that IL-1ß enhances osteoclastogenesis by upregulating IGF2 and chemokine expression in non-OCs.


Assuntos
Osteoclastos , Osteogênese , Camundongos , Animais , Osteogênese/genética , Ligantes , Células Cultivadas , Osteoclastos/metabolismo , Osteoblastos/metabolismo , Diferenciação Celular/genética , Ligante RANK/genética , Ligante RANK/metabolismo
3.
Mod Rheumatol ; 33(2): 271-278, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35389481

RESUMO

OBJECTIVES: We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. METHODS: Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. RESULTS: At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. CONCLUSION: The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Humanos , Metotrexato/efeitos adversos , Abatacepte/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Resultado do Tratamento , Quimioterapia Combinada , Produtos Biológicos/uso terapêutico
4.
Am J Pathol ; 191(12): 2072-2079, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34560064

RESUMO

Bone homeostasis depends on the balance between bone resorption by osteoclasts (OCs) and bone formation by osteoblasts. Bone resorption can become excessive under various pathologic conditions, including rheumatoid arthritis. Previous studies have shown that OC formation is promoted under hypoxia. However, the precise mechanisms behind OC formation under hypoxia have not been elucidated. The present study investigated the role of inducible nitric oxide synthase (iNOS) in OC differentiation under hypoxia. Primary bone marrow cells obtained from mice were stimulated with receptor activator of NF-κB ligand and macrophage colony-stimulating factor to induce OC differentiation. The number of OCs increased in culture under hypoxia (oxygen concentration, 5%) compared with that under normoxia (oxygen concentration, 20%). iNOS gene and protein expression increased in culture under hypoxia. Addition of an iNOS inhibitor under hypoxic conditions suppressed osteoclastogenesis. Addition of a nitric oxide donor to the normoxic culture promoted osteoclastogenesis. Furthermore, insulin-like growth factor 2 expression was significantly altered in both iNOS inhibition experiments and nitric oxide donor experiments. These data might provide clues to therapies for excessive osteoclastogenesis under several hypoxic pathologic conditions, including rheumatoid arthritis.


Assuntos
Hipóxia Celular/fisiologia , Óxido Nítrico Sintase Tipo II/fisiologia , Osteoclastos/fisiologia , Animais , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Hipóxia Celular/efeitos dos fármacos , Células Cultivadas , Indução Enzimática/efeitos dos fármacos , Indução Enzimática/genética , Hipóxia/genética , Hipóxia/metabolismo , Hipóxia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Oxigênio/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , ômega-N-Metilarginina/farmacologia
5.
J Pharmacol Sci ; 149(3): 93-99, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35641033

RESUMO

Osteoporosis is caused by an imbalance in bone remodeling due to abnormal osteoclast (OC) formation and activation. Hypoxia at the site of inflammation promotes OC formation and activation in various species, including humans. We previously reported that insulin-like growth factor 2 (IGF2) plays an important role in osteoclastogenesis under hypoxia. In our present study, we focused on the mechanism of osteoclastogenesis in regard to IGF2 signaling under hypoxia. We confirmed that the addition of IGF2 promoted osteoclastogenesis under normoxic conditions. Conversely, IGF2-neutralizing antibodies inhibited osteoclastogenesis under both normoxic and hypoxic conditions. IGF2 addition increased levels of phosphorylated Akt (Thr308 and Ser473) and NF-κB (Ser536), indicating activation of the Akt-NF-κB pathway. IGF2 also increased the expression of inducible nitric oxide synthase, which promotes osteoclastogenesis via nitric oxide production. Expression levels of genes encoding inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6, were upregulated, indicating that IGF2 promotes osteoclastogenesis by increasing the expression of inflammatory cytokines via activation of the Akt-NF-κB pathway. These results suggest that IGF2 is a promising therapeutic target for osteoporosis and rheumatoid arthritis.


