RESUMEN
Several cellular and molecular processes participate in the pathologic changes of osteoarthritis (OA). However, the core molecular regulators of these processes are unclear, and no effective treatment for OA disease has been developed so far. ANGPTL2 is well known for its tissue remolding and pro-inflammation properties. However, the role of ANGPTL2 in osteoarthritis (OA) still remains unclear. To explore the expression level of ANGPTL2 in human OA cartilage and investigate the function of ANGPTL2 in human chondrocytes injury, qRT-PCR, western blot and immunohistochemistry were employed to investigate the expression of ANGPTL2 between human OA and normal cartilage samples. Next, human primary chondrocytes were treated with IL-1ß to mimic OA progress in vitro, and the expression of ANGPTL2 were tested by qRT-PCR and western blot. Furthermore, the effect of ANGPTL2 in the expression of pro-inflammation cytokines (IL-1ß, IL-6), proteolytic enzymes (MMP-1, MMP-13) and component of the cartilage matrix (COL2A1 and aggrecan) in human primary chondrocyte were explored by gain-of-function and loss-of-function methods. Finally, the nuclear factor kappa B (NF-κB) and p38/MAPK signaling pathways were also tested by western blot analysis. In this study, firstly, the expression level of ANGPTL2 was elevated both in human OA cartilage samples and IL-1ß stimulated human chondrocytes. Secondly, ANGPTL2 upregulation promotes extracellular matrix (ECM) degradation and inflammation mediator production in human chondrocytes. Finally, ANGPTL2 activated the NF-κB and p38/MAPK signaling pathways via integrin α5ß1. This study, for the first time, highlights that ANGPTL2 secreted by human chondrocytes plays a negative role in the pathogenesis of osteoarthritis, and it may be a potential therapeutic target in OA.
Asunto(s)
Proteínas Similares a la Angiopoyetina/genética , Condrocitos/metabolismo , Condrocitos/patología , Interleucina-1beta/farmacología , Sistema de Señalización de MAP Quinasas , FN-kappa B/metabolismo , Regulación hacia Arriba/genética , Proteína 2 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina/metabolismo , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Cartílago/patología , Células Cultivadas , Condrocitos/efectos de los fármacos , Colágeno Tipo II/metabolismo , Humanos , Integrina alfa5beta1/metabolismo , Interleucina-6/biosíntesis , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metaloproteinasas de la Matriz/metabolismo , Osteoartritis/metabolismo , Osteoartritis/patología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: Cancer-related fatigue is one of the most common symptoms reported by cancer patients and is considered to be related to inflammation. OBJECTIVE: This study aimed to explore the effects of nutritional support based on the dietary anti-inflammatory index on cancer-related fatigue in lung cancer patients undergoing chemotherapy. METHODS: This was a randomized controlled trial with 106 lung cancer patients who were divided into either the anti-inflammatory diet group (n = 53) or the usual diet group (n = 53) for 3 months. The primary outcome was cancer-related fatigue. Secondary outcomes included high sensitivity C-reactive protein (hs-CRP) concentrations, nutritional status, and quality of life. Repeated-measures analysis of variance was used to examine the effectiveness of this intervention. RESULTS: The anti-inflammatory diet improved fatigue (-1.99 ± 1.78, P < .001), hs-CRP levels (-4.15 [-11.87, -0.58], P < .001), Patient-Generated Subjective Global Assessment (-2.53 ± 3.11, P = .030), and albumin concentrations (2.83 ± 0.59, P < .001) compared with the usual diet after 3 months. Simultaneously, in the repeated-measures analysis of variance, the differences in fatigue ( F = 5.536, P < .001), hs-CRP levels ( F = 6.918, P < .001), and albumin concentrations ( F = 2.727, P = .048) were statistically significant for the group-by-time interaction. CONCLUSION: The study provided evidence for the positive effect of nutritional support based on the dietary anti-inflammatory index on cancer-related fatigue, hs-CRP levels, nutritional status, and quality of life in lung cancer patients undergoing chemotherapy. IMPLICATION FOR PRACTICE: With an anti-inflammatory diet, nurses can help these patients improve their overall quality of life.
Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Proteína C-Reactiva/análisis , Calidad de Vida , Dieta/efectos adversos , Apoyo Nutricional , Antiinflamatorios , Fatiga/etiologíaRESUMEN
Cartilage degeneration is a basic pathological feature of osteoarthritis (OA), and there is growing evidence that it is associated with inflammation. ACY-1215, a selective HDAC6 inhibitor, has been reported to have anti-inflammatory effects. Here, we investigated the anti-inflammatory and chondroprotective effects of ACY-1215 in IL-1ß-stimulated human primary chondrocytes and C28/I2 cells. The results suggested that ACY-1215 can markedly suppress the expression of inflammatory factors, including IL-1ß and IL-6 in human primary chondrocytes and C28/I2 cells. Furthermore, ACY-1215 exerts potent chondroprotection through the amelioration of cartilage degradation by inhibiting the expression of matrix-degrading proteases, including MMP-1 and MMP-13 in chondrocytes. These effects may be related to ACY-1215 induced down-regulation of NF-κB and STAT3 pathways in OA chondrocytes. Taken together, our results show that ACY-1215 may be a potential and promising therapeutic drug for the management of OA.