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OBJECTIVES: To investigate the associations of residential greenness with bone mineral density and incident osteoporosis, and further evaluate the potential modifying effect of genetic susceptibility. METHODS: We used the Normalised Difference Vegetation Index (NDVI) at various buffer distances, including 300 m (NDVI300m), 500 m (NDVI500m), 1000 m (NDVI1000m) and 1500 m (NDVI1500m), to serve as indicators of greenness. We fitted linear regression, logistic regression and Cox proportional hazard models to assess the associations of residential greenness with estimated bone mineral density (eBMD), prevalent osteoporosis and incident osteoporosis, respectively. With the Polygenic Risk Score (PRS) for osteoporosis, we further assessed the joint effects of genetic risk and greenness on the risk of osteoporosis. We conducted causal mediation analyses to explore potential mediators. RESULTS: Each IQR increase in NDVI300m was associated with 0.0007 (95% CI 0.0002 to 0.0013) increase in eBMD, 6% lower risk of prevalent osteoporosis (OR 0.94; 95% CI 0.92 to 0.97) and 5% lower risk of incident osteoporosis (HR 0.95; 95% CI 0.93 to 0.98). The joint effects of greenness and PRS on the risk of osteoporosis displayed a clear dose-response pattern. Compared with individuals exposed to low NDVI levels and high genetic risk, those exposed to high NDVI levels and low genetic risk had a 56% (95% CI 51% to 61%) lower risk of osteoporosis. The primary mediators in the association between greenness and incident osteoporosis were identified as PM2.5 and NO2. CONCLUSIONS: Residential greenness was associated with higher bone mineral density and decreased risk of incident osteoporosis.
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Contaminación del Aire , Osteoporosis , Humanos , Densidad Ósea/genética , Factores de Riesgo , Puntuación de Riesgo Genético , Osteoporosis/epidemiología , Osteoporosis/genética , China , Material ParticuladoRESUMEN
BACKGROUND: Limb salvage surgery is an important method for treating malignant tumors of the bone involving the adjacent parts of the major joints in children. This technique allows for preservation of limb function, especially in the lower limb. However, the reconstruction of the proximal end of the tibia after removing the tumor mass with a rational scale to preserve the total knee joint and reduce limb length discrepancy presents a challenge. CASE PRESENTATION: We present a case of osteosarcoma of the proximal tibia. After being treated with an extended tumor resection, the proximal tibia of the child was restructured using endoprosthetic replacement with epiphyseal preservation. This procedure preserves the entire articular surface and growth plate of the knee joint of the affected limb and provides a feasible alternative protocol for retaining the function and growth potential of the affected limb. The patient remained disease-free and normal limb motor function was observed during the 3.5 year follow-up since the initial surgery. CONCLUSIONS: Preservation of the epiphysis enabled our patient to perform better limb function after limb-saving surgery as a result of his undamaged knee joint and minimized limb-length discrepancy. We believe that endoprosthetic replacement with preservation of the epiphysis can provide the best strategy for reconstruction after resection of focal malignant tumors in long bones without epiphytic involvement.
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Neoplasias Óseas , Epífisis , Recuperación del Miembro , Osteosarcoma , Tibia , Humanos , Osteosarcoma/cirugía , Tibia/cirugía , Tibia/diagnóstico por imagen , Neoplasias Óseas/cirugía , Epífisis/cirugía , Masculino , Recuperación del Miembro/métodos , Niño , Procedimientos de Cirugía Plástica/métodos , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign bone tumor, it is also called "Nora's lesion". The lesion is characterized by heterotopic ossification of the normal bone cortex or parosteal bone. The etiology of BPOP is unclear and may be related to trauma. In most BPOPs, the lesion is not connected to the medullary cavity. Here we report an atypical case, characterized by reversed features compared to the typical BPOP, which demonstrated continuity of the lesion with the cavity. CASE PRESENTATION: An 11-year-old female child had a slow-growing mass on her right wrist for 8 months with forearm rotation dysfunction. Plain X-rays showed an irregular calcified mass on the right distal ulna, and computed tomography (CT) showed a pedunculated mass resembling a mushroom protruding into the soft tissue at the distal ulna. The medulla of this lesion is continuous with the medulla of the ulna. A surgical resection of the lesion, together with a portion of the ulnar bone cortex below the tumor was performed, and the final pathology confirmed BPOP. After the surgery, the child's forearm rotation function improved significantly, and there was no sign of a recurrence at 1-year follow-up. CONCLUSION: It is scarce for BPOP lesions to communicate with the medullary cavity. However, under-recognition of these rare cases may result in misdiagnosis or inappropriate treatment thereby increasing the risk of recurrence. Therefore, special cases where BPOP lesions are continuous with the medulla are even more important to be studied to understand better and master these lesions. Although BPOP is a benign tumor with no evidence of malignant transformation, the recurrence rate of surgical resection is high. We considered the possibility of this particular disease prior to surgery and performed a surgical resection with adequate safety margins. Regular postoperative follow-up is of utmost importance, without a doubt.
