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PURPOSE: This study aimed to consolidate the evidence regarding the prognostic influence of sarcopenia in degenerative lumbar spine surgeries. METHODS: A literature search of public databases was conducted up to Nov 15, 2023 using combinations of the key words "sarcopenia" and "lumbar spine surgery". Eligible studies were those that focused on adults undergoing decompression or fusion surgery for degenerative lumbar spine diseases, and compared the outcomes between patients with and without preoperative sarcopenia. Primary outcomes were change in ODI and back and leg pain VAS pain scores. Secondary outcomes were changes in Eq. 5D, JOA, SFHS-p scores, and LOS. RESULTS: Ultimately, nine retrospective studies with a total of 993 patients were included. Sarcopenic patients exhibited significantly worse functional improvement as assessed by ODI compared to non-sarcopenic patients (pooled standardized mean difference [pSMD] = 0.53, 95% confidence interval [CI]: 0.17-0.90). Back pain (pSMD = 0.31, 95% CI:0.15-0.47) and leg pain (pSMD = 0.21, 95% CI:0.02 - 0.39) improvement were also less in sarcopenic patients. Non-sarcopenic patients had greater improvements in Eq. 5D (pSMD = 0.25) and SFHS-p (pSMD = 0.39), and shorter LOS (pSMD = 0.62). CONCLUSIONS: As compared to patients without sarcopenia, those with sarcopenia undergoing lumbar spine surgery for degenerative diseases have lower improvements in functional ability, quality of life, physical health, pain relief and extended hospitalization compared to those without sarcopenia.
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Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Extracellular vesicles called exosomes are primarily used as mediators of intercellular signal transmission to control tumor metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with exosome generation in chondrosarcoma motility remains undetermined. Our results found that overexpressing visfatin augments the production of exosomes from chondrosarcoma cells. Visfatin-treated chondrosarcoma exosomes educate macrophage polarization towards the M2 but not M1 phenotype. Interestingly, M2 macrophages polarized by exosomes return to chondrosarcoma cells to facilitate cell motility. According to these findings, chondrosarcoma cells emit more exosomes when treated with visfatin. The stimulation of exosome generation by visfatin polarizes M2 macrophages and enhances the motility of chondrosarcoma.
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Movimiento Celular , Condrosarcoma , Exosomas , Macrófagos , Nicotinamida Fosforribosiltransferasa , Condrosarcoma/patología , Condrosarcoma/metabolismo , Exosomas/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Humanos , Nicotinamida Fosforribosiltransferasa/metabolismo , Movimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Citocinas/metabolismoRESUMEN
Osteoarthritis (OA) is a degenerative joint disease primarily affecting the elderly. It is characterized by the progressive decline of joint cartilage and alterations in the underlying bone. Several probiotic strains have exhibited immunomodulatory and anti-inflammatory properties. Here, we examined the functions of live and dead Clostridium butyricum GKB7 (GKB7-L and GKB7-D) in a preclinical anterior cruciate ligament transection (ACLT)-enhanced OA procedure. Oral administration of GKB7-L and GKB7-D ameliorated ACLT-induced bone pain as assessed by weight-bearing behavioral testing but did not affect body weight. Micro-computed tomography (CT) results showed that GKB7-L and GKB7-D diminished ACLT-induced bone destruction and loss. GKB7-L and GKB7-D-enriched therapies also reduced ACLT-induced production of the pro-inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, as well as the chondrolytic factor matrix metalloproteinase (MMP)-3, leading to inhibition of aggrecan and collagen type II degradation and thereby blocking cartilage breakdown. We therefore suggest that oral supplementation with GKB7-L or GKB7-D can be beneficial in the prevention and treatment of OA.
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Osteoporosis is a common bone disease in aging populations, particularly in postmenopausal women. Anti-resorptive and anabolic drugs have been applied to prevent and cure osteoporosis and are linked with a variety of adverse effects. Antrodia cinnamomea extracts (ACE) are highly renowned for their anticancer, antioxidative, and anti-inflammatory properties. However, whether ACE-enriched anti-osteoporosis functions are largely unknown. In a preclinical animal model, we found that ovariectomy significantly decreased bone volume in the ovariectomized (OVX) rats. Administration of ACE antagonized OVX-induced bone loss. In addition, ACE reversed OVX-reduced biomechanical properties. The serum osteoclast marker also showed improvement in the ACE-treated group. In the cellular model, it was indicated that ACE inhibits RANKL-induced osteoclast formation. Taken together, ACE seems to be a hopeful candidate for the development of novel anti-osteoporosis treatment.
