RESUMO
Bone marrow-derived mesenchymal stem cells (MSCs), which are capable of differentiating into osteoblasts, are used in effective regenerative therapies. MSCs must be prompted to differentiate into osteoblasts for MSC transplantation to be effective. In this study, osteoblast differentiation markers involved in bone formation were evaluated to investigate the stress resistance of bone marrow-derived rat MSCs to dexamethasone and hypoxia and their ability to differentiate into osteoblasts. MSCs were allowed to differentiate into osteoblasts for 21 days in three different environments (dexamethasone treatment, hypoxic conditions [1% oxygen], or both). Osteoblast differentiation potential was evaluated according to alkaline phosphatase levels and a mineralisation assay. Immunofluorescence staining was used to determine the protein expression of the osteoblast differentiation markers type I collagen and osteopontin. MSCs differentiated into osteoblasts under hypoxic conditions but differentiated more slowly upon treatment with dexamethasone and dexamethasone plus hypoxia relative to the control. MSCs preconditioned with dexamethasone or hypoxia and then allowed to differentiate into osteoblasts under similar conditions differentiated comparably to control MSCs. MSCs that developed resistance to dexamethasone or hypoxia differentiated more quickly into osteoblasts than those that did not. The findings suggest that increasing the resistance of MSCs to stress by preconditioning them via dexamethasone or hypoxia exposure could result in more rapid differentiation into osteoblasts following transplantation.
Assuntos
Diferenciação Celular , Hipóxia Celular , Dexametasona , Células-Tronco Mesenquimais , Osteoblastos , Dexametasona/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Animais , Osteoblastos/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Ratos , Hipóxia Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Células Cultivadas , Fosfatase Alcalina/metabolismo , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Colágeno Tipo I/metabolismo , MasculinoRESUMO
BACKGROUND: Changes in pelvic tilt angle (PTA) and cup orientation have been reported in patients after total hip arthroplasty, but the current literature generally has a brief follow-up period. This study will be the first to report PTA and cup orientation changes in the supine position for a minimum 18 years after total hip arthroplasty (THA) and investigate the factors associated with pelvic tilt and cup orientation changes. METHODS: In this study, 101 patients (120 hips) who underwent THA were retrospectively analyzed. The aims of our study were to evaluate the PTA and cup orientation change over 18 years after THA to assess differential PTA, cup inclination, and anteversion. We also investigated whether factors such as gender, body mass index, and age have any influence on PTA and cup orientation after THA. RESULTS: Patients showed a significant incremental change in PTA pre-operatively, immediately post-operatively, and at final follow-up. Cup orientation increased significantly at the final follow-up compared to the immediate post-operative period. Gender subgroup analysis showed that PTA was significantly greater in females than in males at the final follow-up (p = 0.025). Age subgroup analysis showed that PTA was significantly greater in the over 60 years group than in the other groups. CONCLUSION: Our patients showed significant changes in PTA and cup orientation at a minimum 18 years after surgery, especially in females over 60 years. Female patients over 60 are a risk factor after THA.
Assuntos
Artroplastia de Quadril , Prótese de Quadril , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Artroplastia de Quadril/efeitos adversos , Prótese de Quadril/efeitos adversos , Estudos Retrospectivos , Postura , Pelve/cirurgia , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgiaRESUMO
Adipose-derived stem cell (ADSC) sheets have potential to be effective in various therapies. In this study, we first demonstrated that a cell sheet composed of human ADSCs could be created using a new temperature-responsive culture dish from the DIC Corporation. The dish can cause detachment of adherent cells due to temperature changes, but a few morphological analyses have evaluated the presence or absence of damage on the detached surface of cell sheet. To characterize our ADSC sheet, we tried to observe the surface of ADSC sheets with scanning electron microscope (SEM) using the ionic liquid, which enables the rapid preparation of samples. No damage was found on the surface of the ADSC sheets on the side that had been in contact with the surface of the culture dishes. In addition, when the transcriptomes of the harvested cell sheets were compared with those of monolayer cultures, no up-regulation of cell death related genes were detected. These results propose that the detachment from temperature-responsive culture dish causes no serious damage on the prepared ADSC sheet. It is also suggested that the SEM with ionic liquids is a useful and rapid method for the analysis of ADSC sheets for therapy.