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Neoplasias Óseas , Cúbito , Humanos , Femenino , Niño , Cúbito/cirugía , Cúbito/diagnóstico por imagen , Cúbito/patología , Neoplasias Óseas/cirugía , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/patología , Tomografía Computarizada por Rayos X , Osteocondroma/cirugía , Osteocondroma/diagnóstico por imagen , Osteocondroma/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Suture knotting is the basis of surgical skills. In the process of surgical skills learning, the surrounding environment, especially the light, will affect the efficiency of learning. This study investigated the effect of optical environment on the learning of stitching and knotting skills. METHODS: A total of 44 medical students were randomly divided into four groups and participated in the study of suture knotting in four different optical environments. During the process, we assess objective pressure level by testing salivary amylase activity Likert scale and objective structured clinical examination (OSCE) was used to estimate the subjective psychological state and overall skill mastery in surgical suturing respectively. RESULTS: Under high illumination conditions (700 lx), the salivary amylase activity of the high color temperature group (6000 K) was significantly higher than that of the low color temperature group (4000 K) (p < 0.0001). Similarly, under low illumination (300 lx), the salivary amylase activity of the high color temperature group was also significantly higher than that of the low color temperature group (p < 0.05). The student under high illumination conditions (700 lx) and the low color temperature (6000 K) have an autonomy score between 37-45, which is significantly higher compared to the other three groups (p < 0.0001). Group 2 has an average OSCE score of 95.09, which were significantly higher than those of the other three groups (p < 0.05). CONCLUSION: High illumination combined with low color temperature is considered as the optimal training conditions, promoting trainees' optimism, reducing stress levels, and enhancing learning efficiency. These results highlight the pivotal role of light environment in improving the quality and efficiency of surgical skills training.
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Aprendizaje , Examen Físico , Humanos , Amilasas , Competencia Clínica , Técnicas de Sutura/educaciónRESUMEN
Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.
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Neoplasias Óseas , Osteosarcoma , Macrófagos Asociados a Tumores , Neoplasias Óseas/genética , Neoplasias Óseas/inmunología , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Humanos , Osteosarcoma/genética , Osteosarcoma/inmunología , Fosfatidilinositol 3-Quinasas/genética , Macrófagos Asociados a Tumores/inmunologíaRESUMEN
Osteoporosis is a common skeletal disorder characterized by low bone mass, defective bone microstructure, and increased risk of fracture. It's well known that excessive activation of osteoclasts plays a vital role in the pathogenesis of osteoporosis. Thus, inhibition of osteoclast formation and function might be a proving strategy for osteoporosis. In our study, for the first time we explored the effect of Stachydrine Hydrochloride in the treatment of osteoporosis. We demonstrated that SH markedly inhibited osteoclastogenesis and osteoclast function in vitro and effectively decrease bone resorption in vivo. These finding were further supported by changes in the NF-κB and p38 signaling pathways, which are classical downstream pathways of RANKL-mediated osteoclastogensis. Collectively, these data suggest the possible future use of SH to protect against bone loss in the treatment of osteoporosis.
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BACKGROUND: Nephropathy associated metabolic disorder induces high incidence of fragility fracture in end-stage renal disease (ESRD) patients. As the risk factors and prognosis of fragility fracture in ESRD patients are unclear, more research is needed. This study aimed to evaluate various risk factors for ESRD-related fragility fractures, explore factors affecting the prognosis of patients with such fractures, and provide information for prevention and treatment of renal osteopathy to improve the prognosis of patients. METHODS: In this retrospective case-control study, the case notes of 521 ESRD patients who received maintenance dialysis for at least 3 months were examined. Finally, 44 patients diagnosed with fragility fractures were assigned to the fragility fracture (FF) group and 192 patients were included in the control group (CG). Demographic information, underlying diseases, nutritional, bone metabolism, and renal function parameters, along with the number and causes of any deaths, were recorded for multiple statistical analysis. RESULTS: The FF group had increased incidences of essential hypertension and diabetes mellitus and higher serum calcium, corrected calcium, alkaline phosphatase, and hemoglobin levels. Immunoreactive parathyroid hormone (iPTH), total cholesterol (TC), and low density lipoprotein (LDL) levels were higher in the CG. Multivariate Cox regression analysis revealed that fragility fracture was an independent risk factor for all-cause mortality in ESRD patients (P < .001, RR: 4.877, 95% CI: 2.367-10.013). CONCLUSIONS: Essential hypertension and diabetes, high serum calcium and alkaline phosphatase levels, and reduced iPTH levels were risk factors for fragility fracture in ESRD patients. Maintaining iPTH and serum TC levels may protect against fragility fractures in them. Fragility fractures may yield poor prognosis and shorter lifespan. The presence of fragility fracture was an independent predictor of all-cause death in ESRD patients.
