Study on the effects and mechanism of metformin on bone destruction induced by adjuvant arthritis in rats

ObjectiveTo investigate the effects and mechanism of metformin on bone destruction in rheumatoid arthritis(RA).

MethodsThe adjuvant arthritis(AA) models with complete Freund's adjuvant(CFA) were established in rats.The systemic inflammation score was used to evaluate the effects of different doses of metformin on inflammation in AA rats; the ankle and foot of each group were examined using X-ray imaging; ELISA was used to measure the serum calcium, phosphorus, osteoprotectin(OPG), nuclear factor κB receptor activator ligand(RANKL) in peripheral blood of rats; the expression levels of AMP-activated protein kinase(AMPK), interleukin-6(IL-6) and tumor necrosis factor α(TNF-α) were measured by immunohistochemistry.The effects of metformin on bone destruction in rats was evaluated.

ResultsMetformin could improve the systemic inflammatory response, and reduce paw swelling in AA rats, especially at high dose.All dose metformin groups could significantly improve the local bone mineral density and bone destruction in AA rats.The serum levels of calcium and phosphorus ion increased in high-dose metformin group.Different doses of metformin could increase the serum OPG level, and decrease the serum RANKL level.Compared with the model group, metformin could increase the protein expression of AMPK, decrease the protein expression of IL-6 and TNF-α, and the differences of which were statistically significant(P<0.05 to P<0.01).

ConclusionsMetformin plays a protective role on the bone destruction of RA.The mechanism of action may be related to the effects of anti-inflammation, regulation of serum bone metabolism index and activation of AMPK signaling pathway to affect the OPG-RANKL-RANK system.