RESUMO
This study aimed to investigate the regulatory mechanism of MDM2 gene expression on cartilage cell proliferation in Osteoarthritis (OA) rats. For this purpose, 22 SD rats were randomly divided into normal control (10 cases) and treated (12 cases) groups. Treated group was used for OA modelling with the modified Hulth method. After a week, RT-PCR was used to detect MDM2 in cartilage tissue of rats, Wnt 1, Wnt 3 a, Wnt 10 b and ß-catenin genes mRNA expression. Rat chondrocytes were isolated and cultured, and the recombinant eukaryotic expression vector pcDNA3.1 myc-siRNA-MDM2-ß-catenin and co-expression plasmid pcDNA3.1 myc-siRNA-MDM2-ß-catenin was used to transfect chondrocytes and the proliferation and related gene expression levels of the transfected chondrocytes were detected by MTT method and RT-PCR. The results showed that compared with the control group, MDM2, Wnt 1, Wnt 3 a, Wnt 10b and ß-catenin genes in OA rat cartilage constructed by Hulth method were increased (p<0.05). The pcDNA3.1 myc-beta-catenin transfection slowed down the proliferation of OA chondrocytes, different from the non-transfected OA group (p<0.001), and increased Wnt 1, Wnt 3a, Wnt 10b and ß-catenin genes expression compared with the Control group (p<0.05), but did not affect the expression of MDM2. The transfection of siRNA-MDM2 was opposite to pcDNA3.1 myc-ß-catenin. The co-expression plasmid pcDNA3.1 myc-siRNA-MDM2-beta-catenin transfection did not affect the proliferation of OA chondrocytes. In general, the high expression of MDM2 in OA rats restricts the proliferation of chondrocytes, which may be related to the main pathogenesis of the occurrence and development of OA in vivo, and the regulation of MDM2 on the proliferation of chondrocytes may be achieved through the Wnt/ ß-catenin pathway.
Assuntos
Osteoartrite , beta Catenina , Animais , Proliferação de Células/genética , Células Cultivadas , Condrócitos/metabolismo , Osteoartrite/patologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , beta Catenina/genética , beta Catenina/metabolismoRESUMO
BACKGROUND: The incidence of insufficiency fracture (IF) at femoral neck is low, accounting for about 5% of all insufficiency fractures, and IF at bilateral femoral neck is less common with more occurrence in athlete or serviceman. With the aging of populations, more cases of bilateral femoral neck IF have occurred recently, while the standard clinical treatment still remains lacking due to the complexity of these patients. CASE PRESENTATION: A 55-year-old male patient complained pain in his bilateral hip, with no history of trauma, glucocorticoid hormone consumption or radiotherapy, and imaging examination revealed fracture nonunion and shortening in his left femoral neck, and double fracture line on the right femoral neck. The patient received a cementless THA for the left femoral neck fracture and conservative treatment for the right side, followed by Elcatonin injection and oral administration of Carbonate D3 Granules. After 4 months of fellow-up, the patient presented improved functional scorings in bilateral hip joints, with no signs of prothesis infection or loosening. CONCLUSION: We present a rare case of bilateral femoral neck IF in a middle-aged male and the treatment is successful. The timely CT and MRI examinations of bilateral hip joints for patients was necessary for orthopedists to select proper therapeutic regimen. In addition, the choice for therapeutic regimen of bilateral femoral IF should not only be based on the professional judgement of orthopedists, but also on the wishes of patients.
