RESUMO
OBJECTIVE@#To observe the effect of needle-knife on the chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis (KOA) based on the CircSERPINE2-miR-1271-5P-E26 specific transformation-related gene (ERG) axis, and to explore the mechanism of needle-knife for KOA.@*METHODS@#Thirty-six New Zealand white rabbits were randomly divided into a normal group, a model group, a needle-knife group and a sham needle-knife group, 9 rabbits in each group. The rabbits in the model group, the needle-knife group and the sham needle-knife group were treated with modified Videman method to prepare KOA model. After successful modeling, the rabbits in the needle-knife group were treated with needle-knife at cord adhesion and nodules near quadriceps femoris tendon and internal and external collateral ligament on the affected knee joint; the rabbits in the sham needle-knife group were treated with sham needle-knife baside the needle insertion point of the needle-knife group (needle-knife was only inserted, without any operation). The treatment was given once a week, 3 times in total. The Lequesne MG behavioral score was used to evaluate the knee joint damage in each group before and after intervention. After intervention, HE staining and transmission electron microscopy were used to observe the cartilage tissue morphology and ultrastructure of chondrocytes in the knee joint in each group; TUNEL method was used to detect the level of chondrocyte apoptosis in the knee joint; real-time fluorescence quantitative PCR was used to detect the expression of CircSERPINE2, miR-1271-5P and ERG mRNA in knee cartilage tissue in each group.@*RESULTS@#After intervention, compared with the normal group, the Lequesne MG behavioral score in the model group was increased (P<0.01). Compared with the model group and the sham needle-knife group, the Lequesne MG behavioral score in the needle-knife group was decreased (P<0.01). In the model group and the sham needle-knife group, the number of chondrocytes and organelles was decreased, the cell nucleus was shrunk, mitochondria was swelling or disappeared; in the needle-knife group, the number of chondrocytes and organelles was increased, the cell nucleus was not obviously shrunk and the mitochondria was not obviously swelling. Compared with the normal group, the level of chondrocyte apoptosis in the model group was increased (P<0.01); compared with the model group and the sham needle-knife group, the level of chondrocyte apoptosis in the needle-knife group was decreased (P<0.01, P<0.05). Compared with the normal group, the expression of CircSERPINE2 and ERG mRNA in the model group was decreased (P<0.01), and the expression of miR-1271-5P mRNA was increased (P<0.01); compared with the model group and the sham needle-knife group, the expression of CircSERPINE2 and ERG mRNA in the needle-knife group was increased (P<0.01), and the expression of miR-1271-5P mRNA was decreased (P<0.01).@*CONCLUSION@#Needle-knife could reduce the knee joint damage and chondrocyte apoptosis in KOA rabbits, which may be related to up-regulating the expression of CircSERPINE2 and ERG mRNA, and inhibiting the expression of miR-1271-5P mRNA.
Assuntos
Coelhos , Animais , Osteoartrite do Joelho/metabolismo , Condrócitos/metabolismo , Articulação do Joelho/cirurgia , Apoptose , MicroRNAs/genéticaRESUMO
Resumen: Objetivo: Analizar el nivel de citoquinas proinflamatorias en la grasa articular del paquete adiposo en pacientes con gonartrosis, en relación con la grasa subcutánea del muslo. Material y métodos: Efectuamos un estudio de grasa del paquete adiposo articular de la rodilla afectada de artrosis y de la grasa subcutánea del muslo del mismo lado, a la mayor distancia de la articulación en seis pacientes con gonartrosis grave, con una edad media de 68 años (rango: 55-81 años). De las muestras de grasa se obtuvieron las células mesenquimales progenitoras. Los sobrenadantes de células mesenquimales obtenidas se utilizaron para analizar factores inflamatorios (IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13, IL15) y angiogénicos (VEGF, PDGF bb), así como citoquinas inmunomoduladoras (IP-10 e INF-γ) y se compararon las medias de dos muestras. Resultados: El análisis cuantitativo reveló una disminución significativa (p < 0.05) de IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13 y un aumento de IL15 en la grasa de Hoffa frente al tejido adiposo subcutáneo. Del mismo modo, el análisis de factores angiógenicos como VEGF y PDGF bb, al igual que los factores IP-10 e INF-γ presentaron una disminución significativa en la grasa de Hoffa (p < 0.05) frente al tejido adiposo subcutáneo. Discusión: Las células mesenquimales del paquete adiposo articular de la rodilla artrósica grave muestran una disminución significativa de citoquinas inflamatorias, aun en el estado crónico, y una disminución significativa de factores angiogénicos y citoquinas inmunomoduladoras (IP10 e INF).
Abstract: Objective: To analyze the level of pro-inflammatory cytokines in osteoarthritis knee joint fat pad in relation to the subcutaneous fat of the thigh. Material and methods: We performed a study of fat of the knee joint adipose affected of osteoarthritis and subcutaneous fat of the thigh of the same side to the greater distance of the joint in six patients with severe gonarthrosis, with a mean age of 68 years (range: 55-81 years). From the fat samples the progenitor mesenchymal cells were obtained. The supernatants of mesenchymal cells obtained to analyze inflammatory factors (IL-1b, IL6, IL9, IL1ra, IL12, IL13, IL15) and angiogenic (VEGF, PDGF bb) and immunomodulatory cytokines (IP-10 and INF-γ) means of two samples. Results: Quantitative analysis revealed a significant (p < 0.05) decrease in IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13 and increase of IL15 in Hoffa fat pad versus subcutaneous adipose tissue. Likewise, the analysis of angiogenic factors such as VEGF and PDGF, as well as factors IP-10 and INF-γ presented a significant decrease (p < 0.05) in Hoffa fat pad versus subcutaneous adipose tissue. Discussion: Mesenchymal cells from the adipose tissue of the severe osteoarthritic knee show a significant decrease in inflammatory cytokines even in the chronic state and a significant decrease in angiogenic factors and immunomodulatory cytokines (IP10 and INF).
Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Citocinas/metabolismo , Osteoartrite do Joelho/metabolismo , Gordura Subcutânea/metabolismo , Coxa da Perna , Tecido Adiposo , Articulação do Joelho , Pessoa de Meia-IdadeRESUMO
Hernán Alessandri M.D. was an astounding clinician and a leading medical educator, born in Santiago in 1900 where he died in 1980. He received his medical degree at the University of Chile in 1923, became Professor of Clinical Medicine in 1932, Full Professor and Chair of Internal Medicine in 1944. At the Hospital del Salvador, in Santiago, he chaired a teaching Department and a Clinical Service that was an example for its academic environment and dedication to patients and students. From 1958 to 1962 he was Dean of the University of Chile Faculty of Medicine, conducting a reform of teaching curricula and organizing medical residency programs for the training of specialists, originally started in his own Service in 1952. The American College of Physicians awarded him the first foreign Honorary Membership. He was a founding Member of the Chilean Academy of Medicine (1964). In 1973 the University of Chile awarded him the Emeritus Professor status. He was considered by his peers, alumni and patients a brilliant clinician and an exceptional medical educator. Since 1980 a Social and Teaching Foundation bears his name and in 2014, with the occasion of the XXXV Chilean Congress of Internal Medicine, the Sociedad Médica de Santiago-Chilean Society of Internal Medicine created an annual lecture to render tribute to distinguished physicians and his name was one of the two selected to inaugurate them.