RESUMEN
In recent years, research on the mechanism of bone destruction in rheumatoid arthritis (RA) has remained in the initial stages, and the mechanism has not been fully elucidated to date. Recent studies have shown that long noncoding RNAs (lncRNAs) participate in RA bone destruction via autophagy, but the specific regulatory mechanism of lncRNA-mediated autophagy is unclear. Therefore, in this article, we review the mechanisms of lncRNA-mediated autophagy in fibroblast-like synoviocytes and chondrocytes in RA bone destruction. We explain that lncRNAs mediate autophagy and participate in many specific pathological processes of RA bone destruction by regulating signalling pathways and the expression of target genes. Specific lncRNAs can be used as markers for molecular diagnosis, mechanistic regulation, treatment and prognosis of RA.
Asunto(s)
Artritis Reumatoide , ARN Largo no Codificante , Sinoviocitos , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Artritis Reumatoide/metabolismo , Sinoviocitos/metabolismo , Transducción de Señal , Fibroblastos/metabolismo , Autofagia/genética , Proliferación Celular/genética , Células CultivadasRESUMEN
OBJECTIVE: To observe the effect of heat-tonifying needling on Keap1-Nrf2/ARE/HO-1 signal transduction pathway in knee synovium in rabbits with cold syndrome type rheumatoid arthritis (RA), so as to explore its mechanisms underl-ying improvement of RA. METHODS: New Zealand rabbits were randomly divided into normal control, RA model, uniform reinforcing-reducing acupuncture, twisting reinforcing acupuncture and heat-tonifying acupuncture groups, with 6 rabbits in each group. The cold syndrome type RA model was established by subcutaneous injection of mixture fluid of ovalbumin and Freund's complete adjuvant at the shoulder-back as well as injection of mixture of ovalbumin and normal saline into knee-joint cavity combined with ice-compress freezing. Acupuncture stimulation (uniform reinforcing-reducing, or twisting reinforcing or heat-tonifying) was applied to bilateral "Zusanli"(ST36) for 1 min with the needle retained for 30 min, once a day for 7 consecutive days. The general conditions of rabbits in each group were recorded, the thermal pain threshold (TPT) and perimeter of knee joints was measured. Conditions of the synovium in the knee cavity, hydrops, blood flow signal, articular surface, and related muscles were observed by using a color Doppler ultrasonic diagnostic apparatus, and the blood flow signals inside the synovium (image scores) were divided into 0 (no signals), I (1 or 2 dot-like signal), II (less than half) ad III (more than half). After H.E. staining, the pathological changes (0-3 points) were assessed according to the state of inflammatory cell infiltration, and hyperplasia of synovial matrix and coating cells. The expression levels of Keap1, Nrf2, HO-1 and GSH-PX1 mRNAs in the knee synovium were detected by quantitative real-time PCR, and the expression of knee synovial HO-1 protein was measured by Western blot. RESULTS: In comparison with the normal control group, the model group had a significant increase in the perimeter, pathological score, expression of Nrf2, HO-1 mRNAs and HO-1 protein (P<0.05), and an obvious decrease in the TPT, expression levels of Keap1 and GSH-PX1 mRNAs (P<0.05). Relevant to the model group, all the three acupuncture maneuvers reversed modeling-induced increase of perimeter and pathological score (P<0.05), decrease of TPT and expression of GSH-PX1 mRNA(P<0.05), further down-regulated expression of Keap1 mRNA (P<0.05), further up-regulated the expression of Nrf2, HO-1 mRNAs and HO-1 protein (P<0.05). The heat-reinforcing manipulation was significantly superior to uniform reinforcing-reducing and twirling reinforcing manipulations in up-regulating TPT, and expression of Nrf2 mRNA, GSH-PX1 mRNA, HO-1 mRNA and protein (P<0.05), and in down-regulating pathological score and Keap1 mRNA expression (P<0.05). CONCLUSION: Heat-tonifying, uniform reinforcing-reducing and twirling reinforcing needling manipulations may relieve pain and improve pathological state in RA rabbits, which may be associated with their functions in raising the ability of anti-oxidative stress by regulating Keap1-Nrf2/ARE/ HO-1 signaling pathway, the therapeutic effect of heat-tonifying needling is superior to that of uniform reinforcing-reducing and twirling reinforcing needling.
Asunto(s)
Terapia por Acupuntura , Artritis Reumatoide , Conejos , Animales , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Calor , Ovalbúmina/metabolismo , Artritis Reumatoide/genética , Artritis Reumatoide/terapia , Artritis Reumatoide/metabolismo , Transducción de Señal , Síndrome , Umbral del Dolor , ARN MensajeroRESUMEN
Oxalis articulata, an alien clonal plant species, is widely cultivated in China as an ornamental species, and has escaped and became naturalized. Belowground storage in tubers of O. articulata may play a key role for the potential invasion. In this study, we investigated the responses of its clonal resource storage strategy to mowing, aiming to uncover the mechanism underlying their invasion from a perspective of clonal storage. We examined the changes of biomass in different organs, biomass allocation, and several functional traits of roots, tubers and leaves in O. articulata by conducting a greenhouse experiment. The results showed that significant main and interactive effects of mowing intensity and mowing frequency on some functional traits of leaves and roots were found. In contrast, tuber biomass and total biomass did not vary under different mowing treatments. The frequent mowing significantly increased the biomass allocation to tubers. These findings demonstrated that clonal storage, to some extent, could enhance the resistance of O. articulata to environmental disturbance, which might promote its invasiveness.