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Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/complicaciones , Fracturas Espontáneas/etiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Diálisis Renal , Anciano , Estudios de Casos y Controles , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/terapia , Femenino , Fracturas Espontáneas/epidemiología , Fracturas Espontáneas/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Osteoporosis is a common disease characterized by reduced bone mineral density and impaired bone strength and is currently one of the leading causes of fracture and morbidity among the elderly worldwide. The pathological generation of osteoclasts is an important event in the development of extensive bone resorption. Thus, the development of a drug that targets osteoclasts may be beneficial in treating osteoporosis. Accordingly, in this study, we investigated the effects of senkyunolide H (SNH), an active component extracted from ligusticum chuanxiong Hort, on osteoporosis through a series of in vivo and in vitro experiments. First, we found that SNH had a therapeutic effect in ovariectomized mice by inhibiting osteoclast formation. Then, the inhibitory effect on osteoclast differentiation was confirmed in vitro. Further western blotting analysis revealed that SNH downregulated receptor activator of nuclear factor (NF)-κΒ ligand-induced NF-κB signaling activation, c-Jun N-terminal kinase (JNK) in the mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) signaling pathway. These data indicated that SNH may be a potential treatment for postmenopausal osteoporosis.
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Benzofuranos/farmacología , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Animales , Benzofuranos/uso terapéutico , Huesos/diagnóstico por imagen , Huesos/patología , Diferenciación Celular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Osteoclastos/metabolismo , Osteoclastos/fisiología , Osteoporosis Posmenopáusica/diagnóstico por imagen , Osteoporosis Posmenopáusica/patología , Ovariectomía , Células RAW 264.7 , Microtomografía por Rayos XRESUMEN
Osteoporosis is a metabolic bone lesion in which the bone mass is reduced per unit volume due to increased bone resorption. Its main characteristics are bone pain and increasing danger of fragility fracture. Excessive osteoclast activation is known to be responsible for extensive bone resorption. Thus, inhibition of osteoclastic bone resorption and regulation of the bone microenvironment are vital treatment strategies for osteoporosis. For the first time, we investigated the effect of proanthocyanidins (PACs) extracted from grape seed, which significantly inhibited osteoclast formation and differentiation from bone marrow macrophages (BMMs) and the RAW264.7â¯cell line and efficiently attenuated osteoclastic bone resorption without toxicity. These findings were confirmed by changes in the NF-κB and JNK/mitogen-activated protein kinase (MAPK) signaling pathways, which are major and classical signaling pathways involved in RANKL-mediated osteoclastogenesis in vitro. The PACs inhibited osteoclast formation and differentiation by inhibiting the NF-κB and JNK signaling pathways and might be useful for the treatment of osteoporosis.