Assuntos
Citocinas , Hipóxia , Fator de Crescimento Insulin-Like II , Osteogênese , Citocinas/metabolismo , Humanos , Fator de Crescimento Insulin-Like II/metabolismo , NF-kappa B/metabolismo , Osteoporose , Proteínas Proto-Oncogênicas c-akt
6.
Exp Cell Res ; 404(1): 112630, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33971195

RESUMO

The proximal tubules, which are part of the kidney, maintain blood homeostasis by absorbing amino acids, glucose, water, and ions such as sodium (Na), potassium, and bicarbonate. Proximal tubule dysfunction is associated with the pathogenesis of many kidney diseases. Renal proximal tubular epithelial cells (RPTECs) are responsible for the main functions of the proximal tubules. Therefore, in vitro experiments using RPTECs would greatly enhance our understanding of nephron physiology and pathobiology. It is preferable to use immortalized cell lines, such as human kidney-2 (HK-2) cells, because they are derived from humans and maintain growth indefinitely. However, tissue-specific RPTEC phenotypes, including apical-basal polarization, are frequently lost in conventional two-dimensional culture methods in part due to microenvironmental deficiencies. To overcome this limitation, we developed a three-dimensional (3D) spheroid culture method for HK-2 cells using an extracellular matrix. HK-2 spheroids in 3D culture formed a tubule-like architecture with cellular polarity and showed markedly restored Na transport function. 3D culture of HK-2 cells also increased expression of kidney development-related genes, including WNT9B. Models of human renal tubules using HK-2 spheroids will greatly improve our understanding of the physiology and pathobiology of the kidney.


Assuntos
Polaridade Celular/fisiologia , Células Epiteliais/citologia , Túbulos Renais Proximais/citologia , Túbulos Renais/metabolismo , Transporte Biológico , Linhagem Celular , Matriz Extracelular/metabolismo , Humanos , Rim/metabolismo , Sódio/metabolismo
7.
J Orthop Sci ; 27(6): 1271-1277, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34404612

RESUMO

BACKGROUND: Meniscal ramp lesion (RL) is the peripheral lesion of the posterior horn of the medial meniscus (PHMM) associated with anterior cruciate ligament (ACL) tear. The purpose of this study was to evaluate the accuracy of pre-operative magnetic resonance imaging (MRI) evaluation in diagnosing RL and to identify whether the difficulty in diagnosis differs depending on the location of RL. METHODS: ACL-injured patients undergoing ACL reconstruction from January 2017 to January 2019 were enrolled. A methodical arthroscopic exploration to identify RL was conducted intra-operatively using three steps, namely, the anterior visualization step, the inter-condylar visualization step, and the posteromedial step. The location of the RLs was evaluated and classified into two types as follows: Red-red zone (RR) - a meniscal tear of the red-red zone of the PHMM. Menisco-capsular junction (MCJ) - a lesion at the menisco-capsular junction of the PHMM, which is more peripheral than RR. Furthermore, the accuracy of 1.5-T MRI evaluation to diagnose RL by two testers using sagittal proton-density fat-saturated images was calculated. RESULTS: Of the 81 patients enrolled, 11 had RL: 5 cases each were at the MCJ and RR, and 1 case was at both locations. The sensitivity of MRI for detecting RL was 27.3-45.5%, whereas the specificity was 84.3-95.7% in total. The sensitivity of MRI in detecting RL at the RR and MCJ was 40.0-80.0%, 0-20.0%, respectively. The intra-observer reliability of the MRI evaluation was moderate (κ coefficient: 0.40-0.46), while the inter-observer reliability was fair to moderate (κ coefficient: 0.27-0.41). CONCLUSIONS: A low sensitivity of the MRI in detecting RL at the MCJ was observed, and the reliability of the MRI evaluation for diagnosis of RL was not high. Therefore, methodical arthroscopic exploration is essential to diagnose RL even when it is not suspected on pre-operative MRI.


