Methylene blue relieves the development of osteoarthritis by upregulating lncRNA MEG3

Area of Science:

• Biomedical Science
• Pharmacology
• Molecular Biology

Background:

• Osteoarthritis (OA) is a degenerative joint disease causing pain and inflammation.
• Methylene blue (MB) is a known inhibitor of peripheral nerve axons, used for pain management.
• The efficacy and safety of MB for OA treatment remain largely uninvestigated.

Purpose of the Study:

• To evaluate the safety and effectiveness of Methylene blue (MB) in treating osteoarthritis (OA) in a rabbit model.
• To investigate the molecular mechanisms underlying MB's potential therapeutic effects in OA.

Main Methods:

• MB was injected into the knee joints of rabbits, with histological analysis performed at various time points.
• Functional assessments included weight distribution and swelling ratio measurements.
• Molecular analyses involved quantifying long non-coding RNA (lncRNA) MEG3 mRNA, P2X purinoceptor 3 (P2X3) protein, and inflammatory cytokine (IL-6, TNFα, IL-1β, IL-8) levels.

Main Results:

• No significant histological changes were observed in normal rabbit knee joints post-MB injection.
• MB treatment improved weight distribution and reduced swelling ratio in OA rabbits.
• MB significantly increased lncRNA MEG3, suppressed P2X3 protein, and reduced inflammatory cytokine levels (IL-6, TNFα, IL-1β, IL-8).
• MEG3 overexpression inhibited P2X3, while P2X3 overexpression reversed MEG3-induced suppression of inflammatory cytokines.

Conclusions:

• Methylene blue (MB) is a safe and effective treatment for OA-associated pain in rabbits.
• MB upregulates lncRNA MEG3, which inhibits P2X3 expression, thereby alleviating OA pain and inflammation.
• The findings suggest a novel therapeutic pathway for OA involving MB and the MEG3/P2X3 axis.