Assuntos
Artroplastia de Quadril/métodos , Fraturas do Colo Femoral/cirurgia , Fraturas de Estresse/cirurgia , Fraturas não Consolidadas/cirurgia , Adolescente , Idoso , Idoso de 80 Anos ou mais , Parafusos Ósseos , Calcitonina/administração & dosagem , Calcitonina/análogos & derivados , Hormônios e Agentes Reguladores de Cálcio/administração & dosagem , Colecalciferol/administração & dosagem , Tratamento Conservador , Feminino , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/tratamento farmacológico , Colo do Fêmur/cirurgia , Seguimentos , Fixação Interna de Fraturas/métodos , Fraturas de Estresse/diagnóstico por imagem , Fraturas de Estresse/tratamento farmacológico , Fraturas não Consolidadas/diagnóstico por imagem , Fraturas não Consolidadas/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: This study aimed to explore the mechanism of Bushen Huoxue decoction (BHD) in treating intervertebral disc degeneration using the network pharmacology method. METHODS: Using of oral bioavailability >30% and drug-likeness >0.18 as the screening standards, the effective components and targets of BHD were retrieved from the TCMSP database and the BATMAN-TCM database. The disease targets of intervertebral disc degeneration were retrieved from the GeneCards database. The Wayne map of the interaction targets of the effective components of BHD and intervertebral disc degeneration were drawn using R software. The protein-protein interaction (PPI) network of common targets was constructed using STRING software. The network map of the interaction targets of the effective components of BHD-intervertebral disc degeneration was drawn using Cytoscape3.7.2 software. The GO and KEGG enrichment analysis of the common targets of BHD and intervertebral disc degeneration was performed using R software and the related plug-ins to screen the potential pathways and analyze its mechanism. RESULTS: This study screened 164 effective components of BHD, 131 interaction targets, 626 targets for degenerative disc disease, and 31 common interaction targets. IL6, VEGFA, CASP3, EGFR, ESR1, and MAPK8 appeared more frequently. These were mainly enriched in the AGE-RAGE, TNF, PI3K Akt, and MAPK signaling pathways. CONCLUSIONS: BHD mainly intervenes in intervertebral disc degeneration through IL6, VEGFA, CASP3, EGFR, ESR1, and MAPK8. The mechanism of the intervention of BHD on intervertebral disc degeneration may be related to AGE-RAGE, TNF, PI3K Akt, MAPK, and other signal pathways.
Assuntos
Medicamentos de Ervas Chinesas , Degeneração do Disco Intervertebral , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Degeneração do Disco Intervertebral/tratamento farmacológico , Medicina Tradicional Chinesa , Fosfatidilinositol 3-QuinasesRESUMO
Osteoarthritis (OA) is a common clinical degenerative disease characterized by the destruction of articular cartilage, which has an increasing impact on people's lives and social economy. The pathogenesis of OA is complex and unclear, and there is no effective way to block its progress. The study of the pathogenesis of OA is the prerequisite for the early diagnosis and effective treatment of OA. To define the pathogenesis of OA, this review considers the pathological mechanism of OA that involves microRNA, lncRNA, and exosomes. More and more evidence shows that microRNA, lncRNA, and exosomes are closely related to OA. MicroRNA inhibits the target gene by binding to the 3'- untranslated region of the targets. LncRNA usually competes with microRNA to regulate the expression level of downstream genes, while exosomes, as a carrier of intercellular information transfer, transmit the biological information of mother cells to target cells, and the effect of exosomes secreted by different cells on OA are different. In this review, we emphasized that different microRNA, lncRNA, and exosomes have different regulatory effects on chondrocyte proliferation and apoptosis, extracellular matrix degradation and inflammation. Besides, we classified and analyzed these molecules according to their effects on the progress of OA. Based on the analysis of the reported literature, this review reveals some pathogenesis of OA, and emphasizes that microRNA, lncRNA, and exosomes have great potential to assist early diagnosis and effective treatment of OA.
Assuntos
Exossomos/metabolismo , MicroRNAs/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , RNA Longo não Codificante/metabolismo , Progressão da Doença , HumanosRESUMO
OBJECTIVE: To compare and analyze the clinical effects of external fixator and small splint fixator in the treatment of comminuted distal radius fracture in senile. METHODS: From 2005.6 to 2008.6, 74 senile patients (82 sides) with comminuted distal radius fractures were divided into external fixation group (34 cases 38 sides, 27 males and 7 females, with an average of 70.05 +/- 3.70 years) and small splint fixation group (40 cases 44 sides, 29 males and 11 females, with an average of 70.30 +/- 3.48 years). The loss of volar tilting angle and ulnar inclination angle after reduction and the function scores of carpal joint after removing the fixators were compared. RESULTS: One week after surgery, there was loss of volar tilting angle and ulnar inclination in small splint fixation (P < 0.01), and one month after removing the external fixator, the loss of angle was more obvious (P < 0.01); while the loss of angle in external fixation group was not significant (P > 0.05). After one month of removing the fixation, the functional score of wrist joint in external fixation group was obviously higher than that of the small splint fixation group (P < 0.05). CONCLUSION: The external fixator can be adopted to treat comminuted distal radius fractures in senile, which is able to decrease the reduction loss and helpful to functional recovery.