Assuntos
Lesões do Ligamento Cruzado Anterior , Lesões do Menisco Tibial , Humanos , Meniscos Tibiais/cirurgia , Lesões do Menisco Tibial/diagnóstico por imagem , Lesões do Menisco Tibial/cirurgia , Lesões do Menisco Tibial/complicações , Reprodutibilidade dos Testes , Artroscopia/métodos , Lesões do Ligamento Cruzado Anterior/cirurgia , Imageamento por Ressonância Magnética
8.
Mod Rheumatol ; 32(3): 528-533, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-34894248

RESUMO

OBJECTIVES: We aimed to examine the psychosocial characteristics of patients with rheumatoid arthritis (RA) by remission status and determine the impacts of social support on severity of depressive symptoms. METHODS: We enrolled RA patients aged 40-79 years who visited university hospitals' outpatient clinics. Severity of depressive symptoms (Beck Depression Inventory-II), physical disability (Health Assessment Questionnaire), and support were evaluated. Furthermore, RA disease activity was evaluated by 28-point Disease Activity Score (DAS28) calculation. The independent impacts of instrumental and emotional social support on depressive symptoms by remission status defined as DAS28 score < 2.6 were estimated by multivariable regression analysis. RESULTS: This study included 360 RA patients. In the remission group, emotional support showed a statistically significant negative impact on depressive symptoms, whereas instrumental support had an extremely limited contribution to severity of depressive symptoms. In the non-remission group, instrumental support showed a negative tendency of impact on severity of depressive symptoms, whereas emotional support had a wide range of influence. CONCLUSIONS: Favourable association between emotional support and depressive symptoms is confirmed only among RA patients in remission status. The influence of emotional support in non-remission patients and that of instrumental support regardless of remission status are inconclusive.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Depressão/etiologia , Depressão/psicologia , Humanos , Indução de Remissão , Índice de Gravidade de Doença , Apoio Social
9.
Mod Rheumatol ; 31(5): 979-986, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33066713

RESUMO

OBJECTIVES: To investigate the clinical and psychosocial backgrounds of frailty in rheumatoid arthritis (RA) patients. METHODS: Patients with RA between 40 and 79 years of age who visited university hospitals in an urban area were recruited. Well-validated self-reported questionnaires were used to evaluate patient physical function (Health Assessment Questionnaire, HAQ), depressive symptoms (Beck Depression Inventory-II, BDI-II), and frailty (Kihon Checklist). A 28-point Disease Activity Score (DAS-28) was calculated to evaluate RA disease activity. RESULTS: A total of 375 RA patients, 323 of whom were women, were enrolled (average age: 65.2 ± 9.7 years; average disease duration: 16.6 ± 11.9 years). The prevalence rates of frailty, working-age (40-64 years), young-old (65-74 years), and old-old (≥75 years) patients were 18.5, 28.8, and 36.6%, respectively. Higher age and longer disease duration were associated with frailty. Multivariable logistic regression analysis revealed that HAQ, DAS-28, and BDI-II scores were independently associated with frailty in RA patients. CONCLUSION: Frailty is common, even among working-age RA patients. Physical function, disease activity, and depressive symptoms were independently associated with frailty. A multidisciplinary intervention approach, along with adequate pharmacological therapy, may promote successful aging in patients with RA.


Assuntos
Artrite Reumatoide , Fragilidade , Adulto , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Depressão/complicações , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Fragilidade/complicações , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários
10.
Clin Exp Rheumatol ; 36(4): 559-567, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29352846

RESUMO

OBJECTIVES: Gliostatin (GLS) is known to have angiogenic and arthritogenic activity, and GLS expression levels in serum from patients with rheumatoid arthritis (RA) are significantly correlated with the disease activity. Tofacitinib is a novel oral Janus kinase (JAK) inhibitor and is effective in treating RA. However, the mechanism of action of tofacitinib in fibroblast-like synoviocytes (FLSs) has not been elucidated. The purpose of this study was to investigate the modulatory effects of tofacitinib on serum GLS levels in patients with RA and GLS production in FLSs derived from patients with RA. METHODS: Six patients with RA who had failed therapy with at least one TNF inhibitor and were receiving tofacitinib therapy were included in the study. Serum samples were collected to measure CRP, MMP-3 and GLS expression. FLSs derived from patients with RA were cultured and stimulated by TNFα with or without tofacitinib. GLS expression levels were determined using reverse transcription-polymerase chain reaction (RT-PCR), EIA and immunocytochemistry, and signal transducer and activator of transcription (STAT) protein phosphorylation levels were determined by western blotting. RESULTS: Treatment with tofacitinib decreased serum GLS levels in all patients. GLS mRNA and protein expression levels were significantly increased by treatment with TNF-α alone, and these increases were suppressed by treatment with tofacitinib, which also inhibited TNF-α-induced STAT1 phosphorylation. CONCLUSIONS: JAK/STAT activation plays a pivotal role in TNF-α-mediated GLS up-regulation in RA. Suppression of GLS expression in FLSs has been suggested to be one of the mechanisms through which tofacitinib exerts its anti-inflammatory effects.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Inibidores de Janus Quinases/farmacologia , Piperidinas/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Sinoviócitos/metabolismo , Timidina Fosforilase/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibroblastos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Fator de Transcrição STAT1/metabolismo
11.
BMC Musculoskelet Disord ; 19(1): 268, 2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30053808