Assuntos
Tecido Adiposo , Células-Tronco , Adipócitos , Humanos , Microscopia Eletrônica de Varredura , TemperaturaRESUMO
Introduction: Recently, the efficacy of mesenchymal stem cells (MSCs) mediated by their tissue repair and anti-inflammatory actions in the prevention and therapy of various disorders has been reported. In this research, our attention was focused specifically on the prevention and therapy of glucocorticoid-induced osteonecrosis. We investigated the stress resistance of MSC against glucocorticoid administration and hypoxic stress, which are factors known to induce osteocytic cell death. Materials and Methods: Mouse bone cells (MLO-Y4) and bone-marrow derived mouse MSCs were exposed to dexamethasone (Dex), hypoxia of 1% oxygen or both in vitro. Mitochondrial membrane potentials were estimated by mitochondria labeling with a cell-permeant probe (Mito tracker red); expression of these apoptosis-inducing molecules, oxidative stress marker (8-hydroxy-2'-deoxyguanosine), caspase-3, -9, and two apoptosis-inhibiting molecules, energy-producing ATP synthase (ATP5A) and X-linked inhibitor of apoptosis protein (XIAP), were analyzed by both immunofluorescence and western blot. Results: With exposure to either dexamethasone or hypoxia, MLO-Y4 showed reduced mitochondrial membrane potential, ATP5A and upregulation of 8-OHdG, cleaved caspases and XIAP. Those changes were significantly enhanced by treatment with dexamethasone plus hypoxia. In MSCs, however, mitochondrial membrane potentials were preserved, while no significant changes in the pro-apoptosis or anti-apoptosis molecules analyzed were found even with exposure to both dexamethasone and hypoxia. No such effects induced by treatment with dexamethasone, hypoxia, or both were demonstrated in MSCs at all. Discussion: In osteocyte cells subjected to the double stresses of glucocorticoid administration and a hypoxic environment osteocytic cell death was mediated via mitochondria. In contrast, MSC subjected to the same stressors showed preservation of mitochondrial function and reduced oxidative stress. Accordingly, even under conditions sufficiently stressful to cause the osteocytic cell death in vivo, it was thought that the function of MSC could be preserved, suggesting that in the case of osteonecrosis preventative and therapeutic strategies incorporating their intraosseous implantation may be promising.
Assuntos
Glucocorticoides/efeitos adversos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteócitos/efeitos dos fármacos , Osteonecrose/terapia , Animais , Apoptose/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/efeitos adversos , Modelos Animais de Doenças , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células-Tronco Mesenquimais/patologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Osteócitos/patologia , Osteonecrose/induzido quimicamente , Osteonecrose/patologiaRESUMO
BACKGROUND: We investigated whether the proximal circumferential porous coating of cementless stems would make implant survival of >20 years possible in young patients. METHODS: Data for patients younger than 50 years with hip dysplasia who had an anatomic stem implanted with a proximal porous coating with hydroxyapatite/tricalcium phosphate were reviewed. Noncircumferential porous (non-C-type) stems were used in 17 hips (13 cases), and circumferential porous (C-type) stems were used in 87 hips (68 cases). Acetabular components with conventional polyethylene were used for all hips. The mean ages at surgery for patients with non-C-type stems and those with C-type stems were 43.3 and 44.7 years, respectively. Stems that had not loosened were retained at the time of acetabular revision. The average duration of follow-up for patients with non-C-type stems was 26.9 years and was 22.3 years for those with C-type stems. RESULTS: Mean survival rates as determined by the Kaplan-Meier method were 74.9% at 20 years and 59.9% at 25 years for non-C-type stems and were 100% at 20 years and 94.0% at 25 years for C-type stems. The survivorship for C-type stems was significantly higher than that for non-C-type stems (P < .01). Focal osteolysis in the shoulder of 37 hips with C-type stems suppressed the spread of osteolysis to the distal femur. CONCLUSION: Anatomic femoral stems with a circumferential porous coating provide excellent durability in patients with hip dysplasia who are 50 years of age or younger. LEVEL OF EVIDENCE: Therapeutic Level IV.