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Osteoclastos , Osteoporosis , Ovariectomía , Ratas Sprague-Dawley , Animales , Femenino , Osteoclastos/efectos de los fármacos , Osteoporosis/prevención & control , Osteoporosis/tratamiento farmacológico , Osteoporosis/patología , Ratones , Ratas , Células RAW 264.7 , Polyporales/química , Resorción Ósea/prevención & control , Resorción Ósea/tratamiento farmacológico , Ligando RANKRESUMEN
Rheumatoid arthritis (RA) is a well-known autoimmune disorder related with joint pain, joint swelling, cartilage and bone degradation as well as deformity. Fibroblast growth factor 23 (FGF23) is an endocrine factor of the FGF family primarily produced by osteocytes and osteoblasts, involves an essential effect in pathogenesis of RA. IL-1ß is a vital proinflammatory factor in the development of RA. However, the role of FGF23 on IL-1ß synthesis in RA has not been fully explored. Our analysis of database revealed higher levels of FGF23 and IL-1ß in RA samples compared with healthy controls. High-throughput screening demonstrated that IL-1ß is a potential candidate factor after FGF23 treatment in RA synovial fibroblasts (RASFs). FGF23 concentration dependently promotes IL-1ß synthesis in RASFs. FGF23 enhances IL-1ß expression by activating the PI3K, Akt, and NF-κB pathways. Our findings support the notion that FGF23 is a promising target in the remedy of RA.
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Artritis Reumatoide , Factor-23 de Crecimiento de Fibroblastos , Fibroblastos , Interleucina-1beta , Transducción de Señal , Femenino , Humanos , Masculino , Artritis Reumatoide/metabolismo , Células Cultivadas , Factores de Crecimiento de Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Interleucina-1beta/metabolismo , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/metabolismoRESUMEN
Background and Objectives: Adolescent idiopathic scoliosis (AIS) is a prevalent three-dimensional spinal disorder, with a multifactorial pathogenesis, including genetics and environmental aspects. Treatment options include non-surgical and surgical treatment. Surgical interventions demonstrate positive outcomes in terms of deformity correction, pain relief, and improvements of the cardiac and pulmonary function. Surgical complications, including excessive blood loss and neurologic deficits, are reported in 2.27-12% of cases. Navigation-assisted techniques, such as the O-arm system, have been a recent focus with enhanced precision. This study aims to evaluate the results and complications of one-stage posterior instrumentation fusion in AIS patients assisted by O-arm navigation. Materials and Methods: This retrospective study assesses 55 patients with AIS (12-28 years) who underwent one-stage posterior instrumentation correction supported by O-arm navigation from June 2016 to August 2023. We examined radiological surgical outcomes (initial correction rate, loss of correction rate, last follow-up correction rate) and complications as major outcomes. The characteristics of the patients, intraoperative blood loss, operation time, number of fusion levels, and screw density were documented. Results: Of 73 patients, 55 met the inclusion criteria. The average age was 16.67 years, with a predominance of females (78.2%). The surgical outcomes demonstrated substantial initial correction (58.88%) and sustained positive radiological impact at the last follow-up (56.56%). Perioperative complications, including major and minor, occurred in 18.18% of the cases. Two patients experienced a major complication. Blood loss (509.46 mL) and operation time (402.13 min) were comparable to the literature ranges. Trend analysis indicated improvements in operation time and blood loss over the study period. Conclusions: O-arm navigation-assisted one-stage posterior instrumentation proves reliable for AIS corrective surgery, achieving significant and sustained positive radiological outcomes, lower correction loss, reduced intraoperative blood loss, and absence of implant-related complications. Despite the challenges, our study demonstrates the efficacy and maturation of this surgical approach.
