Methylene blue relieves the development of osteoarthritis by upregulating lncRNA MEG3

Abstract

Methylene blue (MB) is a long-term inhibitor of peripheral nerve axons, thereby alleviating or permanently eliminating pain. However, it remains unknown whether MB is safe and effective method of treating osteoarthritis (OA). MB was injected into the knee joints of rabbits and they were monitored for any histological structural changes. The results revealed no evident changes in the histological structure of the normal knee joint following injection of 1 mg/kg MB at 1, 4, 8 and 24 weeks post-injection. Compared with the vehicle control, MB treatment significantly enhanced the weight distribution and significantly decreased the swelling ratio of the rabbits. Additionally, levels of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) mRNA were significantly increased following treatment with MB, but the protein expression of P2X purinoceptor 3 (P2X3) was significantly suppressed compared with the vehicle control. The levels of interleukin (IL) 6, tumor necrosis factor (TNF)α, IL-1β and IL-8 were significantly suppressed following MB treatment, indicating that MB protects against OA progression. It was also revealed that MEG3 overexpression significantly suppresses levels of P2X3 protein. ELISA indicated that the MEG3-induced reduction of IL-6, TNFα, IL-1β and IL-8 expression was significantly reversed following P2X3 overexpression. Therefore, the results of the present study demonstrated that MB is an effective method of treating OA-associated pain by upregulating lncRNA MEG3 levels. Additionally, lncRNA MEG3 relieves the OA-associated pain and inflammation in a rabbit model of OA by inhibiting P2X3 expression.

MEG3 inhibits proliferation and promote apoptosis in osteoarthritis chondrocytes by miR-361-5p/wnt/β-catenin axis

“…A previous study indicates that MEG3 is down-regulated and inversely associated with vascular endothelial growth factor A levels in OA. [14]. In the current study, the RT-qPCR analysis showed that the expression of MEG3 in OA group was significantly decreased than that in normal group.…”

“…Su et al showed that MEG3 was suppressed and inversely related to vascular endothelial growth factor A levels in OA. [14]. Actually, the biological function of MEG3 is realized by targeting certain pathways such as wnt/β-catenin signaling pathway [15].…”

Comparative Study Regarding the Properties of Methylene Blue and Proflavine and Their Optimal Concentrations for In Vitro and In Vivo Applications

“…Due to the high affinity of MB for the nervous system, administration of this dye suppresses long-term peripheral nerve medulla pain and reduces the levels of inflammatory factors (e.g., IL-6, TNFα, IL-1β, and IL-8) without relevant histological intra-articular damage. The results obtained from this study are presented in Figure 5 [90]. There was another study which also reported the use of MB as an intraoperative stain, without excising the stained tissue.…”

Protocatechuic aldehyde mitigates hydrogen peroxide-triggered PC12 cell damage by down-regulating MEG3

“…Evidence revealed that MEG3 mediated ischaemic neuronal death through targeting miR-21/PDCD4 pathway [32]. Moreover, up-regulated MEG3 participated in the protective activity of methylene blue in osteoarthritis via affecting P2X3 expression [33]. Based on the above research foundation, we speculated that MEG3 might modulate the correlative downstream target miRNA or mRNA to affect the functions of PA in H 2 O 2 -damaged PC12 cells.…”