RESUMO

BACKGROUND: Although aneurysmal bone cysts (ABCs) are benign tumours, they have the potential to be locally aggressive. Various treatment approaches, such as en bloc resection, open curettage, radiotherapy, sclerotherapy, and embolization have been proposed, but the most appropriate treatment should be selected after considering the risk of tumour recurrence and treatment complications. Endoscopic curettage (ESC) may be a less invasive alternative to open curettage for ABC treatment. We aimed to describe the use of ESC for the treatment of ABCs and to report our clinical outcomes, including the incidence rate of recurrence, radiological appearance at final follow-up, time to solid union, complications, and postoperative function. METHODS: Between 1998 and 2015, 30 patients (18 men and 12 women; mean age, 17.4 years) underwent ESC for the treatment of primary ABCs at our hospital (mean postoperative follow-up, 55 months). ESC was performed under arthroscopic guidance for direct visualization, and curettage extended until normal bone was observed in the medullary cavity. To investigate bone healing after ESC, we evaluated the consolidation of cysts at the final evaluation (based on the modified Neer classification) and time to solid union after surgery, which was defined as sufficient cortical bone thickness to prevent fracture and allow physical activities. RESULTS: Recurrence was identified in 3 cases (10%). Curative outcomes were obtained after repeated ESC or open curettage. A log-rank analysis indicated that age < 10 years (p = 0.004) and contact of the tumour with the physis (p = 0.01) increased the risk of tumour recurrence. Residual tumours were identified in 9 cases (30%); these lesions remained inactive over the extended follow-up period. The average time to solid union after endoscopic curettage was 3.2 months. Transient radial nerve palsy was identified in 1 case. Good postoperative functional recovery occurred in all cases. CONCLUSIONS: ESC is a minimally invasive technique for the treatment of ABCs, and the tumour recurrence rate is comparable to that of other standard procedures. However, the application of this method should be carefully considered, especially for patients < 10 years and when the tumour comes in contact with the physis.


Assuntos
Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/cirurgia , Curetagem/métodos , Endoscopia/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Adulto Jovem
12.
Mod Rheumatol ; 28(3): 495-505, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28741989

RESUMO

OBJECTIVES: Gliostatin (GLS) has angiogenic and arthritogenic activities and enzymatic activity as thymidine phosphorylase. Aberrant GLS production has been observed in the synovial membranes of patients with rheumatoid arthritis (RA). Matrix metalloproteinases (MMPs) are involved in joint destruction. Promoters of GLS and some MMP genes contain Sp1 binding sites. We examined the inhibitory effect of the Sp1 inhibitor mithramycin on GLS-induced GLS and MMP expression in cultured fibroblast-like synoviocytes (FLSs). METHODS: Synovial tissue samples were obtained from patients with RA. FLSs pretreated with mithramycin were cultured with GLS. The mRNA expression levels of GLS and MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13 were determined using reverse transcription polymerase chain reactions. Protein levels were measured using enzyme immunoassay and gelatin zymography. RESULTS: GLS upregulated the expression of GLS itself and of MMP-1, MMP-3, MMP-9, and MMP-13, an effect significantly reduced by treatment with mithramycin. GLS and mithramycin had no effect on MMP-2 expression. CONCLUSIONS: Mithramycin downregulated the increased expression of GLS and MMP-1, MMP-3, MMP-9, and MMP-13 in FLSs treated with GLS. Because GLS plays a pathological role in RA, blocking GLS stimulation using an agent such as mithramycin may be a novel approach to antirheumatic therapy.


