RESUMEN
Osteoarthritis (OA) is characterized by articular cartilage degradation and joint inflammation. The purpose of the present study is to elucidate the role of the specific function of PRMT1 in chondrocytes and its association with the pathophysiology of OA. We observed that the expression of PRMT1 was apparently upregulated in OA cartilage, as well as in chondrocytes stimulated with IL-1ß. Additionally, knockdown of PRMT1 suppressed interleukin 1 beta (IL-1ß)-induced extracellular matrix (ECM) metabolic imbalance by regulating the expression of MMP-13, ADAMTS-5, COL2A1, and ACAN. Furthermore, silencing of PRMT1 dramatically declined the production of prostaglandin E2 (PGE2) and nitric oxide as well as the level of pro-inflammatory cytokine IL-6 and TNF-α. Mechanistic analyses further revealed that IL-1ß-induced activation of the Hedgehog/Gli-1 signaling is suppressed upon PRMT1 knockdown. However, the effects of inhibition of PRMT1-mediated IL-1ß-induced cartilage matrix degradation and inflammatory response in OA chondrocytes were obviously abolished by Hedgehog agonist Purmorphamine (Pur). Our data collectively suggest that silencing of PRMT1 exerts anti-catabolic and anti-inflammatory effects on IL-1ß-induced chondrocytes via suppressing the Gli-1 mediated Hedgehog signaling pathway, indicating that PRMT1 plays a critical role in OA development and serves as a promising therapeutic target for OA.
Asunto(s)
Cartílago/metabolismo , Condrocitos/metabolismo , Técnicas de Silenciamiento del Gen , Proteínas Hedgehog/metabolismo , Interleucina-1beta/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Proteínas Represoras/genética , Transducción de Señal , Proteína con Dedos de Zinc GLI1/metabolismo , Cartílago/patología , Condrocitos/patología , Proteínas Hedgehog/genética , Humanos , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Interleucina-1beta/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteínas Represoras/metabolismo , Proteína con Dedos de Zinc GLI1/genéticaRESUMEN
OBJECTIVE: To investigate the effect of ultrasound in the treatment of osteoarthritis of the knee. METHODS: Eighty-seven out- and in-patients with osteoarthritis of the knee (15 men and 72 women) underwent ultrasonic therapy from February to October 2010. The patients were randomly assigned to an ultrasound group (Group A) and a placebo group (Group B). Group A was offered ultrasonic therapy while Group B underwent mock treatment. The visual analogue scale (VAS) and Lequesne scores of the two groups before and after treatment were compared. The data were analyzed by normal distribution, Student's t-test and the rank sum test. The means during and after treatment of the VAS and Lequesne efficacy index of the treatment group were calculated and plotted on a bar graph. RESULTS: Single sample analysis of Groups A and B showed VAS efficacy index: mean = 0.3640, P= 0.000; Lequesne efficacy index, median = 0.3080, P= 0.000, and mean = 0.1000, P= 0.000; Lequesne efficacy index, mean = 0.0364, P= 0.024, respectively. Independent samples t test and rank sum test showed significant differences between the two groups, namely P= 0.000 for both the VAS and Lequesne curative effect indexes. The means of the VAS efficacy index of the treatment group increased during and after treatment. The means of the Lequesne efficacy index of the treatment group showed no apparent decrease by 28 days after treatment. CONCLUSION: Ultrasound treatment significantly alleviates joint symptoms, relieving joint swelling, increasing joint mobility and reducing inflammation, in osteoarthritis patients.
