Open AccessMicroRNA-183attenuates osteoarthritic pain by inhibiting theTGFα-mediatedCCL2/CCR2signalling axis
Author(s) -
Zirong Tao,
Yang Zhou,
Biyun Zeng,
Xucheng Yang,
Manman Su
Publication year - 2021
Publication title -
bone and joint research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.639
H-Index - 31
ISSN - 2046-3758
DOI - 10.1302/2046-3758.108.bjr-2019-0308.r2
Subject(s) - proinflammatory cytokine , trpv1 , chemokine , ccr2 , microrna , transforming growth factor , ccl2 , medicine , chemistry , microbiology and biotechnology , receptor , inflammation , chemokine receptor , biology , transient receptor potential channel , biochemistry , gene
Aims MicroRNA-183 ( miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 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 ( CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumour necrosis factor-α ( TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 ( TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 ( Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 ( CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, 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 miR-183 was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of miR-183 inhibited the expression of proinflammatory cytokines ( IL-6, IL-1β, TNF-α) and pain-related factors ( TRPV1, Nav1.3, Nav1.7, Nav1.8) in DRG. OA pain was relieved by miR-183-mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that miR-183 directly targeted TGFα.Conclusion Our data demonstrate that miR-183 can ameliorate OA pain by inhibiting the TGFα- CCL2/ CCR2 signalling axis, providing an excellent therapeutic target for OA treatment. Cite this article: Bone Joint Res 2021;10(8):548–557.