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Extracto de Semillas de Uva/uso terapéutico , MAP Quinasa Quinasa 4/metabolismo , FN-kappa B/metabolismo , Osteogénesis/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Proantocianidinas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Animales , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Resorción Ósea/patología , Extracto de Semillas de Uva/farmacología , Ratones , Ratones Endogámicos C57BL , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , Osteoporosis/metabolismo , Osteoporosis/patología , Proantocianidinas/farmacología , Células RAW 264.7RESUMEN
BACKGROUND: Chondrosarcoma is a malignant cartilaginous neoplasm of the bone which resistant to radiation therapy and chemotherapy. Cyclin-dependent kinase 4 (CKD4) is highly expressed in human cancer, and palbociclib, the inhibitor of CDK4 has been used clinically under FDA approval for application in cancer therapeutic remedies. However, the level of CDK4 and the treatment possibility in chondrosarcoma require further exploration. Thus, we aim to investigate the level of CDK4 and accompanying therapeutic effects of palbociclib in chondrosarcoma. METHODS: We used immunohistochemistric analysis to evaluate human CDK4 productions in chondrosarcoma tissues. The inhibitory expression of CDK4 by siRNA or palbociclib on cell proliferation, invasion, migration, apoptosis and cycle arrest of chondrosarcoma were determined by MTT, wound healing, transwell and flow cytometry. CDK4/Rb signaling pathway were determined by western blot and Immunofluorescence assay. The inhibition effect of palbociclib on tumor growth within the bone were determined by bioluminescence imaging in vivo. RESULTS: CDK4 was found to express significantly in human chondrosarcoma samples. The enhanced levels of CDK4 were interlinked with malignant metastasis and undesirable prognosis of chondrosarcoma patients. CDK4 was also highly expressed in human chondrosarcoma cell lines and its inhibition by specific siRNA and palbociclib lead to a decrease in cell proliferation, accompanied by the phosphorylation of Rb. Furthermore, palbociclib also induced cell cycle arrest in G1 phase and decreased cell migration and invasion via CDK4/Rb signaling pathway. Administration of palbociclib in vivo could reduce tumor burden in chondrosarcoma. CONCLUSIONS: In summary, these data highlight CDK4 inhibitors, such as palbociclib, as potential promising therapeutics in the treatment of human chondrosarcoma.
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Condrosarcoma/tratamiento farmacológico , Condrosarcoma/enzimología , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Terapia Molecular Dirigida , Piperazinas/uso terapéutico , Piridinas/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Condrosarcoma/genética , Condrosarcoma/patología , Quinasa 4 Dependiente de la Ciclina/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Metástasis de la Neoplasia , Fosforilación/efectos de los fármacos , Piperazinas/farmacología , Pronóstico , Piridinas/farmacología , Proteína de Retinoblastoma/metabolismo , Carga TumoralRESUMEN
We have previously demonstrated the pivotal role of Jnk-mediated Irf-3/c-Jun in regulating nuclear factor kappa-Β ligand (RANKL)-induced osteoclastogenesis. Here, we demonstrated that proanthocyanidins (PACs) target Irf-3 to alleviate breast cancer-induced activation of osteoclasts. We also found that PACs induced apoptosis of osteoclast precursors by upregulating the ratio of bax/bcl-2 and activating caspase-3 activity. Such bone protective effect also could be observed in a bone metastasis model of breast cancer. These findings provided a novel therapeutic intervention targeting abnormal bone metabolism to alleviate bone metastasis of breast cancer.
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Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Factor 3 Regulador del Interferón/metabolismo , Proantocianidinas/farmacología , Proteínas Proto-Oncogénicas c-jun/metabolismo , Animales , Apoptosis/efectos de los fármacos , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Medios de Cultivo Condicionados/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Factor 3 Regulador del Interferón/genética , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteogénesis/fisiología , Proteínas Proto-Oncogénicas c-jun/genéticaRESUMEN
Osteoblastic bone formation and osteoclastic bone resorption dynamically maintain the bone homeostasis; in the present study, we attempt to investigate the mechanism of the excessive activation of osteoclasts inducing the deregulation of bone homeostasis from the perspective of non-coding RNA regulation. Differentially expressed patterns of circRNAs were examined in non-treated and RANKL + CSF1-treated bone marrow monocyte/macrophage (BMM) cells and differentially-expressed miRNAs during osteoclast differentiation were analyzed and identified. We found that circRNA_28313 was significantly induced by RANKL + CSF1 treatment. circRNA_28313 knockdown significantly inhibited RANKL + CSF1-induced differentiation of osteoclasts within BMM cells in vitro, while suppressed ovariectomized (OVX)-induced bone resorption in mice in vivo. Via bioinformatics analyses, it has been demonstrated that miR-195a might bind to circRNA_28313 and CSF1 and together form a circRNA-miRNA-mRNA network. circRNA_28313 relieves miR-195a-mediated suppression on CSF1 via acting as a ceRNA, therefore modulating the osteoclast differentiation in BMM cells. In conclusion, circRNA_28313, miR-195a, and CSF1 form a ceRNA network to function in RANKL + CSF1-induced osteoclast differentiation, thus affecting OVX-induced bone absorption in mice.
