Circ-SPG11 knockdown hampers IL-1\u03b2-induced osteoarthritis progression via targeting miR-337-3p/ADAMTS5

Yongqiang Liu,Fang Lei,Qian Li,Xuefeng Gao,Zhida Gao

doi:10.1186/s13018-021-02526-y

Abstract

BackgroundOsteoarthritis (OA) is responsible for the impotent disability in old people. Circular RNA (circRNA) has been reported to be related to the development of diseases. The lack of research on the role of circRNA spastic paraplegia 11 (circ-SPG11) results in conducting this study.MethodsThe expression of circ-SPG11, microRNA-337-3p (miR-337-3p), and aggrecanases like a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used to measure the protein expression of extracellular matrix (ECM) degradation-related markers and ADAMTS5. Ribonuclease R (RNase R) was applied to test the stability of circ-SPG11 in CHON-001 cells. The viability, apoptosis, TNF-α and IL-6 production were determined by cell counting kit-8 (CCK-8) assay, flow cytometry assay, and enzyme-linked immunosorbent assay (ELISA), respectively. Meanwhile, the interaction between miR-337-3p and circ-SPG11 or ADAMTS5 was respectively predicted by Circinteractome or Starbase2.0, which was further verified by dual-luciferase reporter system and RNA binding protein immunoprecipitation (RIP) assay.ResultsCirc-SPG11 and ADAMTS5 were upregulated and miR-337-3p was downregulated in OA tissues and OA model cells. Circ-SPG11 knockdown allayed interleukin 1β (IL-1β)-induced restraint in viability and promotion in apoptosis, TNF-α, and IL-6 generation and ECM degradation in CHON-001 cells. Anti-miR-337-3p or ADAMTS5 overexpression correspondingly reversed si-circ-SPG11 or miR-337-3p overexpression-mediated facilitation in viability, and inhibition in apoptosis, TNF-α and IL-6 generation and ECM degradation in OA model cells. Moreover, anti-miR-337-3p ameliorated si-circ-SPG11-mediated inhibition in ADAMTS5 mRNA and protein expression in OA model cells.ConclusionCirc-SPG11 facilitated OA development via regulating miR-337-3p/ADAMTS5 axis. This finding might contribute to the improvement of OA therapy.

Highlights

As a degenerative arthropathy, osteoarthritis (OA) extensively occurs in the aged including 10% males and 18% females [1]
Circ-SPG11 was upregulated in OA tissues and OA model cells
Circ-SPG11 was upregulated in OA tissues and OA model cells Due to a supply gap about researching the role of circSPG11 in OA, the expression of circ-SPG11 in OA tissues was primarily explored

Summary

Introduction

Osteoarthritis (OA) extensively occurs in the aged including 10% males and 18% females [1]. The irreversible OA progression eventually results in a loss of function of sufferers, imposes a heavy burden on mentality and physiology [2]. OA is characterized by the progressive damage in the structure and function of articular subassemblies, especially in cartilage [3]. The disequilibrium between anabolism and catabolism of extracellular matrix (ECM) is the main cause of cartilage damage, which further contributes to the deterioration of mechanical properties [4]. ECM degradation initially occurs in the surface of cartilage with the variation of matrix-degrading enzymes including collagenases metalloproteinases 13 (MMP13) and aggrecan-degrading enzymes (Aggrecan), and calcification in cartilage area gradually forms with the prolongation of degradation time [5]. The lack of research on the role of circRNA spastic paraplegia 11 (circ-SPG11) results in conducting this study

Methods

Results

Discussion

Conclusion