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Cifosis , Tornillos Pediculares , Escoliosis , Fusión Vertebral , Cirugía Asistida por Computador , Femenino , Humanos , Adolescente , Masculino , Escoliosis/cirugía , Escoliosis/complicaciones , Tornillos Pediculares/efectos adversos , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Fusión Vertebral/métodos , Imagenología Tridimensional , Tomografía Computarizada por Rayos X/métodos , Cifosis/cirugía , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Vértebras TorácicasRESUMEN
Background: Spinal fusion is a common surgery, in which vertebrae are fused to restore spinal stability and eliminate pain during movement. The use of an interbody cage facilitates spinal fusion. However, complete cage migration into the dura matter rarely occurs and can be challenging to manage. Case Presentation: A 44-year-old man presented at our spine center with a history of incomplete paraplegia and cauda equina syndrome that had lasted for 2 years and 4 months. This condition developed after he underwent six lumbar spine surgeries to address lower back pain and right-sided sciatica. A structural allograft kidney-shaped cage was found completely within the dura at the level of the L3 vertebra. Durotomy, cage retrieval, and pedicle screw fixation from the L2 to L4 vertebrae were performed. Numbness in both lower limbs markedly decreased within several days of the operation. After four months following the progressive physical therapy, the patient could partially control both urination and defecation. Five months postoperatively, he could stand with slight assistance. Conclusions: Complete intradural cage migration is a rare and serious complication. To the best of our knowledge, this is the first reported case with such a condition in the literature. Even if treatment is delayed, surgical intervention may salvage the remaining neurologic function and may even lead to partial recovery.
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Tornillos Pediculares , Fusión Vertebral , Masculino , Humanos , Adulto , Fusión Vertebral/efectos adversos , Vértebras Lumbares/cirugía , Procedimientos NeuroquirúrgicosRESUMEN
Osteoarthritis (OA) is a progressive degenerative joint disorder characterized by synovial inflammation. Interleukin-6 (IL-6) is a key proinflammatory cytokine in OA progression. Particulate matter 2.5 (PM2.5) exposure increases the risk of different diseases, including OA. Up until now, no studies have described any association between PM2.5 and IL-6 expression in human OA synovial fibroblasts (OASFs). Here, our data show that PM2.5 concentration- and time-dependently promoted IL-6 synthesis in human OASFs. We also found that reactive oxygen species (ROS) generation potentiated the effects of PM2.5 on IL-6 production. ASK1, ERK, p38, and JNK inhibitors reduced PM2.5-induced increases of IL-6 expression. Treatment of OASFs with PM2.5 promoted phosphorylation of these signaling cascades. We also found that PM2.5 enhanced c-Jun phosphorylation and its translocation into the nucleus. Thus, PM2.5 increases IL-6 production in human OASFs via the ROS, ASK1, ERK, p38, JNK, and AP-1 signaling pathways. Our evidence links PM2.5 with OA progression.
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Fibroblastos/patología , Interleucina-6/biosíntesis , MAP Quinasa Quinasa Quinasa 5/metabolismo , Osteoartritis/enzimología , Osteoartritis/patología , Material Particulado/toxicidad , Membrana Sinovial/patología , Activación Enzimática/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Modelos Biológicos , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción AP-1/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Chondrosarcoma is a malignant bone tumor that is characterized by high metastatic potential and marked resistance to radiation and chemotherapy. The knowledge that adipokines facilitate the initiation, progression, metastasis, and treatment resistance of various tumors has driven several in vitro and in vivo investigations into the effects of adipokines resistin, leptin, and adiponectin upon the development and progression of chondrosarcomas. Another adipokine, visfatin, is known to regulate tumor progression and metastasis, although how this molecule may affect chondrosarcoma metastasis is unclear. Here, we found that visfatin facilitated cellular migration via matrix metalloproteinase-2 (MMP-2) production in human chondrosarcoma cells and overexpression of visfatin enhanced lung metastasis in a mouse model of chondrosarcoma. Visfatin-induced stimulation of MMP-2 synthesis and activation of the AP-1 transcription factor facilitated chondrosarcoma cell migration via the ERK, p38, and JNK signaling pathways. This evidence suggests that visfatin is worth targeting in the treatment of metastatic chondrosarcoma.