Assuntos
Artroplastia de Quadril , Luxação do Quadril , Prótese de Quadril , Seguimentos , Humanos , Porosidade , Desenho de Prótese , Falha de Prótese , Reoperação , Resultado do TratamentoRESUMO
The main precipitant of glucocorticoid-associated femoral head osteonecrosis is widely accepted to be an ischemic-hypoxic event, with oxidative stress also as an underlying factor. Mitochondrial DNA is more vulnerable to oxidative injury than the nucleus, and mitochondrial transcription factor A (TFAM), which plays roles in its function, preservation, and regulation is being increasingly investigated. In the present study we focused on the impact of TFAM on the relation between the oxidative injury induced by the addition of glucocorticoid to a hypoxic environment and osteocytic cell necrosis. Using cultured osteocytes MLO-Y4 in a 1% hypoxic environment (hypoxia) to which 1µM dexamethasone (Dex) was added (Dex(+)/hypoxia(+)), an immunocytochemical study was conducted using 8-hydroxy-2'-deoxyguanosine (8-OHdG), an index of oxidative stress, and hypoxia inducible factor-1α (HIF-1α), a marker of hypoxia. Next, after adding TFAM siRNA, TFAM knockdown, cultured for 24h, and mitochondrial membrane potential were measured, they were stained with ATP5A which labels adenosine triphosphate (ATP) production. Dex was added to MLO-Y4 to which TFAM had been added, and cultured for 24h in hypoxia. The ratio of dead cells to viable cells was determined and compared. Enhanced expression of 8-OHdG, HIF-1α was found in osteocytes following the addition of glucocorticoid in a hypoxic environment. With TFAM knockdown, as compared to normoxia, mitochondrial function significantly decreased. On the other hand, by adding TFAM, the incidence of osteocytic cell necrosis was significantly decreased as compared with Dex(+)/hypoxia(+). TFAM was confirmed to be important in mitochondrial function and preservation, inhibition of oxidative injury and maintenance of ATP production. Moreover, prevention of mitochondrial injury can best be achieved by decreasing the development of osteocytic cell necrosis.
Assuntos
Proteínas de Ligação a DNA/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/farmacologia , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Fatores de Transcrição/farmacologia , Animais , Western Blotting , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Glucocorticoides/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/fisiologia , Camundongos , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Necrose/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismoRESUMO
BACKGROUND: Low polyethylene wear rate and low incidence of osteolysis have been reported after total hip arthroplasty (THA) using first-generation remelted highly cross-linked polyethylene (HXLPE). However, osteolysis has not been evaluated in long-term studies of these patients (15 years or more). The present study assessed computed tomography (CT) images to determine the incidence of osteolysis associated with HXLPE in THA during at least 15 years of follow-up. METHODS: We evaluated 105 primary THAs in 84 patients (77 women and 7 men). Mean follow-up was 15.9 years (range, 15-18 years). All THAs used a Longevity HXLPE liner and a 26-mm zirconia femoral head. Areas of osteolysis were identified from CT images using 3D and multiplanar reconstruction views. RESULTS: CT 3D multiplanar reconstruction images at 15-year follow-up showed no obvious osteolysis in the acetabulum or femur of any patient. No patients developed cup loosening or liner breakage. CONCLUSION: Our study indicates that first-generation remelted HXLPE liners do not increase the risk of osteolysis during 15-year follow-up and suggests that the wear particles from first-generation remelted HXLPE are less biologically active than those generated by conventional polyethylene devices.
Assuntos
Artroplastia de Quadril , Prótese de Quadril , Osteólise , Artroplastia de Quadril/efeitos adversos , Feminino , Seguimentos , Prótese de Quadril/efeitos adversos , Humanos , Masculino , Osteólise/diagnóstico por imagem , Osteólise/epidemiologia , Osteólise/etiologia , Polietileno , Desenho de Prótese , Falha de Prótese , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Mitochondrial injury has recently been implicated in the pathogenesis of glucocorticoid-induced osteonecrosis. Using cultured osteocytes and a rabbit model, we investigated the possibility that taurine (TAU), which is known to play a role in the preservation of mitochondrial function, might also prevent the development of osteonecrosis. To reduplicate the intraosseous environment seen in glucocorticoid-induced osteonecrosis, dexamethasone (Dex) was added to MLO-Y4 cultured in 1% hypoxia (H-D stress environment). An in vitro study was conducted in which changes in mitochondrial transcription factor A (TFAM), a marker of mitochondrial function, and ATP5A produced by mitochondria, induced by the presence/absence of taurine addition were measured. To confirm the effect of taurine in vivo, 15 Japanese White rabbits were administered methylprednisolone (MP) 20 mg/kg as a single injection into the gluteus muscle (MP+/TAU- group), while for 5 consecutive days from the day of MP administration, taurine 100 mg/kg was administered to 15 animals (MP+/TAU+ group). As a control 15 untreated rabbits were also studied. The rabbits in each of the groups were sacrificed on the 14th day after glucocorticoid administration, and the bilateral femora were harvested. Histopathologically, the incidence of osteonecrosis was quantified immunohistochemically by quantifying TFAM and ATP5A expression. In the rabbits exposed to an H-D stress environment and in MP+/TAU- group, TFAM and ATP5A expression markedly decreased. With addition of taurine in the in vitro and in vivo studies, the expression of TFAM and ATP5A was somewhat decreased as compared with Dex-/hypoxia- or MP-/TAU- group, while improvement was noted as compared with Dex+/hypoxia+ or MP+/TAU- group. In rabbits, the incidence of osteonecrosis was 80% in MP+/TAU- group, in contrast to 20% in the taurine administered group (MP+/TAU+), representing a significant decrease. Since taurine was documented to exert a protective effect on mitochondrial function by inhibiting the mitochondrial dysfunction associated with glucocorticoid administration, we speculated that it might also indirectly help to prevent the development of osteonecrosis in this context. Since taurine is already being used clinically, we considered that its clinical application would also likely be smooth.
