attenuates osteoarthritic pain by inhibiting the -mediated / signalling axis.

AIMS

MicroRNA-183 () is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of in OA pain and to investigate the underlying mechanisms.

METHODS

Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (), proinflammatory cytokines (interleukin (IL)-6, , and tumour necrosis factor-α ()), and pain-related factors (transient receptor potential vanilloid subtype-1 (), voltage-gated sodium 1.3, 1.7, and 1.8 (, , and )). Expression of in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 () levels were examined by immunoblot analysis and interaction between and , determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG.

RESULTS

was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of inhibited the expression of proinflammatory cytokines (, , ) and pain-related factors (, , , ) in DRG. OA pain was relieved by -mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that directly targeted .

CONCLUSION

Our data demonstrate that can ameliorate OA pain by inhibiting the -/ signalling axis, providing an excellent therapeutic target for OA treatment. Cite this article:  2021;10(8):548-557.