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Neoplasias Óseas/patología , Condrosarcoma/patología , Citocinas/fisiología , Metaloproteinasa 2 de la Matriz/genética , Nicotinamida Fosforribosiltransferasa/fisiología , Animales , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Condrosarcoma/genética , Condrosarcoma/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Sistema de Señalización de MAP Quinasas/genética , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia , Factor de Transcripción AP-1/metabolismo , Factor de Transcripción AP-1/fisiología , Células Tumorales CultivadasRESUMEN
BACKGROUND: The aim of this study is to introduce a new method of percutaneous endoscopic decompression under 3D real-time image-guided navigation for spinal stenosis in degenerative kyphoscoliosis patients without instability or those who with multiple comorbidities. Decompression alone using endoscope for kyphoscoliosis patient is technical demanding and may result in unnecessary bone destruction leading to further instability. The O-arm/StealthStation system is popular for its ability to provide automated registration with intraoperative, postpositioning computed tomography (CT) which results in superior accuracy in spine surgery. METHODS: In this study, we presented four cases. All patients were over seventy years old female with variable degrees of kyphoscoliosis and multiple comorbidities who could not endure major spine fusion surgery. Percutaneous endoscopic unilateral laminotomy and bilateral decompression under 3D real-time image-guided navigation were successfully performed. Patients' demographics, image study parameters, and outcome measurements including pre- and post-operative serial Visual analog scale (VAS), and Oswestry Disability Index (ODI) were well documented. The follow-up time was 1 year. RESULTS: Pre- and post-operative MRI showed average dural sac cross sectional area (DSCSA) improved from 81.62 (range 67.34-89.07) to 153.27 (range 127.96-189.73). Preoperative neurological symptoms including radicular leg pain improved postoperatively. The mean ODI (%) were 85 (range 82.5-90) at initial visit, 35.875 (range 25-51) at 1 month post-operatively, 26.875 (range 22.5-35) at 6 months post-operatively and 22.5 (range 17.5-30) at 12 months post-operatively (p < 0.05). The mean VAS score were 9 (range 8-10) at initial visit, 2.25 (range 2-3) at 1 month post-operatively, 1.75 (range 1-2) at 6 months post-operatively and 0.25 (range 0-1) at 12 months post-operatively (p < 0.05). There was no surgery-related complication. CONCLUSIONS: To the best of our knowledge, this is the first preliminary study of percutaneous endoscopic laminotomy under O-arm navigation with successful outcomes. The innovative technique may serve as a promising solution in treating spinal stenosis patients with lumbar kyphoscoliosis and multiple comorbidities.
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Estenosis Espinal , Cirugía Asistida por Computador , Anciano , Descompresión Quirúrgica , Femenino , Humanos , Imagenología Tridimensional , Laminectomía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Estenosis Espinal/complicaciones , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Background and Objectives: The proximity of the popliteal vessels in the distal femur may increase the risk of iatrogenic vascular injury during cerclage wiring. In this study, the closest location and distance of the popliteal vessels to the femur was examined using magnetic resonance imaging (MRI). The associations between anthropometric factors and the distance that would guide the placement of wires safely during surgery were also identified. Materials and Methods: We reviewed adult knee magnetic resonance images and recorded: (1) the relation and the shortest horizontal distance (d-H) from the femoral cortex to the popliteal vessels in axial images and (2) the vertical distance (d-V) from the adductor tubercle to the axial level of the d-H values in coronal images. The effects of anthropometric factors (sex, age, body height, body weight, body mass index, thigh circumference, femoral length and femoral width) on these distances were analysed. Results: Analysis of 206 knee magnetic resonance images revealed that the closet locations of popliteal vessels were at the posteromedial aspect of the femur. The d-H and d-V were 7.38 ± 3.22 mm and 57.01 ± 11.14 mm, respectively, and were both shorter in women than in men (p < 0.001). Multivariate analysis identified thigh circumference and femoral length as the most influential factors for the d-H and d-V, respectively (p < 0.001). Linear regression demonstrated a strong positive linear correlation between the thigh circumference and the d-H and between the femoral length and the d-V (Pearson's r = 0.891 and 0.806, respectively (p < 0.001)). Conclusions: The closet location and distance of the popliteal vessels to the femur provide useful information for wire placement during distal femoral fracture surgery while minimising the risk of vascular injury. Given that patients with a smaller thigh circumference and a shorter femoral length are more likely to have a smaller d-H and a shorter d-V, respectively, cautious measures should be taken in such cases.