Assuntos
Glucocorticoides/efeitos adversos , Mitocôndrias/metabolismo , Osteócitos/metabolismo , Osteonecrose , Taurina/farmacologia , Animais , Linhagem Celular , Glucocorticoides/farmacologia , Camundongos , Mitocôndrias/patologia , Osteócitos/patologia , Osteonecrose/induzido quimicamente , Osteonecrose/metabolismo , Osteonecrose/patologia , Osteonecrose/prevenção & controle , CoelhosRESUMO
The purpose of the role of antioxidant enzymes and mitochondria in the developmental mechanism of steroid-associated osteonecrosis in the femur. In the present study Japanese white rabbits (mean weight 3.5kg) were injected into the gluteus with methylprednisolone (MP) 20mg/kg, and killed after 3 days (MP3 group), 5 days (MP5 group), and 14 days (MP14 group) (n=3 each). As a Control group (C group) Japanese white rabbits not administered MP were used. In experiment 1, the expression of the antioxidant enzymes Superoxide dismutade (SOD) and catalase was compared in liver, kidney, heart, humerus, and femur in C group, and the presence/absence of mitochondria transcription factor A (TFAM) expression was determined by Western blotting (WB) and used to evaluate the number of mitochondria and their function. In experiment 2, the presence/absence of necrosis was determined by immunohistochemistry, while changes in the expression of SOD, catalase, and TFAM in the femur after steroid administration were determined by Western blotting (WB). In experiment 1, intense expression of all of SOD, catalase, and TFAM was found in the liver, kidney, and heart as compared to the humerus and femur. In experiment 2, the expression of all of SOD, catalase, and TFAM in MP3 and MP5 groups was decreased on WB as compared with C group, while in MP14 group a tendency to improvement was seen. Accordingly, steroid-associated mitochondrial injury and redox failure are concluded to be important elements implicated in the pathogenesis of osteonecrosis.
Assuntos
Catalase/genética , Osteonecrose/enzimologia , Esteroides/efeitos adversos , Superóxido Dismutase/genética , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Modelos Animais de Doenças , Regulação Enzimológica da Expressão Gênica , Humanos , Metilprednisolona/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Osteonecrose/induzido quimicamente , Osteonecrose/patologia , Oxirredução/efeitos dos fármacos , Coelhos , Superóxido Dismutase/metabolismoRESUMO
Persistent inflammation is well known to promote the progression of arthropathy. mesenchymal stem cells (MSCs) have been shown to possess anti-inflammatory properties and tissue differentiation potency. Although the experience so far with the intraarticular administration of mesenchymal stem cell (MSC) to induce cartilage regeneration has been disappointing, MSC implantation is now being attempted using various surgical techniques. Meanwhile, prevention of osteoarthritis (OA) progression and pain control remain important components of the treatment of early-stage OA. We prepared a shoulder arthritis model by injecting monoiodoacetate (MIA) into a rat shoulder, and then investigated the intraarticular administration of MSC from the aspects of the cartilage protective effect associated with their anti-inflammatory property and inhibitory effect on central sensitization of pain. When MIA was administered in this rat shoulder arthritis model, anti-Calcitonin Gene Related Peptide (CGRP) was expressed in the joint and C5 spinal dorsal horn. Moreover, expression of A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), a marker of joint cartilage injury, was similarly elevated following MIA administration. When MSC were injected intraarticularly after MIA, the expression of CGRP in the spinal dorsal horn was significantly deceased, indicating suppression of the central sensitization of pain. The expression of ADAMTS 5 in joint cartilage was also significantly inhibited by MSC administration. In contrast, a significant increase in the expression of TNF-α stimulated gene/protein 6 (TSG-6), an anti-inflammatory and cartilage protective factor shown to be produced and secreted by MSC intraarticularly, was found to extend to the cartilage tissue following MSC administration. In this way, the intraarticular injection of MSC inhibited the central sensitization of pain and increased the expression of the anti-inflammatory and cartilage protective factor TSG-6. As the least invasive conservative strategies possible are desirable in the actual clinical setting, the intraarticular administration of MSC, which appears to be effective for the treatment of pain and cartilage protection in early-stage arthritis, may achieve these aims.