Assuntos
Artrite Reumatoide/metabolismo , Metaloproteinases da Matriz/metabolismo , Plicamicina/farmacologia , Sinoviócitos/efeitos dos fármacos , Timidina Fosforilase/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/farmacologia , Artrite Reumatoide/patologia , Células Cultivadas , Feminino , Humanos , Masculino , Metaloproteinases da Matriz/genética , Pessoa de Meia-Idade , Sinoviócitos/metabolismo , Timidina Fosforilase/genética
13.
Stem Cells ; 34(11): 2733-2743, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27339271

RESUMO

Bone homeostasis comprises the balance between bone-forming osteoblasts and bone-resorbing osteoclasts (OCs), with an acceleration of osteoclastic bone resorption leading to osteoporosis. OCs can be generated from bone marrow cells (BMCs) under the tightly regulated local bone environment. However, it remained difficult to identify the critical cells responsible for providing an osteoclastogenesis niche. In this study, we used a fluorescence-activated cell sorting technique to determine the cell populations important for forming an appropriate microenvironment for osteoclastogenesis and to verify the associated interactions between osteoclast precursor cells and non-OCs. We isolated and removed a small cell population specific for osteoclastogenesis (CXCR4+ CD45- ) from mouse BMCs and cultured the remaining cells with receptor activator of nuclear factor-kappa B ligand (RANKL) and macrophage-colony stimulating factor. The resulting cultures showed significantly less large osteoclast formation. Quantitative RT-PCR analysis revealed that these CXCR4+ CD45- cells expressed low levels of RANK and RANKL, but high levels of critical chemokines including stromal cell derived factor 1 (SDF-1), chemokine (C-X-C motif) ligand 7 (CXCL7), and chemokine (C-X3-C motif) ligand 1 (CX3CL1). Furthermore, an SDF-1-specific antibody strongly suppressed OC formation in RAW264.7 cells and antibodies against SDF-1, CXCL7, and CX3CL1 suppressed OC formation in BMCs. These results suggest that isolated CXCR4+ CD45- cells support an appropriate microenvironment for osteoclastogenesis with a direct effect on the cells expressing SDF-1, CXCL7, and CX3CL1 receptors. The regulation of CXCR4+ CD45- cell function might therefore inform therapeutic strategies for diseases involving loss of bone homeostasis. Stem Cells 2016;34:2733-2743.


Assuntos
Quimiocina CX3CL1/genética , Quimiocina CXCL12/genética , Quimiocinas CXC/genética , Antígenos Comuns de Leucócito/genética , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Receptores CXCR4/genética , Animais , Anticorpos/farmacologia , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Diferenciação Celular , Quimiocina CX3CL1/metabolismo , Quimiocina CXCL12/antagonistas & inibidores , Quimiocina CXCL12/metabolismo , Quimiocinas CXC/metabolismo , Citometria de Fluxo , Regulação da Expressão Gênica , Antígenos Comuns de Leucócito/deficiência , Fator Estimulador de Colônias de Macrófagos/farmacologia , Masculino , Camundongos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteogênese/genética , Cultura Primária de Células , Ligante RANK/genética , Ligante RANK/metabolismo , Ligante RANK/farmacologia , Receptor Ativador de Fator Nuclear kappa-B/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais , Tíbia/citologia , Tíbia/efeitos dos fármacos , Tíbia/metabolismo
14.
J Orthop Sci ; 22(5): 874-879, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28559103