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Fracturas del Fémur , Adulto , Hilos Ortopédicos , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Fémur/diagnóstico por imagen , Fémur/cirugía , Fijación Interna de Fracturas , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
PURPOSE: The diagnosis of painful cemented vertebrae resulting from failed PV is not clearly defined in literature. This report evaluates the effectiveness of modified dynamic radiographs in diagnosing painful cemented vertebrae resulting from failed PV. METHODS: From January 2011 to June 2015, 345 patients with a total of 399 VCFs underwent PV at our institution. Among the 345 patients, 27 patients underwent repeated PV at the cemented vertebrae because of persisting or recurrent pain after vertebroplasty. The prevertebroplasty examinations included routine radiographs, modified dynamic radiographs, and MRI. Kyphotic angles and the anterior vertebral body height (AVBH) were measured. The image findings in routine radiographs, modified dynamic radiographs, and MRI were compared. Finally, a visual analog scale was used to measure the outcome. RESULTS: The patients ranged in age from 67 to 90 years. MRI revealed a moderate amount of fluid (definite diagnosis of refracture) in the cemented vertebrae in seven patients, bone edema without fluid in nine patients, and bone edema with minimal fluid in ten patients. The rate of diagnosis of painful cemented vertebrae according to MRI was 27% (7/26). The difference in the kyphotic angle between sitting and supine cross-table lateral radiographs was -9.36° ± 5.20° (P < 0.001). The difference in AVBH was 8.08 ± 3.21 mm (P < 0.001). All 27 patients were confirmed to have dynamic mobility according to the modified dynamic radiographs. CONCLUSIONS: When the diagnosis of painful cemented vertebrae is questionable, modified dynamic radiographs can help diagnose painful cemented vertebrae resulting from failed PV.
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Fracturas por Compresión/cirugía , Fracturas Osteoporóticas/cirugía , Dolor Postoperatorio/diagnóstico por imagen , Fracturas de la Columna Vertebral/cirugía , Vertebroplastia , Anciano , Anciano de 80 o más Años , Cementos para Huesos , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Dimensión del Dolor , Radiografía , Estudios Retrospectivos , Insuficiencia del Tratamiento , Vertebroplastia/instrumentaciónRESUMEN
Chondrosarcoma is the second most frequently occurring type of bone malignancy characterized by distant metastatic propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumour lymphangiogenesis and lymphatic metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. In recent years, adiponectin has also been indicated as facilitating tumorigenesis, angiogenesis and metastasis. However, the effect of adiponectin on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has remained largely a mystery. In the present study, we have shown a clinical correlation between adiponectin and VEGF-C, as well as tumour stage, in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knock down inhibited lymphangiogenesis in vitro and in vivo We also found that adiponectin-induced VEGF-C is mediated by the calmodulin-dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK) and p38 signaling pathway. Furthermore, the expression of miR-27b was negatively regulated by adiponectin via the CaMKII, AMPK and p38 cascade. The present study is the first to describe the mechanism of adiponectin-promoted lymphangiogenesis by up-regulating VEGF-C expression in chondrosarcomas. Thus, adiponectin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis.