Assuntos
Transplante de Células-Tronco Mesenquimais , Osteoartrite/patologia , Proteína ADAMTS5/genética , Proteína ADAMTS5/metabolismo , Animais , Peptídeo Relacionado com Gene de Calcitonina/genética , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Cartilagem Articular/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Injeções Intra-Articulares , Ácido Iodoacético/toxicidade , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Microscopia de Fluorescência , Osteoartrite/induzido quimicamente , Osteoartrite/terapia , Dor/patologia , Dor/prevenção & controle , Ratos , Ratos Sprague-Dawley , Corno Dorsal da Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal/patologiaRESUMO
We investigated the role of programmed necrosis (necroptosis), a newly recognized form of cell necrosis that has been implicated in the development of steroid-induced osteonecrosis. We used an osteonecrosis model in which 30 Japanese white rabbits each weighing 3.5kg were injected once with methylprednisolone at 20 mg/kg body weight into the right gluteal muscle. Ten animals killed 14 days thereafter were designated as S14d groups, while another 10 animals injected with necroptosis, a specific inhibitor of necrostatin-1 i.v. at 1.65mg/kg on the same day as the steroid were also killed on the 14th day and designated as SN14d group. As a control, 10 animals injected only with physiological saline were studied as N group. After the animals were sacrificed the bilateral femoral bone was examined histopathologically and the presence of osteonecrosis determined. Furthermore, animals subjected to the same treatment and killed on the 3rd day after drug administration were set up as S3d group and SN3d group, and Western blotting of Receptor-interacting protein ( RIP ) 1 and RIP3 in femoral bone performed. The osteonecrosis rate was 70% in S14d group, and 0% in both N and SN groups. In 2 of 10 animals in SN group fatty marrow was found. On Western blotting significantly increased expression of both RIP1 and RIP3 was noted in S3d group, confirming that Nec-1 was suppressed. Necroptosis mediated by RIP1 and RIP3 expression was thought to be implicated in the development of steroid-induced osteonecrosis. Also, by suppressing expression of RIP1 and 3 with the administration of Nec-1 the osteonecrosis rate was significantly decreased. These results suggest that necroptosis may have potential as a novel target for both elucidating the mechanisms underlying steroid-induced osteonecrosis and establishing more effective prophylactic countermeasures.
Assuntos
Necrose/metabolismo , Necrose/fisiopatologia , Osteonecrose/metabolismo , Osteonecrose/fisiopatologia , Esteroides/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Proteínas Serina-Treonina Quinases/metabolismo , Coelhos , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismoRESUMO
BACKGROUND: Glucocorticoid-associated osteonecrosis is an intractable condition, making the establishment of preventative strategies of particular importance. Recently various studies using mesenchymal stem cells (MSC) have been conducted. Using a rabbit glucocorticoid-associated osteonecrosis model we administered green fluorescent protein (GFP)-labeled MSC intravenously to investigate their effect on osteonecrosis. METHODS: A rabbit osteonecrosis model in which methylprednisolone (MP) 20 mg/kg was injected into the gluteus of a Japanese white rabbit was used. Simultaneously with MP, MSC labeled with GFP (GFP-labeled MSC) were injected intravenously. Fourteen days later the animals were killed (MSC(+)/MP(+)/14d), femurs were extracted, and the prevalence of osteonecrosis was determined histopathologically. Also, animals were killed 3 days after simultaneous administration of GFP-labeled MSC and MP (MSC(+)/MP(+)/3d), and western blotting (WB) for GFP was performed of the femur, liver, kidney, lung, blood vessel, and vertebra, in addition to immunohistochemical study of femur. As a control for the histopathological study, animals were killed 14 days after MP administration and intravenous vehicle injection (MSC(-)/MP(+)/14d). For WB, animals were killed 3 days after intravenous GFP-labeled MSC administration and vehicle injection into the gluteus (MSC(+)/MP(-)/3d). RESULTS: In MSC(-)/MP(+)/14d osteonecrosis was found in 7 of 10 rabbits (70%), while in MSC(+)/MP(+)/14d, partial bone marrow necrosis was found in only 1 rabbit (12.5%); osteonecrosis was not found in 7 of 8 rabbits (p < 0.05). WB showed expression of GFP in the femur, not in the liver, kidney, lung, blood vessel, or vertebra, of MSC(+)/MP(+)/3d; expression of GFP-labeled MSC was absent in the femur of MSC(+)/MP(-)/3d. In the immunohistochemical study of MSC(+)/MP(+)/3d, homing of GFP-labeled MSC was noted perivascularly in the femur, but not in MSC(+)/MP(-)/3d. CONCLUSIONS: With transvenous MSC administration a significant prophylactic effect against glucocorticoid-associated osteonecrosis was found. Direct administration of MSC to the site of tissue injury requires highly invasive surgery. In contrast, as shown here the simple and hardly invasive intravenous administration of MSC may succeed in preventing osteonecrosis.