RESUMO

BACKGROUND: Recently several authors have reported on the quantitative evaluation of the pivot-shift test using cutaneous fixation of inertial sensors. Before utilizing this sensor for clinical studies, it is necessary to evaluate the accuracy of cutaneous sensor in assessing rotational knee instability. To evaluate the accuracy of inertial sensors, we compared cutaneous and transosseous sensors in the quantitative assessment of rotational knee instability in a cadaveric setting, in order to demonstrate their clinical applicability. METHODS: Eight freshly frozen human cadaveric knees were used in this study. Inertial sensors were fixed on the tibial tuberosity and directly fixed to the distal tibia bone. A single examiner performed the pivot shift test from flexion to extension on the intact knees and ACL deficient knees. The peak overall magnitude of acceleration and the maximum rotational angular velocity in the tibial superoinferior axis was repeatedly measured with the inertial sensor during the pivot shift test. Correlations between cutaneous and transosseous inertial sensors were evaluated, as well as statistical analysis for differences between ACL intact and ACL deficient knees. RESULTS: Acceleration and angular velocity measured with the cutaneous sensor demonstrated a strong positive correlation with the transosseous sensor (r = 0.86 and r = 0.83). Comparison between cutaneous and transosseous sensor indicated significant difference for the peak overall magnitude of acceleration (cutaneous: 10.3 ± 5.2 m/s2, transosseous: 14.3 ± 7.6 m/s2, P < 0.01) and for the maximum internal rotation angular velocity (cutaneous: 189.5 ± 99.6 deg/s, transosseous: 225.1 ± 103.3 deg/s, P < 0.05), but no significant difference for the maximum external rotation angular velocity (cutaneous: 176.1 ± 87.3 deg/s, transosseous: 195.9 ± 106.2 deg/s, N.S). CONCLUSIONS: There is a positive correlation between cutaneous and transosseous inertial sensors. Therefore, this study indicated that the cutaneous inertial sensors could be used clinically for quantifying rotational knee instability, irrespective of the location of utilization.


Assuntos
Ligamento Cruzado Anterior/fisiopatologia , Instabilidade Articular/diagnóstico , Articulação do Joelho , Exame Físico/instrumentação , Exame Físico/métodos , Idoso , Idoso de 80 Anos ou mais , Cadáver , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Rotação
15.
Exp Cell Res ; 321(2): 167-77, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24360989

RESUMO

Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. In this study, we used human bone marrow cells (BMCs) to investigate the role of hypoxic exposure on human osteoclast (OC) formation in the presence of tumor necrosis factor (TNF). Exposing the BMCs to 3%, 5%, or 10% O2 in the presence of receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) generated tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells, consistent with OCs. The addition of TNF under hypoxic conditions generated significantly greater numbers of mature OCs with more nuclei than OCs generated under normoxic conditions. Longer initial hypoxic exposure increased the number of OC precursor cells and facilitated the differentiation of OC precursor cells into multinucleated OCs. Quantitative RT-PCR analysis revealed that RANKL and TNFR1 were expressed at higher levels in non-OC cells from BMCs under hypoxic conditions than under normoxic conditions. Furthermore, to confirm the involvement of TNF-induced signaling, we examined the effects of blocking antibodies against TNFR1 and TNFR2 on OC formation under hypoxic conditions. The TNFR1 antibody was observed to significantly suppress OC formation. These results suggest that hypoxic exposure plays an important role in TNF-induced osteoclastogenesis from human BMCs.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Células da Medula Óssea/fisiologia , Hipóxia Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Osteoclastos/fisiologia , Oxigênio/farmacologia , Consumo de Oxigênio/fisiologia , Fatores de Tempo
16.
J Orthop Sci ; 20(5): 823-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26169109