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Proteínas Quinasas Activadas por AMP/metabolismo , Adiponectina/metabolismo , Condrosarcoma/metabolismo , Linfangiogénesis , MicroARNs/metabolismo , Factor C de Crecimiento Endotelial Vascular/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Adiponectina/genética , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Línea Celular Tumoral , Condrosarcoma/enzimología , Condrosarcoma/genética , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Desnudos , MicroARNs/genética , Factor C de Crecimiento Endotelial Vascular/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Chondrosarcoma is a highly malignant cartilage-forming bone tumor that has the capacity to invade locally and cause distant metastasis. Moreover, chondrosarcoma is intrinsically resistant to conventional chemotherapy or radiotherapy. The novel benzofuran derivative, BL-038 (2-amino-3-(2,6-dichlorophenyl)-6-(4-methoxyphenyl)benzofuran-4-yl acetate), has been evaluated for its anticancer effects in human chondrosarcoma cells. BL-038 caused cell apoptosis in two human chondrosarcoma cell lines, JJ012 and SW1353, but not in primary chondrocytes. Treatment of chondrosarcoma with BL-038 also induced reactive oxygen species (ROS) production. Furthermore, BL-038 decreased mitochondrial membrane potential (MMP) and changed mitochondrial-related apoptosis, by downregulating the anti-apoptotic activity members (Bcl-2, Bcl-xL) and upregulating pro-apoptotic members (Bax, Bak) of the B-cell lymphoma 2 (Bcl-2) family of proteins, key regulators of the apoptotic machinery in cells. These results demonstrate that in human chondrosarcoma cells, the apoptotic and cytotoxic effects of BL-038 are mediated by the intrinsic mitochondria-mediated apoptotic pathway, which in turn causes the release of cytochrome c, the activation of caspase-9 and caspase-3, and the cleavage of poly (ADP-ribose) polymerase (PARP), to elicit apoptosis response. Our results show that the benzofuran derivative BL-038 induces apoptosis in chondrosarcoma cells.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Benzofuranos/farmacología , Caspasas/metabolismo , Mitocondrias/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Antineoplásicos/química , Proteínas Reguladoras de la Apoptosis/metabolismo , Benzofuranos/química , Western Blotting , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Condrosarcoma/metabolismo , Condrosarcoma/patología , Citocromos c/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Estructura Molecular , Poli(ADP-Ribosa) Polimerasas/metabolismoRESUMEN
PURPOSE: Bone mineral density changes with tamoxifen treatment have been reported in pre- and post-menopausal women with breast cancer. However, there remains controversy as to whether tamoxifen significantly reduces fracture rates in different age groups. Breast cancer occurs at 10-20 years younger in Asian women compared with Western women. Therefore we conducted this population-based case-control study to determine whether or not tamoxifen use is associated with osteoporotic fractures. PATIENTS AND METHODS: We selected 75488 women with breast cancer with no prior history of fractures from the Longitudinal Health Insurance Database for Catastrophic Illness Patients in 2000-2011. They were followed from the date of the diagnosis of breast cancer to the date a hip, vertebral or wrist fracture occurred. Because the use of tamoxifen was a time-dependent variable, we used a Cox proportional hazard model with time-dependent exposure covariates to estimate the risk of a fracture. RESULTS: There were 50257 and 25231 women with breast cancer who did and did not receive tamoxifen treatment, respectively. The tamoxifen users had lower risks for overall fractures with hazard ratios (HRs) of 0.52 and 0.59 in the crude and adjusted models (95 % CI = 0.45-0.61 and 0.51-0.69), respectively. They also had lower risks for hip (HR = 0.55, 95 % CI = 0.45-0.67) and vertebral (HR = 0.64, 95 % CI = 0.50-0.82) fractures in the adjusted model. The risk of fractures decreased with an increasing dosage of tamoxifen. Regardless of the age group, the tamoxifen users had a lower risk of fractures than the non-users. CONCLUSION: In this Asian population-based case-control study, tamoxifen use was associated with a reduction in osteoporotic fractures, especially in hip fractures.