Assuntos
Necrose da Cabeça do Fêmur/prevenção & controle , Glucocorticoides/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Modelos Animais de Doenças , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/patologia , Humanos , Injeções Intravenosas , Metilprednisolona/efeitos adversos , CoelhosRESUMO
INTRODUCTION: Rotational acetabular osteotomy (RAO) has been used successfully in patients with developmental dysplasia of the hip (DDH). However, some patients are forced to undergo total hip arthroplasty (THA) because of the progression of osteoarthritis. We evaluated the effect of previous RAO on the outcome of THA performed for degenerative arthritis secondary to DDH, comparing outcomes for patients with THA and prior RAO versus outcomes for patients with THA and no prior RAO. MATERIALS AND METHODS: At an average follow-up point of 8.2 years (range 7-11 years), we compared outcomes in dysplastic hips for 22 hips (group R) in patients who underwent THA after successful RAO with outcomes for a well-matched control group of 30 hips in patients who underwent primary THA (group C) during the same period. RESULTS: Both groups had similar midterm results. No acetabular or femoral components exhibited loosening or revision in either group. Harris hip scores (HHSs) at the most recent follow-up had not been compromised by RAO, and there were no significant differences in intraoperative blood loss and operative time between the two groups. Although there was a tendency toward superolateral placement of the acetabular component in group R, there were no significant differences in the mean steady-state linear and volumetric wear rates between the two groups. There were no infections, dislocations, intraoperative fractures, damaged nerves, or deep vein thromboses in either group. CONCLUSIONS: Our midterm results demonstrated that RAO does not lead to higher revision rates, compromised HHSs, or shortened survivorship in eventual THA for DDH.
Assuntos
Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Luxação Congênita de Quadril/cirurgia , Osteoartrite do Quadril/cirurgia , Osteotomia/métodos , Acetábulo/diagnóstico por imagem , Idoso , Feminino , Seguimentos , Luxação Congênita de Quadril/complicações , Luxação Congênita de Quadril/diagnóstico por imagem , Humanos , Luxações Articulares/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/etiologia , Radiografia , Reoperação , Estudos Retrospectivos , Rotação , Resultado do TratamentoRESUMO
Osteonecrosis is a major glucocorticoid-induced complication in the orthopedics field. Despite the extensive researches, mechanisms underlining the glucocorticoid-induced osteonecrosis are largely unknown. Here, we first provide the evidence that a combined treatment of cultured osteocytic cells with glucocorticoid and hypoxia caused necrotic cell death, which is assumed to occur in the acute bone injuries induced by glucocorticoids. We cultured MLO-Y4 murine osteocytic cells under hypoxia in the presence or absence of Dexamethasone (Dex) and examined the rates of apoptotic and necrotic cell death. Dex or hypoxia alone increased apoptotic cells, but not necrotic cells. The combination of Dex and hypoxia dramatically increased osteocytic cell death, notably necrotic cell death. The expression of Dickkopf-1 (Dkk-1), an inhibitor of Wnt/ß-catenin signal, was scarcely expressed in the control and hypoxic cells, but a dramatic increase of the Dkk-1 expression was detected in Dex-treated cells. siRNA-mediated knockdown of Dkk-1 in Dex and hypoxia-treated osteocytic cells showed the significant decreases in both apoptotic and necrotic cells. The results indicated that the combination of Dkk-1 overexpression by Dex and hypoxia causes the necrotic osteocytic cell death. The results also indicated that blocking of Dkk-1 can protect bone cells from glucocorticoid and hypoxia-induced cell injury.
