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Updated: Nov 1, 2025

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Circ-SPG11 knockdown hampers IL-1β-induced osteoarthritis progression via targeting miR-337-3p/ADAMTS5
Yongqiang Liu1, Qian Li1, Zhida Gao1
1Department of Orthopedics, Shijiazhuang People's Hospital, No. 365 Jianhua South Road, Shijiazhang, Hebei, 050000, People's Republic of China.
Background:
Osteoarthritis (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.
Methods:
The 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.
Results:
Circ-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.
Conclusion:
Circ-SPG11 facilitated OA development via regulating miR-337-3p/ADAMTS5 axis. This finding might contribute to the improvement of OA therapy.
Insights
Circular RNA spastic paraplegia 11 (circ-SPG11) promotes osteoarthritis (OA) by upregulating ADAMTS5 and downregulating microRNA-337-3p (miR-337-3p). Targeting this circRNA may offer new therapeutic strategies for OA.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Osteoarthritis (OA) is a leading cause of disability in the elderly.
- Circular RNAs (circRNAs) are implicated in various disease developments.
- The specific role of circRNA spastic paraplegia 11 (circ-SPG11) in OA remains under-investigated.
Purpose of the Study:
- To investigate the role and mechanism of circ-SPG11 in the development of osteoarthritis.
- To explore the relationship between circ-SPG11, microRNA-337-3p (miR-337-3p), and ADAMTS5 in OA.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect gene and protein expression.
- Cell viability, apoptosis, and inflammatory cytokine production were assessed using CCK-8, flow cytometry, and ELISA.
- Dual-luciferase reporter assays and RNA immunoprecipitation (RIP) were employed to verify molecular interactions.
Main Results:
- Circ-SPG11 and ADAMTS5 were upregulated, while miR-337-3p was downregulated in OA tissues and cells.
- Circ-SPG11 knockdown alleviated OA progression by reducing cell apoptosis and extracellular matrix (ECM) degradation.
- The miR-337-3p/ADAMTS5 axis was confirmed to be regulated by circ-SPG11, influencing OA pathogenesis.
Conclusions:
- Circ-SPG11 promotes osteoarthritis development through the regulation of the miR-337-3p/ADAMTS5 pathway.
- These findings suggest circ-SPG11 as a potential therapeutic target for improving OA treatment.
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