RESUMO

PURPOSE: This study investigated the direct and continuous attachment of the labrum to the glenoid fossa, including the fibrocartilaginous tissue, using image-analysis software and histology. METHODS: Twenty-six cadaveric shoulders (11 male, 15 female; mean age 80.1 years; age range 36-103 years) were used. The glenoid of each specimen was divided into six pie-slice-shaped pieces from the center perpendicular to the articular surface by radial incisions at the 2, 4, 6, 8, 10, and 12 o'clock positions. The general distribution of the labrum, including the fibrocartilage, was assessed in hematoxylin and eosin-, Safranin O- and Azan-Mallory-stained sections. The continuous length of attachment of the labrum to the glenoid was measured using image-analysis software. The width of attachment to the articular surface of the glenoid was assessed in each position. RESULTS: The labrum attached to both the articular surface and the neck of the glenoid in all shoulders (100 %) in the 4 and 6 o'clock positions. The mean length of the entire attachment to the glenoid was 4.6 mm (range 3.2-6.1 mm). The width of attachment from the bony edge of the glenoid to the edge of the labrum on the articular surface ranged from 0 to 4.3 mm. The length of the entire attachment of the labrum was shortest in the 2 o'clock position (p = 0.229). Additionally, the length of the entire attachment of the labrum was longest in the 4 o'clock position. The width of attachment to the articular surface of the glenoid was greatest in the 4 o'clock position (p < 0.01). CONCLUSION: In the 4 and 6 o'clock positions, the labrum attached to both the articular surface and neck of the glenoid in all of the shoulders (100 %). The length of the entire attachment to the labrum, including the fibrocartilage, was shortest in the 2 o'clock position. The width of attachment to the articular surface of the glenoid was greatest in the 4 o'clock position (p < 0.01).


Assuntos
Cavidade Glenoide/anatomia & histologia , Escápula/anatomia & histologia , Articulação do Ombro/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Fibrocartilagem/citologia , Humanos , Masculino , Pessoa de Meia-Idade
17.
J Orthop Sci ; 20(3): 481-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25743369

RESUMO

BACKGROUND: Here we investigated the angle and placement of bone holes for suture anchors using postoperative computed-tomography scapula scans. METHODS: The study group comprised 20 shoulders from 20 consecutive patients (13 males and seven females; mean age 23.4 years) who underwent arthroscopic Bankart repair. All anchors were inserted through the anterior portal after establishing a bone hole at the edge of the glenoid articular surface using a drill. Computed tomography images of the scapula were taken 1 month postoperatively and used to create three-dimensional scapula models with Mimics and Magics software. Bone holes in the anterior-inferior (3:00-6:00) position were assigned either to the non-perforated group if they were positioned entirely inside the glenoid bone or to the perforated group if the far cortex of the glenoid was penetrated by the drill. The angle between the glenoid articular surface and the bone hole was measured in the oblique coronal and transverse plane views. The length of the bone hole was also assessed. RESULTS: Of the 85 bone holes investigated, 42 were in the 3:00-6:00 position. Perforation was detected in 16 of these 42 holes (38.2%). The angle in the oblique coronal plane view and the length of the bone hole were significantly larger in the non-perforated group than in the perforated group; however, the angle in the transverse plane view did not significantly differ between the two groups. CONCLUSIONS: Before inserting an implant in the anterior-inferior area, the angle between the drill guide and the glenoid surface in the oblique coronal plane view should be carefully checked to ensure that the length of the hole inside the glenoid bone is adequate.


Assuntos
Artroscopia/métodos , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Escápula/diagnóstico por imagem , Escápula/cirurgia , Luxação do Ombro/diagnóstico por imagem , Luxação do Ombro/cirurgia , Âncoras de Sutura , Tomografia Computadorizada por Raios X , Feminino , Humanos , Imageamento Tridimensional , Masculino , Reprodutibilidade dos Testes , Resultado do Tratamento , Adulto Jovem
18.
Artigo em Inglês | MEDLINE | ID: mdl-38352644

