RESUMO
Osteoarthritis (OA) is a common degenerative disease characterized by reducing articular chondrocytes and destruction of joint matrix, it's detailed pathogenesis remains unclear. Emerging evidences have demonstrated that long non-coding RNAs (lncRNAs) are closely related to the progression of OA. This study aims to explore the expression of long non-coding RNA LEMD1 antisense RNA 1 (LEMD1-AS1) in OA tissues and chondrocytes and investigate the possible mechanisms of LEMD1-AS1 in OA, which will provide a new target for the treatment of OA. In our study, LEMD1-AS1 and post-GPI attachment to protein (PGAP1) were lowly expressed, but miR-944 was highly expressed both in OA tissues and in Lipopolysaccharide (LPS) -treated chondrocytes detected by qRT-PCR. Over-expression of LEMD1-AS1 or down-regulation of miR-944 significantly promoted viability, proliferation and inhibited cell apoptosis, cell cycle arrest and inflammatory responses of chondrocytes treated with LPS by CCK-8, EdU, flow cytometry and an ELISA assay. Over-expression of LEMD1-AS1 or down-regulation of miR-944 remarkably increased the protein levels of PCNA, Ki-67, Cyclin A1, Cyclin B1, Cyclin D2 and Bcl-2, while decreasing the protein levels of p27, Bax, Cleaved-caspase-3 and Cleaved-caspase-9 in chondrocytes treated with LPS. LEMD1-AS1 bound to miR-944 and regulated its expression, and PGAP1 presented as a direct target gene of miR-944, which was confirmed by a dual-luciferase reporter assay. Inhibition of PGAP1 partially restored the effects of LEMD1-AS1/miR-944 on the proliferation, cell apoptosis, cell cycle distribution and inflammatory responses of LPS-treated chondrocytes. To conclude, the LEMD1-AS1/miR-944/PGAP1 axis may be a novel therapeutic candidate to target in OA treatment.
Assuntos
Proteínas de Membrana , MicroRNAs , Osteoartrite , Monoéster Fosfórico Hidrolases , RNA Longo não Codificante , Apoptose/genética , Proliferação de Células/genética , Condrócitos/metabolismo , Humanos , Inflamação/patologia , Lipopolissacarídeos/farmacologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoartrite/metabolismo , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: We examined the independent and cumulative associations of resting heart rate and pulse pressure with metabolic syndrome in Chinese rural population based on epidemiological research. METHODS: A total of 38,708 participants were derived from the Henan Rural Cohort study. Restricted cubic splines and logistic regression model were used to estimate the odds ratios and 95% confidence intervals of metabolic syndrome risk in relation to resting heart rate and pulse pressure. RESULTS: After adjusting for potential confounders, the odds ratio (95% confidence intervals) of resting heart rate and pulse pressure in the highest quartile with the risk of metabolic syndrome were 1.59 (1.48-1.70) and1.81 (1.67-1.95), respectively. Simultaneously, the cumulative effect analysis indicated that the adjusted the odd ratio of resting heart rate and pulse pressure in the highest quartile was 2.89 (2.40-3.47). Furthermore, there was a significantly additive interaction between resting heart rate and pulse pressure on the risk of metabolic syndrome. CONCLUSION: Increased resting heart rate and pulse pressure are associated with the higher risk of metabolic syndrome as well as the influences of resting heart rate with pulse pressure might cumulatively increase the risk of metabolic syndrome. However, the potential clinical application remains to be determined.