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Resorción Ósea/genética , Resorción Ósea/patología , Diferenciación Celular/genética , Factor Estimulante de Colonias de Macrófagos/metabolismo , MicroARNs/metabolismo , Osteoclastos/patología , Ovariectomía , ARN Circular/metabolismo , Regiones no Traducidas 3'/genética , Animales , Secuencia de Bases , Células de la Médula Ósea/metabolismo , Modelos Animales de Enfermedad , Células HEK293 , Humanos , Macrófagos/metabolismo , Ratones Endogámicos C57BL , MicroARNs/genética , Osteoclastos/metabolismo , Osteoporosis/genética , Osteoporosis/patología , ARN Circular/genéticaRESUMEN
OBJECTIVE: To explore the effect of application of soft tissue loosening and acetabular reconstruction in hip replacement for patients with severe femoral head necrosis on joint function.â© Methods: From June 2012 to August 2016, 68 patients with severe femoral head necrosis (Ficat III, IV) underwent total hip replacement with soft tissue release and acetabular reconstruction at the Second Xiangya Hospital of Central South University. Total hip replacement is performed by the posterolateral approach. The acetabulum was rebuilt and the length of the affected limb was prolonged after clearing the scar tissue, proliferating the epiphysis, releasing the abductor muscle group and the adductor muscle group, dissecting the soft tissue around the acetabulum. One year after surgery, Harris score, X-ray positive lateral radiograph for the affected side and full-length X-ray examination for both lower extremities were performed to evaluate the curative effect.â© Results: The postoperative follow-up time ranged from 1.0 to 5.5 years. All patients' femoral heads returned to normal anatomical position and the affected limb length was restored to 1.5-3.5 cm; all patients did not damage the sciatic nerve. The Harris scores for 68 patients increased from 38.6±7.5 to 78.2±5.7 (P=0.029) in the first year after surgery.â© Conclusion: During hip replacement surgery for severe femoral head necrosis, soft tissue dissection and acetabular reconstruction can be used to ensure anatomical reconstruction for the acetabular fossa and to improve abductor function.
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Artroplastia de Reemplazo de Cadera , Necrosis de la Cabeza Femoral , Acetábulo , Cabeza Femoral , Necrosis de la Cabeza Femoral/cirugía , Estudios de Seguimiento , Humanos , Radiografía , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: Drug resistance is the main difficulty for the current treatment for osteosarcoma. Cluster of differentiation 44 (CD44) is a receptor for hyaluronic acid (HA) and HA-binding has been proven to participate in various biological tumor activities, including tumor progression, metastasis and drug resistance. In this study, we aimed to determine the effects of CD44 on migration, invasion, proliferation, and the drug-sensitivity of osteosarcoma. METHODS: 96 human osteosarcoma tissues from 56 patients were collected to evaluate the expression of CD44 in osteosarcoma tissue by immunohistochemistry. CRISPR-Cas9 system was used to specifically silence CD44 in drug-resistant cell lines (KHOSR2 and U-2OSR2). The migration and invasion activities of cells was demonstrated by wound healing and transwell invasion assay. The proliferation speed of the cells was detected under 3D cell culture condition. Drug resistance of cells was detected by MTT and drug uptake assay. RESULTS: The immunohistochemistry results demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis, recurrence and drug resistance in patients with osteosarcoma. After knocking-out of CD44 by the CRISPR-Cas9 system, not only the migration and invasion activities of osteosarcoma cells were significantly inhibited, but the drug sensitivity was also enhanced. CONCLUSION: CD44 silencing could inhibit the development of osteosarcoma migration, invasion, proliferation and ameliorate drug resistance to current treatment in osteosarcoma. This study applies new strategy to target CD44, which may improve the prognosis of osteosarcoma.
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Neoplasias Óseas/genética , Sistemas CRISPR-Cas , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Receptores de Hialuranos/genética , Osteosarcoma/genética , Adolescente , Adulto , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Línea Celular Tumoral , Niño , Preescolar , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Femenino , Humanos , Lactante , Masculino , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Invasividad Neoplásica/prevención & control , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Adulto JovenRESUMEN
The biological activities of lanthanum chloride (LaCl3 ) and the molecular mechanisms of action underlying its anti-inflammatory, anti-hyperphosphatemic, and osteoblast-enhancing effects have been studied previously, but less is known about the effects of LaCl3 on osteoclasts. The present study used in vivo and in vitro approaches to explore the effects of LaCl3 on osteoclasts and osteolysis. The results indicated that LaCl3 concentrations that were non-cytotoxic to mouse bone marrow-derived monocytes attenuated receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis, bone resorption, mRNA expression of osteoclastogenic genes in these cells, including cathepsin K, calcitonin receptor, and tartrate-resistant acid phosphatase (TRAP). Further, LaCl3 inhibited RANKL-mediated activation of the nuclear factor-κB (NF-κB) signaling pathway, and downregulated mRNA and protein levels of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), and c-fos. In vivo, LaCl3 attenuated titanium (Ti) particle-induced bone loss in a murine calvarial osteolysis model. Histological analyses revealed that LaCl3 ameliorated bone destruction and decreased the number of TRAP-positive osteoclasts in this model. These results demonstrated that LaCl3 inhibited osteoclast formation, function, and osteoclast-specific gene expression in vitro, and attenuated Ti particle-induced mouse calvarial osteolysis in vivo, where the inhibition of NF-κB signaling and downregulation of NFATc1 and c-fos played an important role.
