The Long Noncoding RNA MEG3 Is Downregulated and Inversely Associated with VEGF Levels in Osteoarthritis

Abstract

Osteoarthritis (OA) is becoming a major public health problem in China, especially considering the increase in average life expectancy of the population. Thus, enhanced understanding of the molecular changes associated with OA is urgently needed to develop more effective strategies for the diagnosis and treatment of this debilitating disease. LncRNAs play an important role in the processes of bone and cartilage development. Maternally expressed gene 3 (MEG3) is a maternally expressed lncRNA and may function as a tumor suppressor by inhibiting angiogenesis. OA is closely associated with angiogenesis and the inhibition of angiogenesis presents a novel therapeutic approach to reduce inflammation and pain in OA. In this study, we detected the mRNA expression of MEG3 and VEGF in articular cartilage samples from 20 OA patients and 10 healthy volunteers by real-time RT-PCR. VEGF protein is detected by ELISA in cartilage samples. The results show that human MEG3 is significantly downregulated in OA patients compared to normal cartilage samples. However, higher levels of VEGF mRNA and protein are found in OA compared to the control. Moreover, MEG3 levels are inversely associated with VEGF levels, suggesting that MEG3 may be involved in OA development through the regulation of angiogenesis.

Figure 1

Downregulation of lncRNA MEG3 expression in osteoarthritis (OA) cartilage samples. qRT-PCR analysis of MEG3 expression in cartilage samples from 10 healthy volunteers and 20 OA patients. GAPDH was the internal control (^⋆ P < 0.01).

Figure 2

Upregulation of VEGF mRNA and protein in OA cartilage samples. (a) qRT-PCR analysis was performed to examine MEG3 RNA levels in cartilage tissues from 20 OA patients and 10 controls. The results shown are from three independent qRT-PCR runs and are reported as the mean ± SD. ^⋆ P < 0.01. (b) The cartilage tissues from 20 OA patients and 10 controls were homogenized in buffer, and concentrations of immunoreactive VEGF were determined in homogenates by ELISA that detects all VEGF splice variants. The results shown are from three repetitions and are reported as the mean ± SD. ^⋆ P < 0.01.

Figure 3

The correlation of MEG3 with VEGF. Pearson correlation coefficient was calculated in SAS 9.3 as a measure of the degree of linear dependence between VEGF and MEG3 in OA group.