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Antineoplásicos Hormonales/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Fracturas Osteoporóticas/prevención & control , Tamoxifeno/uso terapéutico , Factores de Edad , Anciano , Densidad Ósea/efectos de los fármacos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Fracturas de Cadera/epidemiología , Fracturas de Cadera/prevención & control , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Fracturas Osteoporóticas/diagnóstico , Fracturas Osteoporóticas/epidemiología , Modelos de Riesgos Proporcionales , Factores Protectores , Factores de Riesgo , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/prevención & control , Taiwán/epidemiología , Factores de Tiempo , Traumatismos de la Muñeca/epidemiología , Traumatismos de la Muñeca/prevención & controlRESUMEN
BACKGROUND: Diabetes is an independent risk factor of osteoarthritis (OA). Angiogenesis is essential for the progression of OA. Here, we investigated the intracellular signaling pathways involved in high glucose (HG)-induced vascular endothelial growth factor (VEGF) expression in human synovial fibroblast cells. METHODS: HG-mediated VEGF expression was assessed with qPCR and ELISA. The mechanisms of action of HG in different signaling pathways were studied using Western blotting. Knockdown of proteins was achieved by transfection with siRNA. Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the VEGF promoter. RESULTS: Stimulation of OA synovial fibroblasts (OASF) with HG induced concentration- and time-dependent increases in VEGF expression. Treatment of OASF with HG increased reactive oxygen species (ROS) generation. Pretreatment with NADPH oxidase inhibitor (APO or DPI), ROS scavenger (NAC), PI3K inhibitor (Ly294002 or wortmannin), Akt inhibitor, or AP-1 inhibitor (curcumin or tanshinone IIA) blocked the HG-induced VEGF production. HG also increased PI3K and Akt activation. Treatment of OASF with HG increased the accumulation of phosphorylated c-Jun in the nucleus, AP-1-luciferase activity, and c-Jun binding to the AP-1 element on the VEGF promoter. CONCLUSIONS: Our results suggest that the HG increases VEGF expression in human synovial fibroblasts via the ROS, PI3K, Akt, c-Jun and AP-1 signaling pathway. GENERAL SIGNIFICANCE: We link high glucose on VEGF expression in osteoarthritis.
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Fibroblastos/efectos de los fármacos , Glucosa/farmacología , Especies Reactivas de Oxígeno/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Acetilcisteína/farmacología , Androstadienos/farmacología , Cromonas/farmacología , Curcumina/farmacología , Relación Dosis-Respuesta a Droga , Fibroblastos/metabolismo , Fibroblastos/patología , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Humanos , Cápsula Articular/efectos de los fármacos , Cápsula Articular/metabolismo , Cápsula Articular/patología , Morfolinas/farmacología , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismo , Osteoartritis/patología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación , Cultivo Primario de Células , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-jun/agonistas , Proteínas Proto-Oncogénicas c-jun/genética , Proteínas Proto-Oncogénicas c-jun/metabolismo , ARN Interferente Pequeño/genética , Especies Reactivas de Oxígeno/agonistas , Transducción de Señal/efectos de los fármacos , Factor de Transcripción AP-1/antagonistas & inhibidores , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo , WortmaninaRESUMEN
INTRODUCTION: To determine risk factors for subsidence in patients treated with anterior cervical discectomy and fusion (ACDF) and stand-alone polyetheretherketone (PEEK) cages. MATERIALS AND METHODS: Records of patients with degenerative spondylosis or traumatic disc herniation resulting in radiculopathy or myelopathy between C2 and C7 who underwent ACDF with stand-alone PEEK cages were retrospectively reviewed. Cages were filled with autogenous cancellous bone harvested from iliac crest or hydroxyapatite. Subsidence was defined as a decrease of 3 mm or more of anterior or posterior disc height from that measured on the postoperative radiograph. Eighty-two patients (32 males, 50 females; 182 treatment levels) were included in the analysis. RESULTS: Most patients had 1-2 treatment levels (62.2 %), and 37.8 % had 3-4 treatment levels. Treatment levels were from C2-7. Of the 82 patients, cage subsidence occurred in 31 patients, and at 39 treatment levels. Multivariable analysis showed that subsidence was more likely to occur in patients with more than two treatment levels, and more likely to occur at treatment levels C5-7 than at levels C2-5. Subsidence was not associated with postoperative alignment change but associated with more disc height change (relatively oversized cage). CONCLUSION: Subsidence is associated with a greater number of treatment levels, treatment at C5-7 and relatively oversized cage use.
