Effect of alendronate sodium on chondrocytes in joint inflammation through down-regulation of microRNA-184 (miR-184)

Abstract

Chondrocytes participate in the progression of osteoarthritis (OA). Alendronate (ALN) can significantly improve the pathological changes of knee arthritis. However, whether alendronate affects chondrocytes of knee arthritis remains unclear. In this paper, the articular chondrocytes were assigned into model group. The inflammation cell model group was prepared using 10 ng/mL IL-1β, the alendronate group was co-cultured with 10 ng/mL IL-1β and 10 ng/mL ALN, and the miR-184 group was transfected with miR-184 siRNA on the basis of an inflammation model followed by the analysis of miR-184, BMP-2 and BMP-4 expression by real-time PCR, IL-1β and IL-22 levels were assayed by means of ELISA, Treg cells were detected by flow cytometry, IL-35 and TGF-β levels were checked by means of real-time PCR and western blot, and Wnt3, Wnt4 and β-Catenin protein levels were investigated by means of western blot. After alendronate and miR-184 siRNA were applied to the arthritis rat model, Treg cells was significantly decreased, IL-35 and TGF-β mRNA and secretion were reduced, miR-184 was down-regulated, BMP-2 and BMP-4 were upregulated, along with decreased IL-1β and IL-22 levels and expressions of Wnt3, Wnt4 and β-Catenin (P < 0.05). Alendronate inhibits Wnt/β-Catenin pathway by down-regulating miR-184, Treg cell and cytokines secretions these cytokines upregulate BMP-2 and BMP-4 in articular chondrocytes, and inhibits inflammatory factors secretion, thus ameliorating the progression of chondrocyte inflammation.