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Lantano/farmacología , FN-kappa B/metabolismo , Factores de Transcripción NFATC/metabolismo , Osteoclastos/efectos de los fármacos , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/patología , Diferenciación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Ratones , Osteoclastos/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ligando RANK/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Patients with melanoma are supposed to develop spontaneous immune responses against specific tumor antigens. However, several mechanisms contribute to the failure of tumor antigen-specific T cell responses, inducing immune escape. Importantly, immunosuppression mediated by regulatory T cells (Tregs) in tumor lesions is a dominant mechanism of tumor immune evasion. Based on this information, several therapies targeting Tregs such as cyclophosphamide, IL-2-based therapies, and antibodies against the surface molecular of Tregs have been developed. However, only some of these strategies showed clinical efficacy in patients with melanoma in spite of their success in shifting immune systems to antitumor responses in animal models. In the future, strategies specifically depleting local Tregs, inhibiting Treg migration to the tumor lesion, and Treg depletion in combination with other chemotherapies or immune modulation will hopefully bring benefits to melanoma patients.
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Melanoma/terapia , Neoplasias Cutáneas/terapia , Linfocitos T Reguladores/inmunología , Animales , Anticuerpos Monoclonales/química , Antígenos de Neoplasias/inmunología , Antígeno CTLA-4/metabolismo , Movimiento Celular , Ciclofosfamida/uso terapéutico , Modelos Animales de Enfermedad , Humanos , Sistema Inmunológico , Tolerancia Inmunológica , Inmunoterapia/métodos , Interleucina-2/metabolismo , Melanoma/inmunología , Melanoma/patología , Neoplasias Cutáneas/inmunologíaRESUMEN
Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure.
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Glucósidos/farmacología , Taninos Hidrolizables/farmacología , Macrófagos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteogénesis , Osteólisis/tratamiento farmacológico , Ligando RANK/metabolismo , Actinas/metabolismo , Animales , Glucósidos/uso terapéutico , Taninos Hidrolizables/uso terapéutico , Sistema de Señalización de MAP Quinasas , Macrófagos/citología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/genética , FN-kappa B/metabolismo , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Osteoclastos/citología , Osteoclastos/metabolismo , Osteólisis/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Cráneo/citología , Cráneo/metabolismo , Titanio/farmacologíaRESUMEN
Recent advances in the management of bone tumors have led to a significant increase in the survival rates of patients with malignant bone tumors. Thus, limb salvage surgery has gained importance for preserving limb function in the management of bone tumors. However, surgery presents unique difficulties in terms of the biomechanics and obtaining a soft-tissue cover, such as when the ankle is involved in the primary malignant bone tumor. We report a case of chondrosarcoma of the distal tibia treated with wide en bloc resection arthrodesis and reconstruction of the defect using distraction osteogenesis, which offers an effective alternative protocol for limb salvage. The patient has remained disease free for 3 years since the initial surgery and can maintain normal limb athletic function.
Asunto(s)
Artrodesis/métodos , Neoplasias Óseas/cirugía , Condrosarcoma/cirugía , Osteogénesis por Distracción , Tibia/cirugía , Adulto , Neoplasias Óseas/patología , Condrosarcoma/patología , Humanos , Recuperación del Miembro , Masculino , Pronóstico , Tibia/patología , Adulto JovenRESUMEN
Periprosthetic infection remains a challenging clinical complication. We investigated the antibacterial properties of pure (99.9%) magnesium (Mg) in vitro and in an in vivo rat model of implant-related infection. Mg was highly effective against methicillin-resistant Staphylococcus aureus-induced osteomyelitis and improved new peri-implant bone formation. Bacterial icaA and agr RNAIII transcription levels were also assessed to characterize the mechanism underlying the antibacterial properties of the Mg implant.