Assuntos
Hipóxia/patologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Necrose/metabolismo , Osteócitos/metabolismo , Osteócitos/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Linhagem Celular , Dexametasona/efeitos adversos , Glucocorticoides/metabolismo , Hipóxia/induzido quimicamente , Hipóxia/metabolismo , Camundongos , Necrose/induzido quimicamente , Osteócitos/efeitos dos fármacos , RNA Interferente Pequeno/metabolismoRESUMO
INTRODUCTION: Femoral component revisions with extensively porous-coated stems have shown promising clinical results, although there are still concerns over stress-shielding. MATERIALS AND METHODS: We retrospectively reviewed data for 18 patients undergoing femoral component revisions with extensively porous-coated stems with high stiffness. The average length of follow-up was 10 years (range 6-13.7 years). RESULTS: Radiographic evidence of a bone-ingrown stem was present in 94 % of the hips, and stable fibrous fixation was present in only one hip, but no hips were considered unstable. There was mild stress-shielding in 15 hips, moderate stress-shielding in one hip, and severe stress-shielding in two hips. In one of the latter two hips, stress-shielding was progressive even 8 years after revision surgery. In 12 (92 %) of the 13 hips in which bypass fixation for diaphyseal cortical defects was used, there was good remodeling. CONCLUSIONS: We suggest that femoral component revision using extensive porous-coated stems is a useful option that may allow for healing of diaphyseal cortical defects.
Assuntos
Artroplastia de Quadril/efeitos adversos , Doenças Ósseas/cirurgia , Remodelação Óssea/fisiologia , Diáfises/cirurgia , Fêmur/cirurgia , Adulto , Idoso , Doenças Ósseas/fisiopatologia , Materiais Revestidos Biocompatíveis , Feminino , Hemiartroplastia/efeitos adversos , Prótese de Quadril/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas Periprotéticas/fisiopatologia , Fraturas Periprotéticas/cirurgia , Porosidade , Desenho de Prótese , Falha de Prótese/efeitos adversos , Reoperação , Estudos RetrospectivosRESUMO
Zirconia femoral heads were introduced for total hip arthroplasty (THA) with the expectation of lower polyethylene (PE) wear and better clinical results. Because several studies reported poor survivorship of yttria-stabilized zirconia-PE THA, we investigated a new-generation yttria-stabilized zirconia head (diameter, 26 mm) manufactured by NGK Spark Plug. We retrieved six zirconia heads at revision THA after they had been in place for a mean of 8.6 years and measured their surface roughness and mean monoclinic content. Although their mean monoclinic content was higher than that of the unused head, surface roughness in the implanted heads was as low as that of the unused head, indicating that wear reduction may be possible with the selection of a suitable zirconia femoral head.
Assuntos
Artroplastia de Quadril/instrumentação , Prótese de Quadril , Ítrio , Zircônio , Idoso , Idoso de 80 Anos ou mais , Remoção de Dispositivo , Dureza , Humanos , Teste de Materiais , Pessoa de Meia-Idade , Polietileno , Desenho de Prótese , Reoperação , Propriedades de SuperfícieRESUMO
BACKGROUND Septic arthritis of the shoulder is a rare and challenging condition to treat. Typically, arthroscopic debridement is the common approach. Specifically, septic arthritis of the shoulder caused by methicillin-resistant bacteria is extremely difficult to cure due to persistent infection and limited antibiotic options. However, recent studies have demonstrated that continuous local antibiotic perfusion (CLAP) can provide favorable results for bone and soft tissue infections. By administering the antibiotics required to suppress the biofilm, CLAP can effectively treat the infection while sparing the tissue. CASE REPORT A 46-year-old woman undergoing long-term hemodialysis treatment for congenital anomalies of the kidney and urinary tract experienced severe pain in the left shoulder joint during glucocorticoid treatment for amyloid arthritis of the right shoulder. Despite the absence of fever, significant swelling and fluid accumulation were observed in the left shoulder joint, leading to the performance of a puncture. A bacterial examination of the puncture fluid detected methicillin-resistant coagulase-negative Staphylococcus epidermidis (MRCNS). In this report, we present a case in which CLAP was administered for septic arthritis of the shoulder caused by methicillin-resistant bacteria. After irrigation debridement, the patient received intravenous antibiotics and CLAP. Following the initiation of treatment, the dosage of antibiotics was adjusted while performing therapeutic drug monitoring. An early improvement in the inflammatory response and sedation of the infection was observed, with no relapse after 2 years. CONCLUSIONS Septic arthritis can lead to serious functional impairment if left untreated. CLAP is a promising option for managing septic arthritis of the shoulder.
