Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun;39(3):1099-1118.
doi: 10.1007/s10565-021-09665-2. Epub 2021 Oct 25.

MiR-337-3p confers protective effect on facet joint osteoarthritis by targeting SKP2 to inhibit DUSP1 ubiquitination and inactivate MAPK pathway

Shengsheng Jian  1 , Dixin Luo  2 , Yeyang Wang  2 , Wangyang Xu  2 , Hui Zhang  2 , Li Zhang  2 , Xiaozhong Zhou  3
Affiliations

MiR-337-3p confers protective effect on facet joint osteoarthritis by targeting SKP2 to inhibit DUSP1 ubiquitination and inactivate MAPK pathway

Shengsheng Jian et al. Cell Biol Toxicol. 2023 Jun.

Abstract

Objective: To probe the performance of miR-337-3p on the facet joint osteoarthritis (FJOA) and its underlying mechanism.

Methods: qRT-PCR and Western blot were utilized to analyze the levels of miR-337-3p and DUSP1 in the synovial tissues from 36 FJOA patients and 10 healthy controls. The human synovial fibroblasts of FJOA were isolated and cultured followed by cell transfection. Then, cells were exposed to 10 ng/mL of IL-1β to induce inflammatory response of synovial fibroblasts. The alternation on cell biological function in cell models was determined. The binding of miR-337-3p and SKP2 was predicted by StarBase, TargetScan, DIANA-microT and miRmap, and further verified by RIP assay and dual-luciferase reporter assay. Co-IP experiment and ubiquitination assay were used to display the binding of SKP2 and DUSP1 as well as the ubiquitination and degradation of DUSP1. After that, the FJOA rat model was established and miR-337-3p mimic or negative control was given to rats by tail vein injection. The pathological changes of synovial tissues, synovitis score, and inflammation level in rats were assessed.

Results: The low expressions of miR-337-3p and DUSP1 were noticed in the synovial tissues of FJOA patients and in IL-1β-induced synovial fibroblasts, and highly expressed p-p38 MAPK was noticed. Upregulation of miR-337-3p/DUSP1 or downregulation of SKP2 inhibited IL-1β-induced proliferation and inflammatory response of synovial fibroblasts. SKP2 was the target gene of miR-337-3p, and SKP2 induced the ubiquitination and degradation of DUSP1. MiR-337-3p exerted a protective effect on FJOA rats by alleviating damage of rat synovial tissues, promoting cell apoptosis and repressing inflammatory response.

Conclusion: MiR-337-3p plays a protective role in FJOA by negatively targeting SKP2 to suppress DUSP1 ubiquitination and inactivate the p38 MAPK pathway.

Keywords: DUSP1; Facet joint osteoarthritis; MiR-337-3p; SKP2; Ubiquitination; p38 MAPK.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Adam GO, Kim GB, Lee SJ, Lee H, Kang HS, Kim SJ. Red ginseng reduces inflammatory response via suppression MAPK/P38 signaling and p65 nuclear proteins translocation in rats and raw 264.7 Macrophage. Am J Chin Med. 2019;47(7):1589–609. https://doi.org/10.1142/S0192415X19500812 . - DOI - PubMed
    1. Arab HH, Salama SA, Abdelghany TM, Omar HA, Arafa EA, Alrobaian MM, et al. Camel milk attenuates rheumatoid arthritis via inhibition of mitogen activated protein kinase pathway. Cell Physiol Biochem. 2017;43(2):540–52. https://doi.org/10.1159/000480527 . - DOI - PubMed
    1. Asmamaw MD, Liu Y, Zheng YC, Shi XJ, Liu HM. Skp2 in the ubiquitin-proteasome system: a comprehensive review. Med Res Rev. 2020;40(5):1920–49. https://doi.org/10.1002/med.21675 . - DOI - PubMed
    1. Bhogaraju S, Kalayil S, Liu Y, Bonn F, Colby T, Matic I, et al. Phosphoribosylation of ubiquitin promotes serine ubiquitination and impairs conventional ubiquitination. Cell. 2016;167(6):1636–1649 e1613. https://doi.org/10.1016/j.cell.2016.11.019 . - DOI - PubMed
    1. Biver E, Berenbaum F, Valdes AM, Araujo de Carvalho I, Bindels LB, Brandi ML, et al. Gut microbiota and osteoarthritis management: an expert consensus of the European society for clinical and economic aspects of osteoporosis, osteoarthritis and musculoskeletal diseases (ESCEO). Ageing Res Rev. 2019;55:100946. https://doi.org/10.1016/j.arr.2019.100946 . - DOI - PubMed

Publication types

LinkOut - more resources