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Materiales Biocompatibles , Vértebras Cervicales/cirugía , Desplazamiento del Disco Intervertebral/cirugía , Cetonas , Polietilenglicoles , Falla de Prótesis/etiología , Fusión Vertebral/instrumentación , Espondilosis/cirugía , Adulto , Anciano , Benzofenonas , Discectomía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polímeros , Estudios Retrospectivos , Factores de Riesgo , Fusión Vertebral/métodos , Resultado del TratamientoRESUMEN
Osteoclast activity plays a crucial role in the pathological mechanisms of osteoporosis and bone remodeling. The treatment of these disorders involves the use of pharmacological medicines that work by inhibiting the activity of osteoclasts. Nevertheless, the prevalent and infrequent negative consequences of current antiresorptive and bone anabolic treatments pose significant drawbacks, hence restricting their prolonged administration in patients, particularly those who are elderly and/or suffer from many medical conditions. We are currently in the process of creating a new molecule called N-(4-methoxyphen) methyl caffeamide (MPMCA), which is a derivative of caffeic acid. This compound has shown potential in preventing the production of osteoclasts and causing existing osteoclasts to undergo cell apoptosis. Our investigation discovered that MPMCA hinders osteoclast function via suppressing the MAPK pathways. The expectation is that the findings of this study will stimulate the advancement of a novel approach to treating anti-resorption.
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Apoptosis , Ácidos Cafeicos , Osteoclastos , Osteogénesis , Ácidos Cafeicos/farmacología , Osteogénesis/efectos de los fármacos , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Apoptosis/efectos de los fármacos , Resorción Ósea/terapia , Células RAW 264.7 , Animales , Ratones , Línea Celular , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismoRESUMEN
Low back pain stands as a significant factor in disability, largely resulting from intervertebral disc degeneration (IVDD). High glucose (HG) levels have been implicated in the pathogenesis of IVDD. However, the detailed mechanism of HG in IVDD is largely unknown. Our clinical results revealed that fibrosis markers such as CTGF, Col1a1, ATF4, and EIF2 are highly expressed in advanced-stage IVDD patients. Stimulation of human annulus fibrosus cells (HAFCs) with HG, but not mannitol, promotes fibrosis protein production. Ingenuity Pathway Analysis in the GSE database found that the mTOR, PKCδ, and NF-κB pathways were significantly changed during IVDD. The mTOR, PKCδ, and NF-κB inhibitors or siRNAs all abolished HG-induced fibrosis protein production. In addition, treatment of HAFCs with HG enhances the activation of mTOR, PKCδ, and NF-κB pathways. Thus, HG facilitates fibrosis in IVDD through mTOR, PKCδ, and NF-κB pathways. These results underscore the critical role of HG as a fibrotic factor in the progression of IVDD.
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Anillo Fibroso , Fibrosis , Glucosa , FN-kappa B , Proteína Quinasa C-delta , Transducción de Señal , Serina-Treonina Quinasas TOR , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Proteína Quinasa C-delta/metabolismo , Fibrosis/metabolismo , FN-kappa B/metabolismo , Glucosa/metabolismo , Anillo Fibroso/metabolismo , Anillo Fibroso/patología , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patología , Masculino , Femenino , Persona de Mediana Edad , Células Cultivadas , AdultoRESUMEN
Antibiotic cement articulating spacers eradicate infection during a two-stage revision for advanced septic hip arthritis (ASHA); however, mechanical complications have been reported. We hypothesized that the rate of mechanical complications would be lower in medullary-sparing (MS) than in non-medullary-sparing (n-MS) articulating spacers. A retrospective study of ASHA using n-MS or MS spacers was conducted between 1999 and 2019. The rate of mechanical complications and reoperation and risk factors for mechanical complications were analyzed. The cohort included 71 n-MS and 36 MS spacers. All patients were followed up for 2 years. The rate of spacer dislocation was lower in MS (0%) than in n-MS spacers (14.1%; p = 0.014). The reoperation rate for mechanical complications was lower in MS (0%) than in n-MS spacers (12.7%; p = 0.019). The rate of a diaphyseal stem during reimplantation was lower in MS (0%) than in n-MS spacers (19.4%; p = 0.002). The identified risk factors for n-MS spacer dislocation were postoperative under-restored femoral head diameter ≥3 mm, femoral offset ≥3 mm, and surgical volume (≤6 resection arthroplasties per year). Both spacers controlled infection. However, MS spacers had a lower spacer dislocation and reoperation rate and avoided the diaphyseal stem during reimplantation. We recommend using MS spacers to restore native femoral head diameter and femoral offset when ASHA is treated by surgeons with lower surgical volumes.