Assuntos
Antibacterianos , Artrite Infecciosa , Articulação do Ombro , Infecções Estafilocócicas , Humanos , Feminino , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/microbiologia , Artrite Infecciosa/terapia , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Articulação do Ombro/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Desbridamento , Seguimentos , Staphylococcus epidermidis/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Resistência a MeticilinaRESUMO
Introduction: Administration of adipose-derived stem cells (ADSCs) into the joint cavity has been shown to alleviate the symptoms of knee osteoarthritis (OA) by releasing exosomes and anti-inflammatory cytokines. However, the therapeutic effect of these cells is limited by their rapid disappearance after administration. Thus, it is necessary to prolong cell survival in the joint cavity. This study aimed to investigate the potential application of ADSCs adhered to atelocollagen microspheres (AMSs) for cell therapy of knee OA. Methods: ADSCs were cultured for 2, 4, and 7 days in AMS suspension or adherent culture dishes. The supernatants were analyzed for IL-10 and exosome secretion via enzyme-linked immunosorbent assay and Nanosight. The effect of AMS was compared with that of adherent-cultured ADSCs (2D-cultured ADSCs) using transcriptome analysis. Moreover, the solubility of AMS and viability of ADSCs were evaluated using synovial fluid (SF) from patients with knee OA. Results: Compared with 2D-cultured ADSCs, AMS-cultured ADSCs exhibited a significant increase in secretion of exosomes and IL-10, and the expression of several genes involved in extracellular matrix and immune regulation were altered. Furthermore, when AMS-cultured ADSCs were cultured in SF from knee OA patients to mimic the intra-articular environment, the SF dissolved the AMSs and released viable ADSCs. In addition, AMS-cultured ADSCs showed significantly higher long-term cell viability than 2D-cultured ADSCs. Conclusion: Increased survival of AMS-adhered ADSCs was observed in the intra-articular environment, and AMSs were found to gradually dissipate. These results suggest that AMS-adhered ADSCs are promising source for cell therapy of knee OA.
RESUMO
Anatomic femoral components are optimized for primary osteoarthritis, and few long-term results for their use are available for developmental dysplasia of the hip (DDH). We reviewed 135 uncemented total hip arthroplasties in which an anatomic femoral component was used in 106 patients with DDH, excluding femurs with neck-shaft angles of >160° and femurs with anteversion of >50°. The mean age of patients at surgery was 49.4 years (range, 33-66 years), and the mean duration of follow-up was 13.5 years (range, 10-18 years). No osteoporotic femurs were included in our study group. Despite 18 acetabular revisions, no femoral component was removed for any reason. No femoral loosening was seen at the final follow-up examination. An anatomic femoral component with circumferential porous coating can produce good clinical and radiologic findings in young patients with good bone quality who have DDH without excessive femoral deformity.
Assuntos
Artroplastia de Quadril , Luxação Congênita de Quadril/cirurgia , Prótese de Quadril , Adulto , Feminino , Seguimentos , Luxação Congênita de Quadril/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Osteólise/diagnóstico por imagem , Osteólise/etiologia , Desenho de Prótese , Radiografia , Estudos RetrospectivosRESUMO
We previously reported the results of wear comparison at a minimum of 5 years between highly cross-linked polyethylene (HXLPE) and conventional polyethylene (PE) against a zirconia femoral head. We now report the mean wear at 10 years for 52 patients (56 hips) of the original cohort of 61 patients (65 hips) who had undergone primary total hip arthroplasty at our hospital between November 1999 and August 2000. The mean steady-state linear wear rate of HXLPE was 0.045 mm/y, compared with 0.080 mm/y for conventional PE (P=.0003). The incidence of osteolysis was 25% in the conventional PE group compared with 0% in the HXLPE group. Our study demonstrated that the steady-state wear rate for HXLPE remains significantly lower than that for conventional PE against a zirconia femoral head at a mean of 10 years after implantation.