RESUMO

Background: An unstable trochanteric femoral fracture is a serious injury, with a 1-year mortality rate of 5.4% to 24.9%, for which there is currently no standard treatment method. The lag screw insertion site is one of the primary contact areas between the cortical bone and an intramedullary nail. We hypothesized that a posterolateral fracture causes intramedullary nail instability when the posterolateral fracture line interferes with lag screw insertion. The purpose of the present study was to investigate the effect of posterolateral fracture line morphology on intramedullary nail stability by simulating unstable trochanteric femoral fractures with a posterolateral fracture fragment. Methods: Eighteen custom-made synthetic osteoporotic bone samples were used in the present study. Nine samples had a posterolateral fracture line interfering with the lag screw insertion hole (Fracture A), and the other 9 had a fracture line 10 mm away from the hole (Fracture B). Cyclic loading (750 N) was applied to the femoral head 1,500 times. Movement of the end cap attached to the intramedullary nail was recorded. The amplitudes of motion in the coronal plane (coronal swing motion), sagittal plane (sagittal swing motion), and axial plane (total swing motion) were evaluated. The change in the neck-shaft angle was evaluated on photographs that were made before and after the test. Medial cortical displacement was measured before and after the test. Results: Two Fracture-A samples were excluded because the amplitude of sagittal swing motion was too large. The mean values for coronal, sagittal, and total swing motion were 1.13 ± 0.28 mm and 0.51 ± 0.09 mm (p < 0.001), 0.50 ± 0.12 mm and 0.46 ± 0.09 mm (p = 0.46), and 1.24 ± 0.24 mm and 0.69 ± 0.11 mm (p < 0.001) for Fractures A and B, respectively. The mean neck-shaft angle change was -8.29° ± 2.69° and -3.56° ± 2.35° for Fractures A and B, respectively (p = 0.002). The mean displacement of the medial cortex was 0.38 ± 1.12 mm and 0.12 ± 0.37 mm for Fractures A and B, respectively (p = 0.57). Conclusions: This study showed that an unstable trochanteric femoral fracture with a posterolateral fracture line that interferes with the lag screw insertion holes is a risk factor for increased intramedullary nail instability.

19.
Case Rep Orthop ; 2024: 5392926, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38410683

RESUMO

Bite injuries frequently occur on human hands. Human bite injuries to the hand may lead to an infection because of limited soft tissue protection and wound contamination. However, no studies have reported severe bite injuries on hands treated by flaps. We report a case of an 80-year-old woman diagnosed with a major neurocognitive disorder. The patient accidentally had a self-bite injury accompanied with an open metacarpal fracture. Debridement and fixation of the first metacarpal fracture were performed. Afterward, skin necrosis occurred gradually on the dorsum of the hand. Therefore, a reverse posterior interosseous artery (PIA) flap was used, and the postoperative course was uneventful. Given the high risk of infection, human bite injuries, particularly hand bites, should be treated immediately. Delayed treatment for such injuries may lead to extensive soft tissue defects requiring reconstruction with flaps.

20.
Exp Ther Med ; 25(6): 256, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37153894

RESUMO

Hydroxyapatite (HA) augments are used to treat trochanteric femoral fractures. However, the efficacy of HA augmentation has not been fully described in trochanteric femoral fracture surgery. In total, 85 patients were enrolled in the present study; all had trochanteric femoral fractures between January 2016 and October 2020, 45 with HA (HA group) and 40 without HA (N group). The intraoperative lag screw insertion torque was directly measured and the amount of lag screw telescoping with and without HA augmentation after surgery was analyzed. Maximum lag screw insertion torque (max-torque), bone mineral density in the opposite femoral neck (n-BMD), tip apex distance (TAD) of the lag screw, radiographic findings including fracture union, the amounts of lag screw telescoping and occurrence of complications were evaluated. A total of 12 patients were excluded if they were aged under 60 years old, had ipsilateral surgery and disorders in the hip joint, TAD of the lag screw ≥26 mm on postoperative radiographs and had measurement errors. A total of 73 fractures could be analyzed: HA group (n=36) and N group (n=37). Max-torque/n-BMD ratios were higher in the HA group compared with in the N group (7.23±2.71 vs. 5.93±1.91 g/cm2·N·m; P=0.04). The amounts of lag screw telescoping in the HA group were smaller compared with the N group (1.41±2.00 vs. 2.58±2.34; P=0.05). Evaluation of screw insertion torque showed maximum screw insertion torque correlated well with n-BMD in both groups, HA (R=0.57; P<0.01) and N group (R=0.64; P<0.01). No correlation was found between maximum screw insertion torque and TAD in both groups, HA (R=-0.10; P=0.62) and N group (R=0.02; P=0.93). All fractures were radiographically united without any complications. These results support the effectiveness of HA augmentation, indicating higher resistance against rotational instability and reduced lag screw telescoping in trochanteric femoral fracture treatment.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA